Scientia Pharmaceutica doi: 10.3390/scipharm94020037

Authors: Maksim E. Mironov Dmitry S. Baev Mohammad S. Hamad Sergey A. Borisov Vyacheslav I. Krasnov Tatyana V. Rybalova Maksim P. Pitukhin Irina V. Sorokina Tatyana G. Tolstikova Andrey G. Pokrovsky Anastasia I. Poltanovich Elvira E. Shults

Alkyn-1,2-diones have gained great attention as useful building blocks in organic synthesis. Regioselective synthetic routes towards 3,5-disubstituted isoxazoles, containing the methylfuroyl or diterpenylfuroyl moiety at the C-3 or C-5 position from alkyne-1,2-diones 1, 2, 3, are reported. The reaction with hydroxylamine hydrochloride 6 in ethanol afforded the 1,2-addition products: 5-aryl-3-(methylfuran-2-carbonyl)isoxazoles (yield 61–94%) or 16-(5-arylisoxazole-3-carbonyl)labdatrienes (yield 48–97%). The reaction of alkynediones 1–3 with 6 in THF in the presence of triethylamine led to 5-hydroxy-4,5-dihydroisoxazoles and subsequent dehydration afforded regioisomeric 3-aryl-5-(methylfuran-2-carbonyl)isoxazoles or 16-(3-arylisoxazole-5-carbonyl)labda-trienes (yield 65–98%). New heterocyclic compounds exhibited significant analgesic action in acetic acid writhing and hot-plate tests, and the activity was comparable to reference drugs diclofenac sodium and celecoxib. Isoxazoles, which possessed the most analgesic activity, reduced the concanavalin A-induced inflammation by 34–51%; the effect was comparable to the drug indomethacin. The results of in vitro biological assays (MTT test) revealed that isoxazoles were non-toxic against the normal epithelial VERO cells, and 16-(3-aryl-5-hydroxyisoxazoline-5-carbonyl)labdatrienes 20–24 exhibited selective cytotoxicity against the breast adenocarcinoma MCF 7 (GI50 = 4.7–8.3 μM) and cervical cancer cells C33 A (GI50 = 3.4–4.7 μM). Molecular docking analysis to determine the binding potential of new molecules to the active site of human COX-1 and COX-2 enzymes was conducted.

Scientia Pharmaceutica doi: 10.3390/scipharm94020036

Authors: Feiyun Wang Jing Hao Mengjie Li Yuying Zhu Jiange Zhang

Qin Bing eye drops, a traditional Chinese medicine-based in-hospital preparation, were historically indicated for the treatment of conjunctivitis, keratitis, and photokeratitis. This study aimed to develop Qin Pi extract (QP-E) using a proprietary extraction method, and to evaluate the therapeutic efficacy of QP-E alone, QP-E combined with Bing Pian (BP), and an ophthalmic formulation (QP-D) comprising both constituents in a preclinical model of dry eye disease (DED). DED was induced in mice via subcutaneous scopolamine administration alone, whereas a more robust dry eye phenotype was established in rats through combined treatment with scopolamine and environmental stressors. Ocular surface evaluation included measurement of tear secretion volume and corneal fluorescein staining scores. The results demonstrated that both QP-E monotherapy and the QP-E–BP combination significantly ameliorated key pathological features of DED, including tear film instability and corneal epithelial damage. QP-D—formulated with rationally optimized concentrations of QP-E and BP—significantly enhanced basal tear secretion and attenuated corneal epithelial injury in both murine and rat dry eye models. Mechanistic investigations revealed that QP-E treatment markedly inhibited VEGF-C secretion from classically activated (M1) macrophages, suppressed phosphorylation-dependent activation of the VEGF-C/VEGFR-3 signaling axis, and consequently impaired lymphatic endothelial cell migration and in vitro tube formation. These correlative findings indicate that QP-E may partially alleviate DED by suppressing lymphangiogenesis; however, direct causal evidence—such as genetic ablation of VEGF-C or pharmacological inhibition of VEGFR-3—was not established in the present study. Collectively, our data yield a testable mechanistic hypothesis and propose a novel therapeutic strategy targeting lymphatic remodeling for DED intervention.

Scientia Pharmaceutica doi: 10.3390/scipharm94020035

Authors: Adama Peña-Vera Sandra Dévora-Gutiérrez Chaxiraxi Morales Marrero Isabel V. Figueiredo Susana Abdala Kuri

Adverse Drug Reactions (ADRs) represent a major public health concern due to their impact on patient safety. In Spain, the Spanish Agency of Medicines and Medical Devices, through the FEDRA database, coordinates the reporting of suspected ADRs under real-world conditions of use, contributing to the continuous updating of safety information. In this context, community pharmacist, through Professional Pharmaceutical Care Services, plays a key role in the early detection of ADRs and Drug-Related Problems (DRPs). This article describes the case of a 70-year-old polymedicated woman included in a Personalized Dosage System (PDS). Following the substitution of diazepam with clonazepam and an increase in the dose of semaglutide, the patient developed urinary incontinence, nausea and abdominal pain. Coordinated intervention between the community pharmacy and primary care enabled adjustment of the clonazepam dose, optimization of semaglutide administration and discontinuation of unnecessary naproxen use. These measures resulted in improved treatment tolerance and safety, as well as optimization of pharmacotherapy.

Scientia Pharmaceutica doi: 10.3390/scipharm94020034

Authors: Akira Kageyama Takahiko Aoyama Rikuya Maehara Dai Harada Takashi Kawakubo Yasuhiro Tsuji

The usefulness of ChatGPT, a large language model, has recently been explored in medical research. However, no studies have examined its reproducibility or applicability to therapeutic drug monitoring (TDM), a core task of clinical pharmacists. In this simulation study, we evaluated the feasibility of using ChatGPT for vancomycin (VCM) TDM based on Bayesian estimation. A total of 1000 virtual patients were generated by Monte Carlo simulations using a population pharmacokinetic model of VCM. Bayesian-estimated pharmacokinetic parameters and predicted concentrations were input into ChatGPT, and dosage regimens were compared among the three conditions, using temperature as a hyperparameter (T = 0.1, 0.5, and 1.0). Reproducibility was evaluated using the mode percentage in repeated runs. The reproducibility of the ChatGPT output was higher at T = 0.1 than at T = 0.5 and T = 1.0. When ChatGPT simulated the mode-recommended regimen (T = 0.1), the target attainment rate of the area under the serum concentration (AUC) (400–600 mg·h/L) improved from 25.5% (pre-optimization AUC (fixed-dose regimen)) to 71.5% (post-optimization AUC (ChatGPT-guided regimen)). These findings demonstrate that ChatGPT-based TDM using Bayesian estimation can enhance dose optimization. Adjusting the hyperparameter temperature to 0.1 improved reproducibility, suggesting that a reliable ChatGPT-assisted TDM support system may be clinically useful.

Scientia Pharmaceutica doi: 10.3390/scipharm94020033

Authors: Valmik Sopan Aware Shreya Rajesh Rao Sanjay Pundalik Khairnar Arati Prabhu Hetal Abhay Shah Sonal M. Manohar

Background: Cancer is a leading cause of mortality worldwide. Discovery of small molecules as anticancer agents is an active area of research, as these molecules possess the remarkable ability to interact with specific targets within cancer cells. Objectives: In vitro anticancer activity of six hit derivatives from a series of 2-phenyl-substituted 4-amino–6, 7-dihydro-5H-cyclopenta[d]pyrimidines was tested against human cancer cell lines, viz., A549 (human lung cancer) and A431 (human skin cancer). Methods: Cytotoxicity was evaluated for six hits by the standard MTT assay. Further, their effect on clonogenic potential and cell cycle was tested using colony forming assay and flow cytometric analysis, respectively. Apoptosis-inducing potential was confirmed using Caspase-3/7 Glo assay and detection of cleaved caspase-3 by immunofluorescence. The effect on cell migration was tested using a wound healing assay. Target analysis, Molecular docking and ADMET simulations were performed to identify molecular targets, interactions and assess pharmacokinetic profiles. Results: Specific derivatives showed good to moderate cytotoxicity against A549 and A431 (with average IC50 in the range of ~30 µM), and these hits led to apoptosis and G1 arrest in these cell lines, respectively. Furthermore, identified hits inhibited cell migration in A549 cells. Computational consensus target analysis identified EGFR and CDK2 as high-confidence targets. Docking studies indicated favorable interactions and stability, whereas the ADMET analysis confirmed the drug-likeness and optimal pharmacokinetic and safety profiles of the small molecules. Conclusions: Our current study demonstrates the anticancer potential of novel pyrimidine derivatives. We envisage the use of these small molecules as promising anticancer agents, particularly in skin and non-small cell lung cancer.

Scientia Pharmaceutica doi: 10.3390/scipharm94020032

Authors: Sajib Chandra Roy Md. Jahid Hossain Uttom Kumar Sreedam Chandra Das Fatema Moni Deepankar Sutradhar Faria Tasneem A. S. M. Monjur Al Hossain

Improving the dissolution and solubility of poorly water-soluble drugs remains a major challenge in drug development. Solid dispersion (SD) techniques offer an effective strategy by which to enhance the bioavailability of BCS Class II drugs such as ivermectin (IVM). This study aimed to develop and validate stability-indicating analytical methods for the quantification of IVM and to evaluate the performance of the formulated SDs. A novel RP-HPLC and a UV spectrophotometric method were developed and validated in accordance with ICH guidelines. IVM SDs were prepared via physical mixing (PM), solvent evaporation (SE), and melt fusion (MF) using Poloxamer 188, Kollicoat® IR, and PEG 6000 at respective ratios of 1:1, 1:3, and 1:5. Dissolution studies showed a marked enhancement in drug release from SDs prepared by SE and MF methods compared with pure IVM. Among all formulations, the Poloxamer 188-based binary SD prepared by the SE method at a 1:5 ratio exhibited the highest dissolution (98.55% at 60 min), with release kinetics following anomalous (non-Fickian) transport (n = 0.681) according to the Korsmeyer–Peppas model. Solid-state characterization evidenced by FTIR, DSC, TGA, and SEM confirmed the transformation of IVM from its crystalline form to an amorphous state. Future studies will focus on the in vivo evaluation of the optimized IVM SD formulations.

Scientia Pharmaceutica doi: 10.3390/scipharm94020031

Authors: Regina Julieta Delgadillo Hernández Gregorio Guadalupe Carbajal Arízaga José Alfonso Cruz Ramos Rodolfo Hernández Gutiérrez José Armando Hernández Díaz Ana Alejandra Arias García Norma Morales-Hernández José Nabor Haro-González Zaira Yunuen García Carvajal Moisés Martínez Velázquez

This research aimed to develop glycerol–gelatin vaginal suppositories loaded with melatonin to enhance the localized effects of antineoplastic agents. The solubility of melatonin in different solvents was determined, and glycofurol, which is approved for pharmaceutical use, presented the highest solubilizing capacity. Furthermore, the cytotoxicity of melatonin incorporated into suppositories against HeLa cells was evaluated using MTT assays, individually and in combination with cisplatin. The results indicate that melatonin enhances the cytotoxic effects of cisplatin. The optimal formulation obtained from an experimental design was 33% gelatin, 1% PVA, 1% PEG 6000, 10% glycerol, 15% glycofurol, and 40% water. To ensure that the vaginal suppositories presented the necessary physical properties for optimal handling and application, tests were performed to determine weight uniformity, texture, surface features and disintegration time. Vaginal suppositories weighted around 1.43 g, showed Young’s modulus values of 7389.6 N/m2 and hardness around 1100 gf, and they disintegrated after 30 min at pH 4.2. Additionally, for in vitro melatonin release, FTIR and XRD tests confirmed the presence of melatonin in the formulation. It is concluded that the developed vaginal suppositories can be explored as potential vehicles for localized delivery of melatonin to the tumor site to enhance therapeutic outcomes.

Scientia Pharmaceutica doi: 10.3390/scipharm94020030

Authors: Maryna Stasevych Mykhailo Hoidyk Viktor Zvarych Andriy Karkhut Svyatoslav Polovkovych Roman Lesyk

The development of novel antiepileptic agents requires early identification of pharmacokinetic limitations to mitigate risks at later stages. This study aimed to perform in silico profiling of a library containing 448 novel 2H,5H-chromeno[4’,3’:4,5]thiopyrano[2,3-d]thiazol-2-one derivatives to select lead compounds with an optimal balance of safety and efficacy. The study was conducted using the ADMET-AI platform, based on a graph neural network, to predict physicochemical, pharmacokinetic, and toxicological properties. The methodology involved calculating drug-likeness descriptors for primary screening and a comparative statistical analysis of the top 20 selected structures against 16 approved antiepileptic drugs and four reference compounds. Based on drug-likeness descriptors and predicted ADMET (absorption, distribution, metabolism, excretion, toxicity) related parameters, 20 structures were prioritized for further analysis. Their predicted profiles suggested high intestinal absorption and blood–brain barrier (BBB) permeability, which may be relevant for central nervous system (CNS) directed agents. In comparison with the reference thiazolidinones, the prioritized compounds showed comparatively more favorable predicted mutagenicity and carcinogenicity profiles. Elevated predicted risks of hepatotoxicity and cardiotoxicity were observed for several structures, indicating the need for further structural optimization. The results suggest that the thiopyranothiazolidinone scaffold merits further anticonvulsant-oriented investigation at the stage of early compound prioritization. Experimental validation will be required to confirm the actual pharmacokinetic, toxicological, and anticonvulsant properties of the prioritized compounds.

Scientia Pharmaceutica doi: 10.3390/scipharm94020029

Authors: Rita I. L. Catarino Maria Fernanda C. Leal Adriana M. Pimenta Maria Renata S. Souto Francisco A. M. Silva

Taxanes, such as paclitaxel and docetaxel, are microtubule-stabilizing agents widely used in oncology, either as monotherapy or in combination regimens. While highly effective, these first-generation taxanes face important limitations, including significant toxicity, reduced water solubility, and the emergence of multidrug resistance. To address these challenges, semi-synthetic taxoids have been developed, aiming to improve pharmacological profiles and overcome therapeutic barriers. Central to these efforts is the understanding of structure-activity relationships, which guides the rational design of taxane analogues with enhanced efficacy and safety. This review explores recent advances in taxoid development, highlights findings from clinical trials, and evaluates how these new agents compare with traditional taxanes in terms of therapeutic potential and tolerability. While novel delivery systems offer improved outcomes with existing drugs, the development of new taxane analogues remains a promising approach to address drug resistance, albeit with challenges related to toxicity, high costs, and historically low success rates in drug development. Furthermore, taxanes are already used in certain cardiovascular conditions and show emerging potential in neurodegenerative diseases, although current evidence remains largely limited to preclinical or early-phase clinical studies. These developments mark an important evolution in the field and offer new opportunities for future therapeutic strategies.

Scientia Pharmaceutica doi: 10.3390/scipharm94020028

Authors: Samia Farhaj Omar Hamid Noman Ahmad Barbara R. Conway Muhammad Usman Ghori

Children are often underserved by adult-oriented oral medicines, leading to off-label use and dosage-form manipulation that may compromise dosing accuracy. This review summarises recent advances in paediatric orodispersible tablets (ODTs), focusing on manufacturing technologies, superdisintegrants, taste masking, and in vitro disintegration testing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance and a protocol registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (registration number INPLASY2025110022), we searched PubMed, EMBASE, MEDLINE, Scopus, and Google Scholar for experimental studies on paediatric-relevant ODT formulation and evaluation. Two reviewers screened studies and extracted data on manufacturing methods, excipients, disintegration/dissolution testing, and key outcomes. Risk of bias was assessed using a six-domain framework. Overall, 65 studies met the inclusion criteria for this review. Direct compression was the dominant method, with freeze-drying, sublimation, spray-drying, nanoparticle-in-tablet systems, and semi-solid extrusion/3D printing also reported. Crospovidone, croscarmellose sodium, and sodium starch glycolate were the most common superdisintegrants, while natural and co-processed disintegrants showed promise as cost-effective alternatives. Disintegration was usually assessed using pharmacopoeial methods, with some modified set-ups to better simulate oral conditions. Paediatric ODT development is advancing rapidly. Broader translation requires harmonised disintegration testing, age-stratified acceptability reporting, and GMP-ready workflows, alongside benchmarking of superdisintegrants and attention to dose flexibility, packaging, and affordability.

Scientia Pharmaceutica doi: 10.3390/scipharm94020027

Authors: Cecilia Guadalupe de Loza-García Ana Belem Rubio-García Salvador Hernández-Estrada Luis Alfonso Hernández-Villaseñor Luis Antonio Ramirez-Contreras Jorge Manuel Silva-Jara Jorge L. Mejía-Méndez Zuamí Villagrán Eugenio Sánchez-Arreola Napoleón González-Silva Luis Miguel Anaya-Esparza

Kalanchoe daigremontiana, a succulent herbaceous plant in the Crassulaceae family from Madagascar, has gained global popularity as an ornamental and medicinal species. This review examines the traditional uses, phytochemical composition, biological properties, toxicological aspects, and regulatory challenges of K. daigremontiana. The traditional medicinal uses of its leaves and roots include treating burns, rheumatic disorders, hypertension, diabetes, kidney pain, diarrhea, cough, fever, gastric issues, anxiety, inflammation, and cancer. Chemical compounds identified include phenolic acids, flavonoids, tannins, alkaloids, glycosides, saponins, sterols, terpenes, and fatty acids, with phenolic compounds and bufadienolides being predominant. In vitro studies of the crude extracts, bufadienolide-rich fractions, and isolated compounds have shown antioxidant, antibacterial, antifungal, antiviral, antiparasitic, anthelmintic, anti-inflammatory, anticoagulant, anti-aging, cytotoxic, antitumoral, and antiproliferative properties. In vivo studies have demonstrated hepatoprotective, skincare, and cardiac-glycoside-like effects. While crude extracts and bufadienolide-rich fractions have shown toxic effects in 2-week-old chicks, guinea pigs, and Artemia salina, no toxicity has been reported in goats, broiler chickens, laying hens, or human erythrocytes. Although K. daigremontiana-based products are commercially available as dietary supplements with various health claims, these lack scientific validation. Despite the potential pharmaceutical applications of K. daigremontiana, further research is needed to determine its effects, dosage, mechanisms, long-term safety, and side effects, with clinical studies essential to validate its therapeutic potential.

Scientia Pharmaceutica doi: 10.3390/scipharm94020026

Authors: Orlando Maia Barboza Luan Henrique Santos Barreto Felipe dos Santos Mendes Ivana Ferreira Simões Luís Filipe Gomes Santos Carlos Fernando da Silva Ferreira Luís Guilherme dos Santos de Sant’Anna Tainá Santos Lima Kaique Souza Santos de Jesus Saul Vislei Simões da Silva Victor Pena Ribeiro Silvia Lima Costa Gustavo Souza dos Santos Lourdes Cardoso de Souza Neta Aníbal de Freitas Santos Júnior

Quercetin, one of the most abundant flavonoids in nature, has attracted the attention of many researchers due to its chemical and biological properties. A series of metal–quercetin complexes (Cu2+, Co2+, Zn2+, Sn2+, Al3+, Cd2+ and Mg2+) were synthesized and systematically characterized by Fourier transform infrared spectroscopy (FTIR), UV-visible spectroscopy (UV–Vis) and nuclear magnetic resonance (NMR). These analyses confirmed that the complexes predominantly form through coordination with the 4-carbonyl group and adjacent phenolic hydroxyls. This induces measurable shifts in the ν(C=O), ν(O–H), and π→π* transition bands relative to free quercetin. The antioxidant capacity of the complexes was evaluated using 2,2-Diphenyl-1-Picrylhydrazyl (DPPH•) radical scavenging method, 2,2′-Azinobis(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS•)+ radical activity, and Ferric Reducing Antioxidant Power (FRAP) assay. Several complexes exhibited higher radical scavenging efficiency than quercetin, with inhibition percentages exceeding 80% in the DPPH• and ABTS•+ assays. Others showed reduced activity due to the masking of redox-active hydroxyl groups during metal coordination. FRAP results corroborated these trends, indicating metal-dependent modulation of reducing power. Antimicrobial evaluation revealed that selected complexes were more active than free quercetin, particularly against Staphylococcus aureus and Candida spp., with minimum inhibitory concentrations (MICs) ranging from 75–250 μg mL−1. Overall, metal complexation significantly alters the electronic structure and biological behavior of quercetin, highlighting the potential of metal–flavonoid complexes as multifunctional antioxidants and antimicrobials.

Scientia Pharmaceutica doi: 10.3390/scipharm94010025

Authors: Valentina Paganini Mariacristina Di Gangi Patrizia Chetoni Silvia Tampucci Daniela Monti Susi Burgalassi

Daily exposure to blue light emitted by digital devices has raised concerns about oxidative stress-mediated damage to the ocular surface. Despite growing interest, validated in vitro models to study blue light-induced oxidative stress in corneal epithelial cells remain limited. A reproducible in vitro method was developed using rabbit corneal epithelial (RCE) cells exposed to blue LED light (405 nm). Irradiation parameters were optimized to induce oxidative stress without causing overt cytotoxicity. Cellular viability, intracellular ROS production, and mitochondrial oxidative stress were assessed. The model was validated using reference antioxidants (ascorbic acid and oleuropein), oleuropein formulated in a drug-in-cyclodextrin-in-liposome system (OLE-DCL), and two commercial ophthalmic formulations applied before or after irradiation. Blue light irradiation at 4.57 W/m2 for 30 min significantly increased intracellular and mitochondrial ROS levels while preserving cell viability, indicating sublethal photo-oxidative stress. Ascorbic acid effectively suppressed ROS generation, whereas free oleuropein showed reduced efficacy, likely due to photosensitivity. OLE-DCL significantly enhanced antioxidant activity under irradiation. The model also discriminated between protective and restorative treatment strategies. This study establishes a validated in vitro blue light-induced oxidative stress model for corneal epithelial cells, suitable for screening antioxidant compounds, formulations, and application strategies relevant to ocular surface protection.

Scientia Pharmaceutica doi: 10.3390/scipharm94010024

Authors: José Jailson Lima Bezerra Mateus Araújo da Luz Aline Peres Ferreira Joseilton Franco França Tatiana Porto Santos Anderson Angel Vieira Pinheiro Maria da Conceição de Menezes Torres

Globally, breast cancer is one of the most prevalent tumors in women and remains a major concern due to its high mortality rate. Although treatment options for this disease have evolved over the years, there are still many cases of recurrence and metastasis. In this context, considering the importance of evaluating less aggressive and more efficient therapeutic alternatives to aid in the treatment of breast cancer, the present study critically discusses the cytotoxic effects of diterpenoids isolated from Croton species (Euphorbiaceae). The articles were retrieved from different databases, from the first report published in 2005 to October 2025. A total of 115 diterpenoids were isolated from 15 Croton species and investigated against different breast cancer cell lines (MDA-MB-231, MCF-7, and MDA-MB-468). These compounds mainly belong to the kaurane group (40%), followed by clerodane (14%), tigliane (12%), and abietane (10%). Of this total, only 25 compounds showed promising results (IC50 = < 10 µM). The mechanisms of action of the compounds crokokaugenoid A, kongensin A, kongensin D, ent-16β,17α-dihydroxykaurane, and lauicyclone A have been reported. These compounds likely act by inducing apoptosis, autophagy, cell cycle arrest, inhibition of cell migration and invasion, and DNA fragmentation in breast cancer cell lines. To date, no randomized clinical trials have been conducted using Croton diterpenoids for the treatment of breast cancer. Therefore, further studies on the modulation of the immune response by these natural products are essential to better understand their immunotherapeutic activity in the tumor microenvironment during breast cancer progression.

Scientia Pharmaceutica doi: 10.3390/scipharm94010023

Authors: Katherine González-Berrio Miguel Ángel Puertas-Mejía

Brown algae are a valuable source of bioactive secondary metabolites, particularly polyphenols and sulfated polysaccharides with photoprotective and antioxidant activities. Among them, fucoidan stands out for its biocompatibility, biodegradability, and demonstrated photoprotective effects, mainly through antioxidant and anti-photoaging properties, making it a promising natural component for UV-protective formulations. This study developed polyelectrolyte complex sub-micron particles based on fucoidan and chitosan (F/Cs) to encapsulate quercetin (Q) as a natural UV-active antioxidant. Fucoidan from Sargassum filipendula was extracted and fractionated by ultrafiltration. An RCBD was used to optimize pH and F/Cs mass ratio. The optimal blank formulation (F/Cs = 1:1, pH 5.0) yielded sub-micron colloidal carriers with a mean hydrodynamic diameter of 421 ± 23 nm (PDI 0.252 ± 0.059) with ζ = +43.5 ± 1.6 mV. Quercetin-loaded particles (F/Cs/Q = 1:1:0.5) presented 915 ± 87 nm (PDI 0.278 ± 0.093) and ζ = +54.6 ± 1.2 mV. UV–Vis spectra evidenced UVB and partial UVA absorption for fucoidan and broad UVA/UVB coverage for quercetin, preserved upon encapsulation. Antioxidant activity was retained post-encapsulation (EC50, DPPH: 0.094 mg/mL; ABTS: 0.0749 mg/mL). These results demonstrate the potential of fucoidan–chitosan colloidal systems as multifunctional, biodegradable carriers for natural photoprotective agents, supporting their application in next-generation dermatological and cosmeceutical formulations.

Scientia Pharmaceutica doi: 10.3390/scipharm94010022

Authors: Yoana Sotirova

Jojoba oil is a well-established skin-beneficial liquid wax with high value in topical formulations. Bigels, as preferred semi-solid dosage forms, serve as versatile platforms by incorporating hydrogels and oleogels to leverage their advantages and address their limitations. In this study, jojoba oil bigels were developed using sorbitan monostearate (20%, w/w) as an oleogelator and different hydrophilic bases, 1% Carbomer 940, 6% methylcellulose, or 20% Poloxamer 407 gel, with all concentrations expressed relative to the corresponding phase. Nine bigels were obtained by varying hydrogel-to-oleogel ratios (90:10–70:30). They were evaluated in terms of their organoleptic, microstructural, and textural characteristics. Both the hydrogel matrix type and the phase proportion impacted the studied properties. Carbomer bigels displayed the highest spreadability, methylcellulose formulations showed the greatest adhesiveness, and poloxamer systems exhibited maximum firmness and cohesiveness, with a comparatively more homogeneous phase distribution. The increase in oleogel content enhanced firmness and cohesiveness while modulating spreadability and adhesiveness in a hydrogel-dependent manner. Moreover, all designed formulations remained physically stable after centrifugation, but only those containing 80% carbomer gel or 70% or 80% poloxamer gel preserved their mechanical characteristics without significant changes after freeze-thawing. Besides identifying three promising biphasic dermal drug delivery platforms, these findings reinforce the tunability of bigels through the careful component selection.

Scientia Pharmaceutica doi: 10.3390/scipharm94010021

Authors: Héctor Iván Saldívar-Cerón

Once-monthly injectable therapies targeting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and adjacent metabolic pathways are moving from a conceptual goal to a plausible next step for type 2 diabetes (T2D) and obesity. The most clinically advanced program is maridebart cafraglutide (MariTide), a long-acting GLP-1 receptor agonist conjugated to an Fc-containing scaffold that also mediates sustained GIP receptor antagonism. Across phase 2 trials, once-monthly maridebart has produced clinically meaningful weight loss (~12–16% in adults without diabetes; ~8–12% in those with T2D), together with HbA1c reductions of ~1.2–1.6 percentage points, with a safety profile broadly consistent with GLP-1-based therapy. An exploratory every-8-weeks regimen showed attenuated efficacy, suggesting that monthly dosing may represent a practical lower boundary for maintaining therapeutic exposure and metabolic effect in this format. Beyond maridebart, a rapidly expanding pipeline—including ultra-long-acting GLP-1 analogs, dual GLP-1/GIP agonists, long-acting GIPR antagonists, amylin receptor agonists, and emerging thyroid hormone receptor beta (THRβ) agonists—is actively testing monthly regimens or induction-to-monthly maintenance strategies; however, most readouts remain early and are frequently limited to conference presentations or sponsor communications. Accordingly, much of the pipeline evidence should be interpreted as early-phase and non-peer-reviewed, and therefore hypothesis-generating. Key uncertainties include long-term durability, cardiometabolic outcomes, immunogenicity, and interindividual variability in response, which will ultimately determine how once-monthly regimens integrate with established weekly standards in routine care.

Scientia Pharmaceutica doi: 10.3390/scipharm94010020

Authors: Sophia S. Borisevich Edward M. Khamitov Gulshat A. Masyagutova Olga I. Yarovaya Sergey L. Khursan

A comprehensive MD + QC methodology was developed and applied to evaluate various aspects of Arbidol interactions with functional amino acids of surface proteins of influenza virus and SARS-CoV-2. The spatial structure, solvation features, conformational behavior of Arb AA (AA–Trp, Tyr, Phe, and Val) complexes were established, and the statistics of intermolecular interactions in the complex were described. It was found that Arb can participate in strong and long-lived π-π stacking interactions with aromatic amino acids. The binding energy (BE) of Arbidol and amino acids in aqueous solution was estimated using an explicit solvation model, QTAIM analysis and correlation of BE vs. total electron density at the bond critical points of the complex. Theoretical calculations were validated by experimental studies of fluorescence (FL) quenching of aromatic AA by Arbidol. Spectral-fluorescent properties of Arbidol hydrochloride in aqueous solutions were studied, and the luminescence quantum yield for the electronically excited state of Arb was determined.

Scientia Pharmaceutica doi: 10.3390/scipharm94010019

Authors: Christophor Lazov Krassimira Yoncheva Marta Slavkova

Lipid nanoparticles have been a subject of intense scientific interest in recent years due to their inherent biocompatibility, versatile delivery routes, drug loading and potential large-scale production. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are matrix lipid nanoparticles that differ in their lipid composition and, specifically, the presence of liquid lipid in the latter. Their production is straightforward and relatively inexpensive. They provide an additional specific advantage for dermal delivery in the treatment of atopic dermatitis, as they can carry various drugs and even ameliorate the skin condition on their own. The chronic character and the observed predominance of atopic dermatitis in the pediatric population further justify the utility of improved therapeutic strategies and the application of SLNs and NLCs specifically. Therefore, in the current review, we aimed to systematically collect the available literature on this topic and to evaluate where we stand in terms of scientific and practical knowledge. The observations show significant potential for clinical translation for both SLNs and NLCs in the near future. However, some key limitations were identified and discussed. The novelty of this review lies in its systematic consolidation and critical discussion of SLNs and NLCs specifically in the context of atopic dermatitis.

Scientia Pharmaceutica doi: 10.3390/scipharm94010018

Authors: Jorge L. Gutierrez-Pajares Isabel Gómez-Betancur Francisco León

Cobalamin, also known as vitamin B12, is an essential cofactor involved in one-carbon metabolism, mitochondrial function, and epigenetic regulation. As humans rely entirely on dietary intake of cobalamin paired with a highly coordinated absorption and transportation system, disruptions to this metabolic process can have profound health consequences. Breast cancer, the most frequently diagnosed malignancy among women worldwide, exhibits distinct metabolic adaptations, including altered cobalamin uptake and dependency on B12-driven biochemical pathways. This review summarizes the molecular mechanisms governing cobalamin metabolism, with a focus on absorption, transport, and intracellular processes relevant to breast cancer biology. We then examine how breast cancer cells reprogram these pathways. Finally, we evaluate emerging pharmaceutical strategies that target cobalamin metabolism, including B12-based imaging probes, cobalamin-conjugated drug delivery systems, and inhibitors of B12-dependent enzymes. Although these approaches show promise, further research is needed to define subtype-specific metabolic signatures, optimize cobalamin-mediated drug targeting, and clarify how systemic B12 status influences therapeutic response. By integrating biochemical, epidemiological, and translational perspectives, this review outlines how cobalamin-centered strategies may contribute to more precise diagnostic and therapeutic options for breast cancer.

Scientia Pharmaceutica doi: 10.3390/scipharm94010017

Authors: Ana María Sepúlveda Marcela Manrique-Moreno Sofía Echeverri-Gaviria Gloria A. Santa-González

Triple-negative breast cancer is the subtype with the worst prognosis and has limited treatment options. Bioactive peptides are a promising alternative, having demonstrated antitumor properties with a mechanism of action involving the cell membrane. In this study, we evaluated the Ctn-2 peptide, a fragment of crotalicidin (Ctn), which has shown antitumor activity with highly lytic characteristics but is not selective in non-tumor cells. We evaluated the antitumor activity of the peptide Ctn-2 in triple-negative breast cancer cells and its selectivity over non-tumoral cells. Comparative analyses with LTX-315 and biophysical studies on model membranes indicate that Ctn-2 preferentially interacts with cancer-associated lipids. Functional assays further show that its action involves controlled membrane disruption and associated cellular responses. We also examined the combined effect of Ctn-2 and doxorubicin, finding that Ctn-2 selectively enhanced cytotoxicity in tumor cells and potentiated the activity of conventional chemotherapy. Overall, the results indicate that Ctn-2 is a membrane-active peptide with selective antitumor potential and the ability to improve chemotherapeutic efficacy.

Scientia Pharmaceutica doi: 10.3390/scipharm94010016

Authors: Malika Mekhalfi Sabine Berteina-Raboin

Mucuna pruriens (M. pruriens) is a legume that attracts researchers for its benefits and has been used for centuries in Ayurvedic medicine. While its effectiveness has long been recognized, in-depth studies have shown that its activity is mainly due to its high levodopa (L-Dopa) content, but not exclusively. It also contains other structures that can improve its effectiveness and reduce the side effects encountered when using synthetic L-Dopa. Similarly, other molecules that selectively inhibit certain enzymes are present. Various methods of varying effectiveness have been used to extract the active ingredients, and recently, progress has been made in extraction methods. Clinical studies already exist demonstrating its therapeutic benefits, similar to those of synthetic L-Dopa, for several conditions, and showing the limitations of certain side effects such as dyskinesias. Further studies and clinical trials are still needed, but this plant could be a very good alternative in countries that do not have or no longer have access to certain drugs. This legume can be grown without difficulty in these countries, as it has the advantage of being resistant to drastic climatic conditions.

Scientia Pharmaceutica doi: 10.3390/scipharm94010015

Authors: Antoniy A. Kladiev Elena V. Uspenskaya Mikhail G. Baryshev Vasilii A. Ivlev Vasilii G. Vasil’ev Samvel S. Barsegyan Ainaz Safdari

The clinical efficacy of chemotherapy against rapidly proliferating cells stimulates both the development of new agents and the reassessment of established drugs. Spectroscopic methods (UV, FT-IR, and 1H NMR) were applied to characterize prospidium chloride and related substances. The FT-IR spectrum of prospidium chloride, arising from vibrational transitions within the alkyl fragments of the dispirotripiperazinium cation, is reported with band assignments. Electronic transitions between molecular orbitals are analyzed using quantum–mechanical selection rules (Laporte and spin selection rules). The n→σ* transition (ΔS = 0) corresponds to the absorption maximum at λmax = 282 ± 0.40 nm (ε = 3.89 ± 0.08 L·mol−1·cm−1). A 1H NMR spectrum (700 MHz) was used to assign chemical shifts δ (ppm), J-coupling constants (Hz), and gauche conformational features of prospidium chloride and its dihydroxy and epoxy impurities. Quantitative 1H NMR (qNMR) was applied to determine the content of the active pharmaceutical ingredient and related substances. The methods provide complementary structural information for the characterization of prospidium chloride.

Scientia Pharmaceutica doi: 10.3390/scipharm94010014

Authors: Nerlis Pájaro-Castro Paulina Valenzuela-Hormazábal Erick Díaz-Morales Kenia Hoyos Karina Caballero-Gallardo David Ramírez

Pseudomonas aeruginosa is a Gram-negative pathogen with a remarkable capacity to acquire multiple resistance mechanisms, severely limiting current therapeutic options. Consequently, the identification of new antimicrobial agents remains a critical priority. In this study, an integrated in silico-guided strategy was applied to identify small molecules with antibacterial potential against P. aeruginosa, targeting the quorum-sensing regulator LasR (PDB ID: 2UV0) and elastase (PDB ID: 1U4G). Pharmacophore modeling was performed for both targets, followed by ligand-based virtual screening, structure-based virtual screening (SBVS), and MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) binding free energy calculations. Top-ranked compounds based on predicted binding affinity were selected for in vitro cytotoxicity and antibacterial evaluation. Antimicrobial activity was assessed against three P. aeruginosa strains: an American Type Culture Collection (ATCC) reference strain, a clinically susceptible isolate, and an extensively drug-resistant (XDR) clinical isolate. SBVS yielded docking scores ranging from −6.96 to −12.256 kcal/mol, with MM-GBSA binding free energies between −18.554 and −88.00 kcal/mol. Minimum inhibitory concentration (MIC) assays revealed that MolPort-001-974-907, MolPort-002-099-073, MolPort-008-336-135, and MolPort-008-339-179 exhibited MIC values of 62.5 µg/mL against the ATCC strain, indicating weak-to-moderate antibacterial activity consistent with early-stage hit compounds. MolPort-008-336-135 showed the most favorable activity against the clinically susceptible isolate, with an MIC of 62.5 µg/mL, while maintaining HepG2 cell viability above 70% at this concentration and an half-maximal inhibitory concentration (IC50) greater than 500 µg/mL. In contrast, all tested compounds displayed MIC values above 62.5 µg/mL against the XDR isolate, reflecting limited efficacy against highly resistant strains. Overall, these results demonstrate the utility of in silico-driven approaches for the identification of antibacterial hit compounds targeting LasR and elastase, while highlighting the need for structure–activity relationship optimization to improve potency, selectivity, and activity against multidrug-resistant P. aeruginosa.

Scientia Pharmaceutica doi: 10.3390/scipharm94010013

Authors: Karina Kleinfelder Paola Lecca Roberta Valeria Latorre Chiara Mortali Sara Casati Sofia Vanerio Claudio Sorio Paola Melotti

Pharmacological modulators of CFTR have significantly changed the cystic fibrosis (CF) phenotype of subjects affected by this multi-organ disease. Here, we evaluated the CFTR function analysis (short-circuit chamber in colonoids) in response to Elexacaftor/Tezacaftor/Ivacaftor (ETI) with the clinical benefits of in vivo treatment with ETI in ten CF subjects. We found that the functional response of ETI-corrected PDROS significantly correlated with the absolute change in the sweat chloride test. Thus, our work reinforces the use of organoid-derived human intestinal monolayers to guide clinicians in selecting CFTR-targeted therapies.

Scientia Pharmaceutica doi: 10.3390/scipharm94010012

Authors: Seon-Hyeok Kim Se Jeong Kim Eun Ji Ko Hae Ran Lee Seong Min Hong Se Hwan Ryu Dae Hee Lee Young Guk Kim Jeong Yun Yu Jae Kang Lee Mi Kyeong Lee Sun Yeou Kim

Alzheimer’s disease and related neurodegenerative disorders are associated with progressive cognitive decline, primarily driven by cholinergic dysfunction and impaired synaptic signaling. Hericium erinaceus, also known as lion’s mane mushroom, has been reported to promote neuronal differentiation and synaptic plasticity. In this study, a standardized H. erinaceus extract powder (HEP) was prepared from fruiting bodies and quantified using hericene A as a marker compound. The neuroprotective effects of HEP were then evaluated in both cellular and animal models of scopolamine-induced cognitive dysfunction. Pretreatment of SH-SY5Y human neuroblastoma cells with HEP (5–25 μg/mL) significantly improved cell viability and reduced scopolamine-induced apoptosis, while enhancing the activation of neuroplasticity-related signaling proteins, including brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and extracellular signal-regulated kinase (ERK). In vivo, oral administration of HEP (300 mg/kg) to scopolamine-treated ICR mice markedly improved cognitive performance, increasing the recognition index to 63.8% compared with 41.6% in the scopolamine group, and enhancing spontaneous alternation in the Y-maze test to 59.6%. These cognitive improvements were accompanied by preserved hippocampal neuronal structure and increased BDNF immunoreactivity. Additionally, HEP improved cholinergic function by restoring serum acetylcholine levels and reducing acetylcholinesterase activity. Collectively, these findings suggest that standardized HEP exerts neuroprotective and cognition-enhancing effects via modulation of cholinergic markers and activation of BDNF-mediated neuroplasticity, highlighting its potential as a functional food ingredient or nutraceutical for preventing cognitive decline related to cholinergic dysfunction.

Scientia Pharmaceutica doi: 10.3390/scipharm94010011

Authors: Sreenivas Avula Satish Koppireddi Micky D. Tortorella Cleopatra Neagoie

This study reports the exclusive and rapid synthesis of twenty-four derivatives of 1-((mono/bis)trifluoromethyl)phenyl-3-(4-arylthiazol-2-yl)thioureas (series 7, 9 and 11), along with their antimicrobial activities against Candida albicans, Mycobacterium smegmatis and seven additional bacterial strains. The anticancer potential of these compounds was evaluated against various human cancer cell lines, including A549 (lung adenocarcinoma), HeLa (cervical carcinoma), IMR32 (neuroblastoma), MCF-7 (breast adenocarcinoma), HCT116 (colon cancer) and DU145 (prostate cancer). Among these, 1-(3,5-bistrifluoromethylphenyl)-3-(thiazol-2-yl)thiourea (7i) and 1-(4-trifluoromethylphenyl)-3-(4-(3-chlorophenyl)thiazol-2-yl)thiourea (11h) demonstrated significant antimicrobial activity against M. luteus, S. aureus, S. aureus 1 and C. albicans. Additionally, 1-(4-(3-chlorophenyl)thiazol-2-yl)-3-(3-trifluoromethylphenyl)thiourea (9g) and 1-(4-trifluoromethylphenyl)-3-(4-(2-fluorophenyl)thiazol-2-yl)thiourea (11g) showed activity against Mycobacterium smegmatis. The bioassay tests indicated that many of the thiourea derivatives exhibited moderate activity against the A549, HeLa, MCF-7 and HCT116 cancer cell lines.

Scientia Pharmaceutica doi: 10.3390/scipharm94010010

Authors: Tibor Rák Edit Ormai Györgyi Horváth

Mental health disorders, particularly anxiety and insomnia, are increasingly prevalent worldwide, prompting interest in herbal-based complementary therapies. This study surveyed 168 Hungarian healthcare professionals to evaluate their knowledge and recommendations regarding herbal sedatives and analyzed seven commonly suggested OTC products available in Hungary, using thin-layer chromatography (TLC) and UV–Vis spectrophotometry according to the European Pharmacopoeia. The survey revealed that 86.9% of respondents recommend herbal products for nervous system complaints, with Valeriana officinalis and Melissa officinalis being the preferred ingredients. Herbal teas and traditional herbal medicines were the most frequently suggested product categories. Laboratory analysis confirmed the presence of marker compounds in all tested products; however, significant variability in active ingredient concentrations was observed. One homeopathic product contained an unidentified alkaloid-like compound, raising safety concerns. Essential oil yields from tea mixtures also varied markedly, and some products did not meet pharmacopoeial standards for hypericin content. These findings highlight the popularity of phytotherapy among healthcare professionals and the need for stricter quality control of OTC herbal sedatives. Future research should include multi-batch analyses and clinical trials to establish robust evidence for efficacy and safety.

Scientia Pharmaceutica doi: 10.3390/scipharm94010009

Authors: Jesus Magdiel García-Díaz Asbiel Felipe Garibaldi-Ríos Martha Patricia Gallegos-Arreola Filiberto Gutiérrez-Gutiérrez Jorge Iván Delgado-Saucedo Moisés Martínez-Velázquez Ana María Puebla-Pérez

Drug discovery is a complex and expensive process in which only a small proportion of candidate molecules reach clinical approval. Computational methods, particularly computer-aided drug design (CADD), have become fundamental to accelerate and optimize early stages of discovery by integrating chemical, biological, and pharmacokinetic information into predictive models. This review outlines a complete computational workflow for chemical compound analysis, covering molecular structure generation, database selection, evaluation of absorption, distribution, metabolism, excretion and toxicity (ADMET), target prediction, and molecular docking. It focuses on freely accessible and web-based tools that enable reproducible, cost-effective, and scalable in silico studies. Key platforms such as PubChem, ChEMBL, RDKit, SwissADME, TargetNet, and SwissDock are highlighted as examples of how different resources can be integrated to support rational compound design and prioritization. The article also discusses essential methodological principles, data curation strategies, and common limitations in virtual screening and docking analyses. Finally, it explores future directions in computational drug discovery, including the incorporation of artificial intelligence, multi-omics integration, and quantum simulations, to enhance predictive accuracy and translational relevance.

Scientia Pharmaceutica doi: 10.3390/scipharm94010008

Authors: Aida Lahmar Balkis Abdelaziz Nahla Gouader Abir Salek Imen Waer Leila Chekir Ghedira

Ultraviolet B radiation is a major cause of skin aging, cellular senescence, and inflammaging, mediated by the excessive production of reactive oxygen species (ROS) and induction of apoptosis. This study evaluated the photo-protective effects of astaxanthin, one of the strongest natural antioxidants, in UVB-treated keratinocytes. The antioxidant capacity of astaxanthin was evaluated using ABTS, DPPH, and NBT/riboflavin/SOD assays. HaCaT cells were exposed to 30 mJ/cm2 of UVB radiation. Photoprotective effects and accumulated ROS were evaluated in UVB-irradiated HaCaT cells by MTT and DCFH-DA assays. Nitric oxide levels were quantified using the Griess reagent. Apoptosis was assessed by dual staining using acridine orange/ethidium bromide, lysosomal integrity by acridine orange uptake, and cell migration by scratch assay. Cell adhesion was assessed on ECM-coated Nunc plates. Finally, we formulated a 0.5% astaxanthin-enriched cream. Astaxanthin mitigated UVB-induced damage by reducing intracellular ROS levels by 3.7-fold, decreasing nitric oxide production to 29.8 ± 7.7% at the highest concentration, and maintaining lysosomal integrity. The carotenoid significantly enhanced cell viability, increasing it from 60.64 ± 8.3% in UV-treated cells to 102.1 ± 3.22% at 40 µM. Moreover, treated cells showed a significant reduction (p < 0.001) in the apoptotic rate (37.7 ± 3.1 vs. 87.7 ± 3.8 in UVB-irradiated cells, as evidenced by reduced chromatin condensation and nuclear fragmentation. Astaxanthin also enhanced tissue repair, as evidenced by increased cell migration and adhesion to several extracellular matrix (ECM) proteins (poly-L-lysine, laminin, fibrinogen, vitronectin and collagen I). In silico molecular docking predicted strong binding affinities between astaxanthin and key cellular targets, including JAK2 (−9.9 kcal/mol, highest affinity), STAT3, FAK, COX-2, NF-k-B, MMP2, and MMP9. The formulated cream demonstrated an in vitro SPF of 7.2 ± 2.5. Astaxanthin acts as a multifunctional photoprotective compound, providing a strong rationale for its incorporation into cosmetic and dermatological formulations, as further supported by the successful formulation and in vitro SPF estimation of an astaxanthin-enriched cream.

Scientia Pharmaceutica doi: 10.3390/scipharm94010007

Authors: Mateo Pérez-R G. Orozco A. González-Ruiz Miriam V. Flores-Merino

The synthesis of sodium carboxymethylcellulose (NaCMC) from lignocellulosic pineapple stubble provides a renewable alternative to conventional cellulose sources for pharmaceutical applications. This study aimed to obtain NaCMC from pineapple biomass, characterize it according to pharmacopoeial specifications, and formulate hydrogels as a physicochemical proof-of-concept for future drug delivery and tissue regeneration applications. NaCMC was successfully synthesized and met the requirements of the Mexican Pharmacopoeia. Hydrogels were prepared by blending NaCMC with gelatin and crosslinking with citric acid. Spectroscopic, morphological, and thermal analyses confirmed the structural equivalence between pineapple-derived NaCMC (NaCMC-Pi) and commercial NaCMC (NaCMC-Co). Swelling and gel fraction studies showed that NaCMC-Pi hydrogels exhibited a higher gel fraction, indicating a more crosslinked network, which corresponded to lower swelling capacity but higher thermal stability compared to NaCMC-Co hydrogels. Overall, these results demonstrate that pineapple stubble is a viable source of pharmaceutical-grade NaCMC and that the resulting hydrogels provide a robust physicochemical basis for future biomedical validation. The use of agro-industrial residues additionally offers a complementary sustainability benefit without compromising pharmaceutical performance.

Scientia Pharmaceutica doi: 10.3390/scipharm94010006

Authors: Pratikshya Paudel Prabir Kumar Gharai

Neurodegeneration—driven by oxidative stress, chronic inflammation, and protein aggregation—underlies disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and stroke. Current pharmacological treatments are largely symptomatic and do not restore lost neural circuitry, motivating regenerative approaches. Mesenchymal stem cells (MSCs) provide neurotrophic and immunomodulatory benefits and can support synaptic repair, yet robust conversion into mature, electrophysiologically functional neurons remain challenging and often depends on complex inducer cocktails with translational limitations. Crocin, a saffron-derived carotenoid, is reported to enhance neurogenesis and neuroprotection in preclinical models through pathways including Wnt/β-catenin, Notch1, CREB/BDNF, and modulation of GSK-3β, while reducing apoptosis and inflammatory signaling. Here, we synthesize evidence supporting crocin’s neuroprotective and proneurogenic activity and propose a testable hypothesis that crocin-based or crocin-modified formulations could be evaluated as adjuncts to guide MSC neuronal lineage commitment. Importantly, direct evidence that crocin alone can drive MSC trans-differentiation into fully functional neurons is currently insufficient; future work should define functional benchmarks (electrophysiology, synaptogenesis, and phenotypic stability) and rigorously validate safety, dosing, and delivery strategies for neuroregenerative translation.

Scientia Pharmaceutica doi: 10.3390/scipharm94010005

Authors: Oleksandra Havrylenko Yuliya Kondratova Kateryna Typlynska Liliya Logoyda

The main goal of this study was to develop methods for quality control of naftifine hydrochloride in solution and cream forms, focusing on “Quantitative Determination” and “Related Impurities.” New, precise, accurate, and environmentally friendly high performance liquid chromatography (HPLC) methods were developed for the determination of naftifine hydrochloride and its impurities. “Quantitative determination” was performed using a diode array detector at 254 nm with an isocratic mobile phase (1.154 g of ammonium acetate R dissolved in 300 mL of water R, followed by the addition of 0.2 mL of glacial acetic acid R, mixed well) and methanol (30:70). The chromatographic columns Gemini C18 and Luna C18 were used. “Related impurities” were separated at 270 nm using a gradient mobile phase consisting of 10 M sodium octanesulfonate, 0.4 g/L disodium hydrogen phosphate anhydrous solution (pH 6.5), acetonitrile, and the Synergi Hydro-RP chromatographic column. The developed method, validated according to ICH guidelines, showed run times of 55 min for impurity analysis and 6 min for active ingredient determination. The methods were successfully applied to the quality control of the solution and cream.

Scientia Pharmaceutica doi: 10.3390/scipharm94010004

Authors: Edwin Y. Valladares Chávez Luis A. Moreno-Rocha Lucia Ortega Cabello Ponciano García-Gutiérrez Jorge E. Miranda-Calderón

The accurate determination and quantification of praziquantel are essential for optimizing its therapeutic effectiveness in treating schistosomiasis and neurocysticercosis, two significantly neglected tropical diseases. Its challenging physicochemical profile, extensive metabolism, and stereochemical complexity requires robust analytical methods for reliable quantification in clinical, veterinary, and pharmaceutical samples. This review provides a comprehensive and critical evaluation of analytical strategies used for PZQ determination, spanning fluorometric and radiometric assays, HPLC–UV, LC–MS, LC–MS/MS, and enantioselective chromatographic approaches. Particular emphasis is placed on the evolution toward highly sensitive LC–MS/MS methods and their alignment with contemporary regulatory expectations, including ICH M10 requirements. These advancements have significantly improved sensitivity, specificity, and reproducibility, which are crucial for pharmacokinetic, pharmacodynamic, and bioequivalence studies. Enantioselective methods for distinguishing PZQ enantiomers and metabolites are discussed. The aim of these innovations is to increase praziquantel bioavailability, improve patient adherence, and support its continued use in mass drug administration programs. Finally, the review highlights implementation challenges in resource-limited settings and proposes analytical models to expand global bioanalytical capacity. Together, these insights provide a structured foundation for selecting and developing high-quality, regulatory-compliant analytical methods for PZQ.

Scientia Pharmaceutica doi: 10.3390/scipharm94010003

Authors: Eneida Azaret Montaño-Grijalva Francisco Rodríguez-Félix José Agustín Tapia-Hernández Enrique Márquez-Ríos Carmen Lizette Del-Toro-Sánchez Dora Evelia Rodríguez-Félix Ricardo Nalda-Molina Elizabeth Carvajal-Millan Carlos Gregorio Barreras-Urbina Itzel Yanira López-Peña Cielo Estefanía Figueroa-Enríquez

Currently, there are various approaches to the treatment of diabetes. Regarding type 2 diabetes (T2D), treatment focuses on blood glucose control. When changes in lifestyle do not achieve this glycemic control, the option is to start therapy with antidiabetic drugs such as metformin. However, long-term metformin use causes disturbances that may affect treatment approaches. This review examines recent advances in nanotechnology that have developed new forms of drug administration that can improve the efficacy of the treatment, where nanomaterials, nanostructures, and nanoparticle design are involved, so that they provide controlled and gradual release. The use of biopolymers (as drug delivery systems) has ensured biocompatibility, biodegradability, and low toxicity. There are several methods for obtaining a drug delivery system, including electrospinning, electrospraying, nanoprecipitation, etc. These systems improve drug delivery and can be used orally, transdermally, or intravenously, among means of administration. This review describes the new forms of the administration of metformin in the treatment of T2D, based on the encapsulation of metformin in polymeric matrices such as proteins, polysaccharides, and lipids, among others.

Scientia Pharmaceutica doi: 10.3390/scipharm94010002

Authors: Gleb Vladimirovich Petrov Aleksandr Andreevich Nazarov Alena Mikhailovna Koldina Anton Vladimirovich Syroeshkin

Hyaluronidase and its modified analogs are clinically significant enzyme-based pharmaceuticals used to treat fibrosis, increase tissue permeability, and improve drug diffusion. While pharmacopeial quality control methods are well defined, scientific literature provides limited information about the physicochemical evaluation of such enzyme pharmaceuticals, necessitating a more holistic analytical approach. Commercial pharmaceuticals of hyaluronidase and its modified analog were analyzed using a combination of dynamic light scattering, infrared spectroscopy, and detection of intrinsic radiothermal emission (RTE). Dimensional characteristics were studied using a Zetasizer Nano ZSP (ZetasizerNano ZSP, Malvern Instruments, Malvern, UK) confirmed theoretical diameters of 5–8 nm, consistent with experimental values (6–8 nm). Fourier-Transform infrared spectroscopy (FTIR) (Agilent Cary 630, Agilent Technologies, Santa Clara, CA, USA) revealed characteristic transmission bands for the modified enzyme at 1464, 1448, 1326, 1158, and 1010 cm−1, confirming structural modification. RTE measurements using a TES-92 detector (TES Electrical Electronic Corp., Taipei, Taiwan) demonstrated a correlation between emission intensity and shelf life: 12.8 ± 0.8 µW/m2 for proper shelf-life samples, 8.3 ± 0.8 µW/m2 for six-month-expired, and 5.1 ± 1.0 µW/m2 for one-year-expired pharmaceuticals. The study offers a promising supplementary tool for pharmaceutical quality control of hyaluronidase-based drugs.

Scientia Pharmaceutica doi: 10.3390/scipharm94010001

Authors: Deepak Kulkarni Sanjay Pekamwar

Rosuvastatin calcium is a promising lipid-lowering agent and the drug of choice in hyperlipidemia. Conventional solid oral delivery of rosuvastatin is limited by its poor solubility and ultimately poor bioavailability. An attempt was made to fabricate the cocrystals of RSC for enhancing solubility and bioavailability. Cocrystals were prepared by a microwave synthesiser-assisted solvent evaporation technique with multiple cocrystal formers. Rosuvastatin-Ascorbic acid (RSC-AA) cocrystals showed the highest solubility (~5-fold increased) amongst all twenty drug-coformer combination (DCC). RSC-AA cocrystals (1:1 ratio) were further characterized by various analytical techniques like FTIR, DSC and XRD to confirm the formation of cocrystals. RSC-AA cocrystals also showed improved flow properties and compressibility in comparison with pure drug, and it was demonstrated using the SeDeM diagram. RSC-AA cocrystals were further formulated into an immediate-release tablet by implementing experimental optimization. Comparative dissolution study of the cocrystal and pure drug tablet revealed improved dissolution after cocrystallization. RSC-AA cocrystal tablet showed the % drug release of 95.61 ± 3.94 while RSC pure drug showed the drug release of 67.83 ± 3.29. In vivo pharmacokinetic analysis showed significant improvement in systemic availability and cumulative absorption of the drug. The peak plasma concentration (Cmax) for RSC pure drug was 13.924 ± 0.477 μg/mL, while RSC-AA cocrystals showed a peak plasma concentration of 22.464 ± 0.484 μg/mL. Area Under Curve (AUC) of RSC-AA cocrystal was also significantly greater compared to the pure drug. In the stability study analysis, the shelf life was calculated from a graphical method and was found to be around 34.58 months for RSC-AA cocrystal tablets and 19.87 months for RSC pure drug tablets, which indicates improved stability with cocrystallization. Overall, the cocrystallization resulted in significant improvement in dissolution and solubility of RSC.

Scientia Pharmaceutica doi: 10.3390/scipharm93040062

Authors: Kar Lee Heesoo Kim Jong Song Olena Sydorchuk Wong Ka Fai Isabella Rosellini Hongseok Kim Kian Lau Michael Gold Kyuho Yi

Injectable biostimulatory agents such as poly-L-lactic acid (PLLA), polycaprolactone (PCL), and calcium hydroxyapatite (CaHA) have emerged as key tools in regenerative aesthetics due to their ability to stimulate adipogenesis and adipocyte metabolic activity, enhance collagen production, and improve dermal quality. This review aimed to provide an updated synthesis of the role of these agents in adipocyte stimulation, focusing on their mechanisms of action, clinical efficacy, and therapeutic applications. A comprehensive search of the MEDLINE, PubMed, and Ovid databases was conducted for studies published from 2018 onward, including in vitro and in vivo experiments, randomized controlled trials, and observational studies, which were evaluated according to the Oxford Centre for Evidence-Based Medicine hierarchy. The findings demonstrated that PCL promotes adipose-derived stem cell differentiation and extracellular matrix remodeling, while PLLA exhibits dual effects on collagen synthesis and adipocyte stimulation, with clinical trials such as the SPLASH study confirming significant improvements in dermal thickness and adipogenesis. CaHA provided immediate volumizing benefits with long-term tissue regeneration, and innovative approaches including combination therapies and novel injection protocols expanded clinical applications. Overall, PLLA, PCL, and CaHA represent effective and versatile biostimulatory agents that support natural and durable outcomes in aesthetic practice. Nevertheless, the absence of large-scale trials and standardized protocols highlights the need for further research to optimize safety, efficacy, and long-term treatment strategies.

Scientia Pharmaceutica doi: 10.3390/scipharm93040061

Authors: Nithin Vidiyala Pavani Sunkishala Preethi Mandati Prashanth Parupathi Dinesh Nyavanandi

Over the last decade, additive manufacturing (AM) has been widely investigated for developing on-demand, patient-centric, and personalized medications. Among various AM techniques, fused deposition modeling (FDM), semi-solid extrusion (SSE), inkjet printing, binder jet printing, stereolithography (SLA), and selective laser sintering (SLS) have been most widely studied for developing simple and complex pharmaceutical medications. Implementing the AM platform enables decentralized manufacturing of medications at the hospitals and clinical sites. The dose and release profiles of the dosage forms can be tailored based on patient needs, providing flexibility to the physician. In fact, streamlining the AM process into a continuous manufacturing process equipped with process analytical technology (PAT) tools will ensure the manufacturing and delivery of safe and efficacious medications to the patient population. Complex medications, such as polypills, which are complex and time-consuming to manufacture using traditional manufacturing techniques, can be printed quickly using the AM approach. The pediatric patient population can be attracted to medication by printing the dosage forms with a geometry of interest. The AM platform can be integrated with artificial intelligence (AI) and health records to accelerate drug development and tailor medications based on patient conditions. Despite the various advantages that the AM platform brings to the pharmaceutical field, a few limitations, such as scalability, material innovation, secondary processing, and regulatory evolution, need to be addressed. This review article compares the advantages and limitations of the existing AM techniques along with a note on the recent advancements and future perspectives.

Scientia Pharmaceutica doi: 10.3390/scipharm93040060

Authors: Zsuzsanna Takáts Attila Almási Judit Szalai-Szolcsányi Tünde Ambrus Nóra Papp

In this study, a terminological and grammatical survey of essential and fatty oils of plant origin was performed in the selected Austrian, Hungarian, Spanish, and Belgian pharmacopoeias from the 18th to 19th centuries. The Latin-language prescriptions were analysed for their content, sections, and indications, and then translated from Latin into English, and supplemented with the source plants. Oil types were categorised based on their preparation and origin. Most oils belong to essential oils in Ph. Austriaca I–IV, Ph. Belgica, and Ph. Hungarica I (20 in each). Cooked oils are described as having the highest number in Ph. Hispanica (21), while pressed oils are also included in a high ratio in Ph. Hisp. (18) and Ph. Austriaca V (15). At the same time, those from minerals are described only in Ph. Belg. (2) and Ph. Hisp. (5). Latin terms are used in preparation methods, including the most concise descriptions in Ph. Austriaca V and Ph. Hg. I. This comprehensive study provides new linguistic data on the oils of herbs in the selected pharmacopoeias. Studies of essential oils have recently been progressing, and this analysis might help in understanding information from old pharmacopoeias.

Scientia Pharmaceutica doi: 10.3390/scipharm93040059

Authors: Miroslav Radenković

Biopharmaceuticals are medical drugs produced by means of biotechnology. In contrast with small-molecule (traditional) drugs, which are usually synthesized chemically, biopharmaceuticals are derived from biological sources, including tissues, cells, or microorganisms. Biopharmaceuticals comprise a wide extent of therapies, such as vaccines, monoclonal antibodies, cell therapies, recombinant proteins, and gene therapies, as well as biosimilars. These products are designed to become important treatment options for different diseases, including cancer, autoimmune pathological disorders, andinfectious diseases. The development of biopharmaceuticals often includes multifaceted processes, involving genetic engineering and cellular culture techniques, to guarantee efficacy and safety. Accordingly, biopharmaceuticals’ legislation is a key component for ensuring the highest quality of medical products, as well as protecting public health. As a rapidly developing area inside the pharmaceutical industry, biopharmaceuticals represent a significant advancing stage in modern medicine, offering targeted therapies that can improve patient outcomes. Accordingly, this paper seeks to provide current state-of-the-art didactic information, including better insight into various challenges related to biopharmaceuticals’ development, classification, medical use, legislation and ethics.

Scientia Pharmaceutica doi: 10.3390/scipharm93040058

Authors: Divya Wali Shivakumar H. Nanjappa Avichal Kumar Rushikesh Shinde

Docetaxel (DTX)-loaded polymeric nanoparticles composed of Eudragit RL and RS 100 were developed by solvent evaporation using D-α-tocopheryl polyethene glycol 1000 succinate as an emulsifier and optimised by Central Composite Design. The effects of homogenisation and sonication times on entrapment efficiency (%EE) and drug release (%DR) were statistically analysed across nine batches. Particle size (PS) ranged from 302 ± 1.0 to 502 ± 2.0 nm, and zeta potential (ZP) from 25.8 ± 2.5 to 42.9 ± 1.7 mV. %EE and %DR (pH 1.2 for 2 h, then pH 7.4 for 22 h, 40 mL medium at 37 ± 0.5 °C) ranged from 69.32 ± 3.77 to 92.71 ± 0.16% and 19.24 ± 3.03 to 49.17 ± 1.98%, respectively. Optimised DTX nanoparticles (DNPs) showed EE of 78.18 ± 0.56%, DR of 46.21 ± 1.41% at 24 h, PS of 357.9 ± 2.4 nm, and ZP of 42.9 ± 3.7 mV. Scanning electron microscopy revealed ~300 nm cuboidal particles with smooth surfaces. X-Ray Diffraction and Differential Scanning Colorimetry confirmed reduced drug crystallinity in DNPs. In vitro haemolysis assays showed ~11.5-fold lower haemolytic potential (p < 0.0001) versus DTX, confirming improved safety. Fluorescence microscopy indicated enhanced cellular uptake of DNPs in MDA-MB-231 cells, while cytotoxicity assays of DNPs showed a lower IC50 (39.52 µM) compared to DTX (60.81 µM), demonstrating superior anticancer efficacy. Overall, DNPs represent a promising oral chemotherapy platform for breast cancer management.

Scientia Pharmaceutica doi: 10.3390/scipharm93040057

Authors: Enrique Jiménez-Ferrer Tania Abarca-Salgado Azamar Vargas-Radilla José de Jesús Flores-Melgar Rodolfo Abarca-Vargas

Benign prostatic hyperplasia (BPH) and prostatitis are multifactorial urological disorders associated with chronic inflammation, oxidative stress, and androgenic imbalance. Dysphania ambrosioides (L.) Mosyakin & Clemants contains flavonoids and phenolic acids with well-recognised antioxidant and anti-inflammatory properties; however, its potential activity against the molecular targets of these prostatic disorders has not been systematically evaluated. A comparative quantitative analysis was performed using studies published between 2005 and 2025 that reported antioxidant activity (DPPH assay, IC50 in µg/mL) of D. ambrosioides extracts. Metabolites from extracts with IC50 values below the global mean (398.410 ± 81.810 µg/mL; n = 35) were selected for in silico prioritisation using OSIRIS, PASS, and ProTox 3.0, followed by molecular docking (CB-Dock2) against AR, 5AR2, COX-2, NLRP3, and α1A receptors. Luteolin and rosmarinic acid showed favourable binding energies (−9.5 to −7.7 kcal/mol) comparable in magnitude to reference drugs (finasteride −13.4, celecoxib −11.4, tamsulosin −7.3 kcal/mol). These metabolites, exhibited affinity for androgenic, inflammatory, and adrenergic targets, suggesting their potential to modulate key mechanisms underlying both BPH and prostatitis. This study integrates, for the first time, a quantitative assessment of antioxidant activity with a multitarget in silico analysis of D. ambrosioides, prioritising luteolin and rosmarinic acid as natural candidates with potential antioxidant, anti-inflammatory, and antiandrogenic properties relevant to prostatic health.

Scientia Pharmaceutica doi: 10.3390/scipharm93040056

Authors: Mio Ogawa Charles W. Crawford Ayumu Ishigaki Iri Sato-Baran David D. Ordinario Tadayoshi Miyashita

Bioactive ingredients are compounds, typically derived from natural sources, that provide specific health benefits or perform certain beneficial functions. Although they can play a role in maintaining good health, their effects can vary widely based on a person’s specific genotype and phenotype, leading to situations where certain ingredients induce beneficial responses for some individuals but not others. Herein, we report a method for the rapid discovery of relationships between genes, bioactive ingredients, and physiological effects. First, RNA-Seq was performed after applying 6 plant-derived ingredients to a three-dimensional skin model. After determining expression changes for each ingredient, these changes were ranked and visualized using score-based prediction models. Based on our analysis, we were able to quickly determine and visualize the effect (or lack thereof) of the ingredients on gene expression. Our findings demonstrate the utility of combining RNA-Seq with score-based models and visualizations for screening bioactive ingredients by gene expression, visualizing their impact based on ingredient or physiological effect, and the applicability of this method to any bioactive ingredient for rapid determination of potential ingredients relevant to maintaining health and wellness.

Scientia Pharmaceutica doi: 10.3390/scipharm93040055

Authors: Rigoberto Cabanillas-Ponce de León Feliznando Isidro Cardenas-Torres Noe Ontiveros Laura Aracely Contreras-Angulo Cristina Alicia Elisande-Romero Nayely Leyva-López Manuel de Jesús Bernal-Millán Jose Basilio Heredia Erick Paul Gutiérrez-Grijalva

Diabetes mellitus (DM) is a disease that affects over 537 million people worldwide and results in 6.7 million deaths annually. Conventional treatment of this disease focuses on lifestyle changes and drug administration. However, very few people can adhere to a healthier lifestyle, and drugs are difficult to access, especially in low- and middle-income countries. An alternative as an adjuvant to the treatment of DM is the phenolic compounds from plants with reported anti-diabetic effects. However, the bioavailability of these compounds is very low since they are affected by the gastrointestinal tract and xenobiotic metabolism. To improve the availability of these compounds, an emerging technology such as encapsulation is being used since it has been reported that the encapsulation of phenolic compounds improves both their bioaccessibility and bioavailability, as well as their bioactivity. In this review, we will focus on compiling the most up-to-date information on the different encapsulation processes of phenolic compounds and the antidiabetic effect of encapsulated phenolic compounds using the databases PubMed, Scopus, Web of Science, and Google Scholar. We will discuss the mechanisms, pathways, and receptors involved in the modulation of DM, especially those related to inflammation, oxidative stress, and insulin resistance.

Scientia Pharmaceutica doi: 10.3390/scipharm93040054

Authors: Pimvaree Aissara Ausanai Prapan Chanyatip Suwannasing

Radiotherapy (RT) is a standard treatment for cervical cancer, but its efficacy is often limited by tumor hypoxia and low radiosensitivity. Radiosensitizers that enhance RT without dose escalation are therefore of clinical interest. Alpha-mangostin (AM), a xanthone from Garcinia mangostana, exhibits anticancer and ROS-inducing properties. This study evaluated whether AM enhances radiosensitivity in vitro. Cytotoxicity (0–35 µM) was assessed by the MTT assay, and radiation sensitivity (0–6 Gy) was assessed by clonogenic survival. γ-H2AX immunofluorescence, cell cycle distribution, apoptosis induction, and clonogenic survival assessments were used to investigate the radiosensitization effect. AM showed dose-dependent cytotoxicity in HeLa cells at an inhibitory concentration 20 (IC20) of 13.67 µM while sparing fibroblasts. The radiation lethal dose 20 (LD20) was 1.4 Gy. However, combination treatment used AM at 12 µM (IC14) combined with 2 Gy (LD30) irradiation to avoid 50% cell death. AM enhanced G2/M arrest by 21.10% (p < 0.01) versus controls. In combination treatment, AM significantly increased γ-H2AX-positive cells to 48.2% (p < 0.0001), elevated apoptosis to 39.48% (p < 0.0001), and decreased clonogenic survival to 28% (p < 0.0001) compared with control. A combination index of about 0.9 indicated synergism. Therefore, AM effectively radiosensitized HeLa cells via increased DNA double-strand breaks and G2/M arrest.

Scientia Pharmaceutica doi: 10.3390/scipharm93040053

Authors: Ángel Daniel Campos-Juárez Octavio Rodríguez-Cortes Andrés Ademar Garcia-Nuñez Mónica Adriana Rodríguez-Cadena Jonathan B. Cortés-Serrano Carlos Zepactonal Gómez-Castro Itzel Pamela Torres-Avila Damaris Priscila Romero-Rodríguez Gamaliel Benítez-Arvizu Dean J. Naisbitt Mario Adán Moreno-Eutimio José Luis Castrejón-Flores

The γδ T cells belong to a subgroup of T cells known as non-conventional T cells due to their limited T cell receptor (TCR) repertoire and ability to recognize non-peptide antigens. They play a crucial role in combating infections and tumors. Vγ9Vδ2 T cells are typically activated by molecules containing diphosphate groups, collectively known as phosphoantigens (pAgs), through a non-canonical mechanism which involves the intracellular domain of butyrofilin (BTN)3A1 protein. However, no FDA-approved drugs have yet been shown to activate them, and the underlying cellular mechanisms remain unknown. In this study, we combined high-throughput virtual screening of an FDA-approved drug database with in vitro cellular assays to identify potential γδ T cells activators. Our findings demonstrate that Nitazoxanide (NTZ) and Tinidazole induce moderate elicited a statistically significant increase in interferon (IFN)-γ production of Vγ9Vδ2 T cells by their probably interaction with the pAg binding site of BTN3A1. Additionally, NTZ induces expression of CD107a, but only at the highest concentrations tested and promotes the upregulation of HLA-DR in total PBMCs and CD14+ monocytes. Blocking BTN3A with a specific antibody led to a marked reduction in all NTZ-induced activations. This work identifies NTZ as a previously unrecognized activator of γδ T cells, highlighting its immunomodulatory potential beyond its known clinical uses. These findings broaden our understanding of γδ T cells pharmacology and suggest new opportunities for drug repurposing and the design of novel chemical scaffolds. Further mechanistic studies will be essential to fully define how NTZ engages the BTN3A–γδ T cells axis.

Scientia Pharmaceutica doi: 10.3390/scipharm93040052

Authors: Mikołaj Grabarczyk Aleksandra Szychowska Sebastian Kozłowski Kasper Sipowicz Tadeusz Pietras Marcin Kosmalski Monika Różycka-Kosmalska

As a metabolism-controlling peptide, insulin affects activity of almost all tissues in human organisms, including the ones located in the central nervous system. By modifying glucose uptake and processing, as well as inducing anabolic effects, insulin alters functions of various nerve centers. Data from numerous clinical trials prove that such actions can have positive influence on cognitive processes or might be utilized as measures to control appetite, mood, and blood flow, or to prevent unfavorable mental states associated with diminished ability to maintain homeostasis. The intranasal route of administration provides an efficient and targeted delivery method, allowing insulin to be applied directly to different brain regions via the nasal mucosa. Such an approach can also reduce the risk of potential adverse effects associated with this medication, including drops in plasma glucose levels. This review gathers clinical studies’ findings on intranasal insulin’s neuromodulatory properties and its efficacy as additional treatment measure in several neuropsychiatric disease entities.

Scientia Pharmaceutica doi: 10.3390/scipharm93040051

Authors: Aganze Gloire-Aimé Mushebenge David Ditaba Mphuthi

Monkeypox (Mpox) has re-emerged as a global public health threat, with recent outbreaks linked to novel mutations that enhance viral transmissibility and immune evasion. The Mpox virus (MPXV), a double-stranded deoxyribonucleic acid (DNA) orthopoxvirus, shares high structural and enzymatic similarity with the variola virus, underscoring the need for urgent therapeutic interventions. While conventional antiviral development is time-intensive and costly, drug repurposing offers a rapid and cost-effective strategy by leveraging the established safety and pharmacological profiles of existing medications. This is a narrative integrative review synthesizing published evidence on drug repurposing strategies against MPXV. To address these issues, this review explores MPXV molecular targets critical for genome replication, transcription, and viral assembly, highlighting how the Food and Drug Administration (FDA)-approved antivirals (cidofovir, tecovirimat), antibiotics (minocycline, nitroxoline), antimalarials (atovaquone, mefloquine), immunomodulators (infliximab, adalimumab), and chemotherapeutics (doxorubicin) have demonstrated inhibitory activity against the virus using computational or experimental approaches. This review further evaluates advances in computational methodologies that have accelerated the identification of host-directed and viral-directed therapeutic candidates. Nonetheless, translational challenges persist, including pharmacokinetic limitations, toxicity concerns, and the limited efficacy of current antivirals such as tecovirimat in severe Mpox cases. Future research should integrate computational predictions with high-throughput screening, organ-on-chip technologies, and clinical pipelines, while using real-time genomic surveillance to track viral evolution. These strategies establish a scalable and sustainable framework for the MPXV drug discovery.

Scientia Pharmaceutica doi: 10.3390/scipharm93040050

Authors: Patrycja Huber Aniela Zubek-Biełuś Paweł Lipiński Anna Żuk

Pharmaceutical care in European countries is at various stages of development. Although the problem of occupational burnout affects many professions, it is particularly relevant among healthcare workers, such as pharmacists. Studies assessing pharmacists’ life satisfaction and factors influencing the level of occupational burnout play an important role in social pharmacy. Therefore, the present study aimed to evaluate the impact of providing pharmaceutical care on the professional life satisfaction of pharmacists in Poland. This study was conducted as an anonymous online survey. It included pharmacists who are members of the professional self-government in Poland. A custom-designed questionnaire was used for data collection, and 91 completed questionnaires were obtained. The respondents were divided into four groups according to their professional experience: up to 5 years, 6–10 years, 11–20 years, and over 20 years. In response to questions regarding job satisfaction and the willingness to provide pharmaceutical care, the respondents gave affirmative answers. Pharmacists in Poland have a positive perception of the impact of pharmaceutical care on the prestige of their profession. Currently, the pharmaceutical care services most commonly provided are those financed by the State; however, pharmacists are willing to engage in such activities and expect an expansion of the scope of reimbursed services. Consequently, pharmacists express dissatisfaction with the current stage of pharmaceutical care implementation in Poland. Those who provide pharmaceutical care feel more appreciated in their profession, do not experience psychological strain, do not feel uncomfortable when communicating with patients, and are not afraid of the responsibility associated with providing such services. Nevertheless, they consider it an additional workload in their professional duties.

Scientia Pharmaceutica doi: 10.3390/scipharm93040049

Authors: Andrea Vásquez Sofía Echeverri-Gaviria Marcela Manrique-Moreno

Changes in membrane lipid composition constitute a key bacterial resistance mechanism. In Staphylococcus aureus, phosphatidylglycerol undergoes lysine modification to form lysyl-phosphatidylglycerol, a cationic lipid that reduces the net negative surface charge and thereby enhances resistance to cationic antimicrobial peptides. In this study, we examined the influence of lysyl-PG on the membrane activity of three antimicrobial peptides with distinct physicochemical characteristics: LL-37, F5W Magainin II, and NA-CATH:ATRA-1-ATRA-1. Model membranes composed of phosphatidylglycerol and cardiolipin were supplemented with increasing molar fractions of lysyl-phosphatidylglycerol, and peptide–membrane interactions were characterized using Fourier-transform infrared spectroscopy. Membrane fluidity was evaluated through shifts in the symmetric methylene stretching bands, while changes in interfacial polarity were assessed via the carbonyl and phosphate asymmetric stretching bands. LL-37 induced pronounced disruption of anionic bilayers, an effect progressively attenuated by lysyl-phosphatidylglycerol, particularly within the hydrophobic core. F5W Magainin perturbed both hydrophobic and interfacial regions across a broader range of lysyl-phosphatidylglycerol concentrations, whereas NA-CATH:ATRA-1-ATRA-1 primarily targeted interfacial domains, with minimal disruption of acyl chain order. Increasing lysyl-PG content modulated the extent of bilayer disorder and dehydration at the hydrophobic–hydrophilic interface, with each peptide exhibiting a distinct interaction profile. Collectively, these findings provide mechanistic insights into lysyl-PG-mediated modulation of peptide activity and highlight the role of lipid remodeling as a bacterial defense strategy.

Scientia Pharmaceutica doi: 10.3390/scipharm93040048

Authors: Adina-Elena Grasu Roman Senn Christiane Halbsguth Alexander Schenk Veronika Butterweck Giulia Zecchin Ionel I. Mangalagiu Cătălina-Ionica Ciobanu Anca Miron

Hydroethanolic Cucurbita pepo seed extracts are traditionally used for alleviating lower urinary tract symptoms (LUTS), yet their mechanisms remain unclear. Adenosine, a purine nucleoside involved in neuromodulation and smooth muscle relaxation, was recently identified in C. pepo seeds. Since A1 adenosine receptors (A1AR) suppress parasympathetic bladder overactivity by inhibiting acetylcholine (ACh) release, we investigated to which extent purines from pumpkin seed extracts contribute to A1AR activation. Complementary antioxidant capacity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Three hydrophilic seed extracts containing different adenosine levels (0.60–1.18 mg/g dw) were evaluated for agonist activity using a cAMP inhibition assay. The most active extract showed an EC50 of 40.22 µg/mL. Selective removal of adenosine shifted the dose–response curve rightward, while further elimination of an adenosine derivative increased the EC50 to 212.10 µg/mL, confirming adenosine as the principal active compound. Guanosine and inosine did not exhibit A1AR agonist or allosteric effects. All samples exhibited measurable but weak antioxidant activity (IC50 = 1.02–4.19 mg/mL), consistent with their low total phenolic content. These findings underscore the importance of accounting for naturally occurring agonists in plant extracts to avoid overestimating receptor-mediated effects in vitro which are not translatable in vivo.

Scientia Pharmaceutica doi: 10.3390/scipharm93040047

Authors: Jozef Zima Eva Nováková Miroslava Špaglová Miroslava Šupolíková

This review explores the pharmacological potential of chondroitin sulfate and fucoidan as immunomodulatory agents targeting N-acetylgalactosaminidase (nagalase) to normalize immune responses. Nagalase, an enzyme produced by tumor and virus-infected cells, contributes to immune suppression by deactivating macrophage-activating factor. Both chondroitin sulfate and fucoidan, as representatives of glycosaminoglycans and heteropolysaccharides, exhibit significant potential in inhibiting nagalase activity, thereby restoring immune functionality. Chondroitin sulfate, a key component of the extracellular matrix, demonstrates anti-inflammatory and tissue-regenerative properties by modulating nuclear factor (NF)-κB pathways and cytokine expression. Fucoidan, a sulfated polysaccharide derived from brown seaweed, enhances immune responses through macrophage and natural killer cell activation, while also exhibiting antiviral and anticancer activities. This dual action positions these compounds as promising agents for therapeutic interventions in chronic inflammatory conditions, cancer, and infectious diseases. The synergistic effects of chondroitin sulfate and fucoidan highlight their potential to address the root causes of immune dysregulation. This review aims to elucidate the underlying mechanisms of action and explore the clinical applications of these compounds within the framework of innovative immunotherapeutic strategies. However, current evidence is limited by the predominance of preclinical studies and variability in experimental models. Well-designed clinical trials are needed to validate their efficacy for therapeutic use.

Scientia Pharmaceutica doi: 10.3390/scipharm93030046

Authors: Kashish Azeem Babita Aneja Amad Uddin Asghar Ali Haider Thaer Abdulhameed Almuqdadi Shailja Singh Rajan Patel Mohammad Abid

We aimed to investigate the interaction mechanism of transport protein Human serum albumin (HSA) with a synthesized compound, QP-11, with tested antimalarial properties to monitor the changes in the protein because of QP-11 binding. The interaction between the antimalarial compound QP-11 and HSA was thoroughly investigated through a multidimensional approach, utilizing UV-VIS spectroscopy, fluorescence, time-resolved fluorescence, and CD (Circular dichroism), alongside molecular docking techniques. Our findings unveiled a robust 1:1 binding pattern, signifying a strong affinity between QP-11 and HSA. Employing static quenching, evidenced by time-resolved fluorescence spectroscopy, QP-11 was observed to induce fluorescence quenching of HSA, particularly binding to subdomain IIA. Thermodynamic parameters indicated that van der Waals forces and hydrogen bonding predominantly facilitated the binding, with increased temperature compromising complex stability. The 3D fluorescence and CD results demonstrated QP-11-induced conformational changes in HSA. Both experimental and in silico analyses suggested a spontaneous, exothermic binding reaction. The profound impact of the QP-11–HSA interaction underscores the potential for QP-11 in antimalarial drug development, encouraging further exploration for dose design and enhanced pharmacodynamic and pharmacokinetic properties.

Scientia Pharmaceutica doi: 10.3390/scipharm93030045

Authors: Evgenia Panou Nikolaos Tsafantakis Gokhan Zengin Konstantia Graikou Christos Ganos Nikolas Fokialakis Ioanna Chinou

This study aimed to characterize the chemical composition and evaluate the biological activities of the aerial parts of Alkanna corcyrensis Hayek (AC), an endemic Greek species not previously studied. Phytochemical analysis of the methanolic extract was performed using UHPLC-ESI-Q-TOF–MS/MS combined with molecular networking analysis. Additionally, the total phenolic content (TPC) and total flavonoid content (TFC) were determined. Chromatographic separations were carried out to isolate major compounds, and the antioxidant capacity, along with enzyme inhibitory activity, was assessed. The analysis led to the tentative identification of 86 compounds, including 67 phenolic compounds (mainly caffeic acid derivatives and flavonoid glycosides), 10 pyrrolizidine alkaloids of trachelanthamidine, platynecine, and retronecine types, and nine organic and fatty acid derivatives. Among these, one flavonol glycoside (kaempferol-O-malonyl methyl ester hexoside) and three pyrrolizidine alkaloids (9-sarracinoyl-trachelanthamidine/isoretronecanol, retronecine-pentoside, and trachelanthamidine/isoretronecanol-hexoside) were reported for the first time. The extract exhibited high TPC (74.45 mg GAE/g extract) and TFC (46.66 mg GAE/g extract). Chromatographic separations resulted in the isolation of five major metabolites, namely rosmarinic acid, danshensu, kaempferol-3-O-glucoside, kaempferol-3-O-galactoside, and quercetin-3-O-glycoside. Biological evaluation revealed considerable antioxidant activity and inhibitory effects against α-glucosidase (6.65 mmol ACAE/g extract). Overall, this study highlights the remarkable phytochemical diversity and richness of AC among alkanet species and demonstrates its promising antioxidant potential, laying the foundation for further investigations towards its future exploitation.

Scientia Pharmaceutica doi: 10.3390/scipharm93030044

Authors: Mikhail E. Blokhin Sergey A. Borisov Mariia A. Gromova Yulia V. Meshkova Nataliya A. Zhukova Sophia V. Nikonova Igor P. Zhurakovsky Olga A. Luzina Mikhail V. Khvostov Dmitry A. Kudlay Nariman F. Salakhutdinov

Metabolic syndrome is characterized by a group of metabolic disorders that can lead to the development of cardiovascular diseases, obesity and type 2 diabetes mellitus (T2DM). Nowadays, there are several groups of drugs for the treatment of T2DM, but there is no one that would not have significant side effects and suitable for most patients. In our previous study, it was shown that the (S)-2-ethoxy-3-phenylpropanoic acid derivative containing isopimaric acid moiety exhibited pronounced antidiabetic activity. In the present study, a series of (S)-2-ethoxy-3-phenylpropanoic acid derivatives containing an isopimaric acid moiety with various aromatic substituents at position 16 were synthesized. The synthesized compounds were tested for their ability to improve glycemic control and to counter lipid abnormalities in C57BL/6Ay mice placed on a high-fat/high-cholesterol diet. Of all tested compounds, the 2-NO2-phenyl derivative (16d) had the most pronounced effect in decreasing blood glucose and serum triglyceride levels. All the compounds displayed a relatively safe profile in the animal studies carried out in this work. Therefore, it can be concluded that chemical modification of isopimaric acid may enhance its efficacy as an antidiabetic agent as part of the potential glitazar.

Scientia Pharmaceutica doi: 10.3390/scipharm93030043

Authors: Acharaporn Duangjai Kwanruthai Tadpetch Vatcharin Rukachaisirikul Chutima S. Vaddhanaphuti Maleeruk Utsintong

Obesity is a major global health concern associated with increased risks of chronic diseases and mortality. Inhibiting pancreatic lipase, a key enzyme in dietary fat absorption, presents a promising therapeutic approach. This study aimed to evaluate the inhibitory potential of piperidine derivatives (1 and 2) and pyrrolidine derivatives (3–13) against pancreatic lipase (PL) through both enzymatic assays and molecular docking simulations. Among the tested compounds, compound 12 demonstrated the highest PL inhibitory activity with IC50 0.143 ± 0.001 mg/mL and the strongest binding energy (−8.24 kcal/mol), attributed to extensive hydrogen bonding with Gly76, Phe77, Asp79, and His151. Compounds 10 and 13 also exhibited notable inhibitory activity, attributed to their extensive hydrogen bond network with residues Gly76, Phe77, Asp79, and His151. Particularly the presence and position of hydroxy and carbonyl groups and the length of alkyl side chains critically influenced binding stability and specificity. These findings demonstrate that specific structural modifications in pyrrolidine derivatives significantly affect pancreatic lipase inhibition. Compound 12, with its optimal molecular architecture and interaction profile, stands out as the most promising candidate for further development as an anti-obesity agent, with compounds 10 and 13 offering additional scaffolds for future optimization.

Scientia Pharmaceutica doi: 10.3390/scipharm93030042

Authors: Alessandro Colletti Valentina Citi Alma Martelli Marzia Pellizzato Enzo Riccardi Giancarlo Cravotto

Berberine, a natural isoquinoline alkaloid, has been shown to improve glycemic control, lipid metabolism, and blood pressure regulation. However, its poor bioavailability has limited widespread clinical use. ToBeRock® is a self-emulsifying formulation designed to enhance the bioaccessibility of berberine. This retrospective, real-world pilot study conducted through community pharmacies with pharmaceutical care services aimed to evaluate the metabolic and hemodynamic effects of ToBeRock® in adults with impaired fasting glucose (IFG). Sixty adults with IFG (FPG 100–125 mg/dL) were enrolled through territorial pharmacies offering pharmaceutical services. Patients were retrospectively grouped into two cohorts: a Low-Dose Group (ToBeRock® 1 capsule/day) and a High-Dose Group (ToBeRock® 2 capsules/day). Capillary blood sampling and in-pharmacy blood pressure measurements were recorded at baseline (T0), 4 weeks (T1), and 8 weeks (T2). Evaluated parameters included fasting glucose, HbA1c, lipid profile (total cholesterol, LDL, HDL, triglycerides), systolic and diastolic blood pressure (SBP/DBP), and oxidative stress markers (FORT, FORD). Both cohorts showed statistically significant reductions in fasting glucose (p < 0.001), LDL (p = 0.036 Low-Dose/p = 0.039 High-Dose), and triglycerides (p = 0.012/0.009) after 8 weeks of treatment. The High-Dose Group experienced a greater improvement in HbA1c (−0.26%, p = 0.041) and a mild but statistically significant increase in HDL (p = 0.049). Improvements in oxidative balance were observed with significant reductions in FORT (p = 0.019/0.011), increases in FORD (p = 0.033/0.008), and a favorable shift in the REDOX index (p = 0.012/0.006). Systolic blood pressure decreased by −6.3 mmHg in the Low-Dose Group (p = 0.031) and −7.6 mmHg in the High-Dose Group (p = 0.048), while diastolic pressure dropped by −3.9 mmHg (p = 0.044) and −4.2 mmHg (p = 0.051), respectively. This real-world, retrospective analysis highlights the potential clinical benefit of ToBeRock® in improving glycemic, lipid, oxidative, and hemodynamic profiles. The High-Dose Group demonstrated more consistent and significant results, supporting the dose-responsive efficacy of the bioavailable formulation and the value of pharmacy-based monitoring of nutraceutical interventions.

Scientia Pharmaceutica doi: 10.3390/scipharm93030041

Authors: José Jailson Lima Bezerra

Some species of Cyperaceae are used in the treatment of gastrointestinal disorders by traditional communities in several countries, including Kenya, Nepal, Pakistan, and India. Although these ethnomedicinal uses are being confirmed through in vivo pharmacological trials, many plants in this family still lack scientific investigation. In this context, the present study aimed to review the pharmacological potential of Cyperaceae species in experimental models of gastrointestinal disorders and correlate it with the phenolic compounds and flavonoids present in these plants. The articles were retrieved from different databases, from the first report on the topic published in 1997 to August 2025. A total of 10 Cyperaceae species were identified that showed pharmacological potential against gastrointestinal disorders, including representatives of the genera Cyperus (6 spp.), Fimbristylis (2 spp.), Lagenocarpus (1 spp.), and Pycreus (1 spp.). The extracts of these plants demonstrated potential antiulcerogenic, gastroprotective, antidiarrheal, and intestinal anti-inflammatory effects in rodent models of ulcerative colitis, with particular attention on Cyperus rotundus L. A diverse array of bioactive compounds were identified in the Cyperaceae family, including luteolin, kaempferol, caffeic acid, quercetin, ferulic acid, rutin, myricetin, gallic acid, chlorogenic acid, apigenin, catechin, and orientin. These phytochemicals have been widely studied in experimental models of gastrointestinal disorders. It is likely that the flavonoids and phenolic compounds identified in Cyperaceae species are related to the pharmacological potential of these plants and can be used in the treatment of gastrointestinal disorders. Additional studies are needed to investigate the pharmacological potential of other Cyperaceae used empirically in traditional medicine for the treatment of diseases affecting the digestive system.

Scientia Pharmaceutica doi: 10.3390/scipharm93030040

Authors: Luis P. López-López Nora A. Hernández-Cuevas Karla Y. Acosta-Viana Víctor E. Arana-Argáez Julio C. Torres-Romero Glendy M. Polanco-Hernández

Trypanosoma cruzi is the protozoan parasite that causes Chagas disease, affecting approximately 6–7 million people worldwide. The current treatment lacks efficacy in the chronic phase of the disease. This study aims to determine the in vitro synergistic activity of concomitant therapy (benznidazole with β-caryophyllene oxide) against Trypanosoma cruzi, assess its cytotoxicity, and propose the mechanism of this synergism through in silico analysis. The tested concentrations of the treatment demonstrated hemocompatibility (<5% hemolysis) and no cytotoxicity (>80% cell viability). Additionally, synergistic activity against the parasite was confirmed, reducing epimastigote viability by up to 80%. In this work, in silico analysis revealed that β-caryophyllene oxide also binds to the T. cruzi ABC channel in regions localized to amino acids 108–271 and 399–558, suggesting this interaction could inhibit it. This treatment emerges as a promising candidate for Chagas disease therapy. It lacks cytotoxic and hemolytic activity while exhibiting synergism against the parasite, such as through the inhibition of ABC channels, as suggested in silico.

Scientia Pharmaceutica doi: 10.3390/scipharm93030039

Authors: Ender Volkan Chad Schou Jandirk Sendker Panagiotis Karanis

Antibiotic resistance is on the rise, rendering discovery of new antibacterial sources essential. Biofilms drive resistance and cause complications in healthcare settings, emphasizing that preventing pathogenic biofilms is vital. Quercus species, with medicinal potential, might provide novel approaches against pathogens. Cyprus hosts four understudied Quercus species—Q. alnifolia Poech, Q. × campitica Hadjik. & Hand, Q.coccifera var. calliprinos (Webb) Boiss., and Q. infectoria subsp. veneris (A.Kern.) Meikle—where Q. alnifolia and Q. × campitica are endemic. This study assessed the antibacterial, antibiofilm, and preformed biofilm reduction effects of their ethanolic leaf extracts on Staphylococcus aureus (ATCC 6538) and performed phytochemical analysis. Because biofilm formation often drives recalcitrance, sub-minimum inhibitory concentrations (sub-MIC) of Quercus extracts were tested on planktonic and biofilm S. aureus. At a sub-MIC of 0.156 mg/mL, Q. alnifolia and Q. × campitica extracts displayed notable antibiofilm activity. Liquid chromatography–mass spectrometry of Q. alnifolia revealed several bioactive compounds where these compounds may support wider antibacterial effects. This is the first report of Q. alnifolia and Q. × campitica ethanolic leaf extracts with antibiofilm activity against S. aureus and associated phytochemical analyses. These results support further practical research into the potential applications of these Quercus extracts as antibacterial materials.

Scientia Pharmaceutica doi: 10.3390/scipharm93030038

Authors: Marianna Maretina Anna Egorova Arina Il’ina Nadezhda Krylova Maxim Donnikov Oleg Glotov Anton Kiselev

Spinal muscular atrophy (SMA) is a severe neurodegenerative disorder that has an approved treatment that can still be improved. Antisense oligonucleotides (AONs) are currently delivered intrathecally for SMA therapy based on SMN2 gene splicing correction, and high concentrations are required to achieve an improvement of the disease symptoms. In this study, AONs were introduced into SMA fibroblast cell cultures by means of an arginine–histidine-rich peptide carrier that had been decorated with iRGD ligands. Due to the protected and receptor-mediated nature of AON delivery within these complexes, low concentrations can be used. We assessed the RNA-binding characteristics, cytotoxicity, size, and zeta potential of AON/carrier complexes as well as the efficiency of SMN2 gene splicing correction following transfections. After testing a variety of AON/carrier formulations, we selected those that produced the best outcomes. The AON/carrier complexes that were found to be the most effective significantly increased the proportion of full-length SMN transcripts and the quantity of nuclear gems. Thus, we demonstrated the potential of delivering therapeutic AONs into SMA cells using a ligand-modified peptide carrier.

Scientia Pharmaceutica doi: 10.3390/scipharm93030037

Authors: Karem Fouda Rasha S. Mohamed

Hyperlipidemia, oxidative stress, and excessive inflammatory cytokine production are risk factors for depression. The potential preventive effects of essential oils (EOs) such as cumin and fennel EOs on depression may stem from their hypolipidemic, antioxidant, and anti-inflammatory activities. This work aimed to investigate the effects of cumin and fennel EO nanocapsules in a mouse model of depression caused by a high-fat diet (HFD) and chronic mild stress (CMS) using both in silico and in vivo studies. The cumin and fennel EOs were extracted, analyzed by GC-MS, and encapsulated in nano-form using gum Arabic and maltodextrin as wall materials. The freeze-dried nanocapsules were evaluated in HFD/CMS-treated mice. Molecular docking was used to examine the significance of the oils’ compounds in blocking the active sites of hydroxymethylglutaryl-CoA (HMG-CoA) and indoleamine 2,3-dioxygenase (IDO). According to the molecular docking results, the interactions between EO components and HMG-CoA or IDO indicate that these EOs may have hypercholesterolemic and antidepressive effects. Cumin and fennel EO nanocapsules showed hypolipidemic, antioxidant, and anti-inflammatory effects in vivo. This was demonstrated by the down-regulation of oxidants (ROS, MDA, and NO) and inflammatory markers (TLR4, TNF-α, and IL-6) in the brain, changes in lipid profile parameters, and the up-regulation of antioxidant enzymes (SOD, CAT, and GSH). The in silico and in vivo outputs revealed the potential preventive impact of cumin and fennel EO nanocapsules against depression-like states in the mouse model through the prevention of dyslipidemia, neuroxidation, and neuroinflammation. More human studies are needed to fully understand the antidepressive effects of cumin and fennel EO nanocapsules.

Scientia Pharmaceutica doi: 10.3390/scipharm93030036

Authors: Carlos Antonio Sánchez-Valdeolivar Alan Carrasco-Carballo Jorge Organista-Nava Jesús Sandoval-Ramírez Berenice Illades-Aguiar

Cervical cancer affects 661,000 women worldwide; as a result, new treatment alternatives are still being sought, with steroid oximes being the most prominent. However, the molecular targets where steroid oximes exert their anticancer activity remain unknown. In this study, reports of the activity in cell lines were obtained, and the targets associated with cervical cancer were identified using bioinformatics tools, based on two- and three-dimensional structural similarity analysis. Subsequently, molecular targets were analyzed via molecular docking using Schrödinger software v.2022-4 to determine their effects compared with reference drugs. Interrelated proteins and isolated proteins were observed, suggesting both the multi-target and single-target activity of steroid oximes. The analysis revealed that 60% of the 42 identified proteins had previously been reported in the literature and were associated with cervical cancer in processes related to cell proliferation, invasion, migration, and apoptosis. Among them, SRC, IGF1R, and MDM2 showed feasibility for multi-target interaction, which is consistent with the lower IC50 values reported for oximes in cervical cancer cell lines (HeLa and CaSki). This finding suggests that steroid oximes are multi-target molecules that can inhibit the proteins associated with cervical cancer, particularly through the IGF1R, MDM2, and SRC pathways related to cell proliferation and apoptosis, serving as a guideline for the future design of new steroidal oximes.

Scientia Pharmaceutica doi: 10.3390/scipharm93030035

Authors: Ana Sofia Martins Cristina Monteiro Ana Paula Duarte

Oral anticoagulants, including warfarin, a vitamin K antagonist, have been used for anticoagulation therapy, but their limitations, such as drug interactions and complex dosing, have prompted the development of direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, dabigatran, and edoxaban. This study reviews the interactions of both warfarin and DOACs, particularly those influenced by cytochrome P450 enzymes and P-glycoprotein. Warfarin is metabolized by various cytochrome P450 isoforms, making it vulnerable to interactions with medications and herbs that modulate these enzymes. In contrast, DOACs, while having fewer interactions, are still affected by strong inducers or inhibitors of cytochrome 3A4 and P-glycoprotein, depending on the specific drug. Some herbs may also interfere with these pathways. Continuous monitoring of these interactions is crucial to ensure the safe use of oral anticoagulants. The findings underscore the importance of identifying and understanding these interactions to improve patient safety and guide appropriate anticoagulant therapy.

Scientia Pharmaceutica doi: 10.3390/scipharm93030034

Authors: Diana Ana-Maria Nițescu Horia Păunescu Mihnea Costescu Bogdan Nițescu Laurențiu Coman Ion Fulga Oana Andreia Coman

Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment of actinic keratoses (AK), pre-malignant entities that have the risk of transformation into skin carcinomas. The hypothesis that diclofenac increases granular layer development in the mice tail model, having an anti-psoriatic effect, was demonstrated in a previous study in which 1% and 2% diclofenac ointment was evaluated. The aim of the present study was to perform experimental research on the topical effect of diclofenac in the mice tail model, by testing 4% and 8% diclofenac ointment, which is presented in the first part of the manuscript. In the second part of the manuscript, we also aimed to conduct a literature review regarding topical diclofenac uses in specific dermatological entities by evaluating the articles published in PubMed and Scopus databases during 2014–2025. The studies regarding the efficacy of topical diclofenac in dermatological diseases such as AK and field cancerization, actinic cheilitis, basal cell carcinoma, Bowen disease, Darier disease, seborrheic keratoses, and porokeratosis, were analyzed. The results of the experimental work showed a significant effect of 4% and 8% diclofenac ointment on orthokeratosis degree when compared to the negative control groups. Diclofenac in the concentration of 4% and 8% significantly increased the orthokeratosis degree compared to the negative control with untreated mice (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test) and to the negative control with vehicle (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test). The mean epidermal thickness was increased for the diclofenac groups, but not significantly when compared to the control groups. The results are concordant with our previous experiment, emphasizing the need for future clinical trials on the use of topical diclofenac in psoriasis.

Scientia Pharmaceutica doi: 10.3390/scipharm93030033

Authors: Cheng-Yuan Lin Zi-Han Gao Chi-Wai Cheung Edmund Cheung So Sheng-Nan Wu

Cumulative inhibition of voltage-gated Na+ channel current (INa) caused by high-frequency depolarization plays a critical role in regulating electrical activity in excitable cells. As discussed in this review paper, exposure to certain small-molecule modulators can perturb INa during high-frequency stimulation, influencing the extent of cumulative inhibition and electrical excitability in excitable cells. Carbamazepine differentially suppressed transient or peak (INa(T)) and late (INa(L)) components of INa. Moreover, the cumulative inhibition of INa(T) during pulse-train stimulation at 40 Hz was enhanced by lacosamide. GV-58 was noted to exert stimulatory effect on INa(T) and INa(L). This stimulated INa was not countered by ω-conotoxin MVIID but was effectively reversed by ranolazine. GV-58′s exposure can slow down INa inactivation elicited during pulse-train stimulation. Lacosamide directly inhibited INa magnitude as well as promoted this cumulative inhibition of INa during pulse-train stimuli. Mirogabalin depressed INa magnitude as well as modulated frequency dependence of the current. Phenobarbital can directly modulate both the magnitude and frequency dependence of ionic currents, including INa. Previous investigations have shown that exposure to small-molecule modulators can perturb INa under conditions of high-frequency stimulation. This ionic mechanism plays a crucial role in modulating membrane excitability, hereby supporting the validity of these findings.

Scientia Pharmaceutica doi: 10.3390/scipharm93030032

Authors: Marina Parchaykina Milena Simakova Tatyana Kuzmenko Anastasia Zavarykina Elvira Revina Elizaveta Sadovnikova Igor Grunyushkin Svetlana Kiryukhina Victor Revin

This study investigated the changes in protein composition and DNA content in damaged somatic nerves when exposed to insulin-like growth factor-1 (IGF-1). Using electrophoretic protein separation in polyacrylamide gel (PAG) and spectrophotometry, the transection was shown to be accompanied by a significant decrease in the quantitative content of total protein, certain protein fractions and DNA, both in the proximal and distal segments of the nerve conductor. Against the background of the intramuscular administration of IGF-1, intensive DNA synthesis and the protein composition stabilization of somatic nerves at the earlier post-traumatic stages were observed. By means of Raman scattering (RS-spectroscopy) and recording action potentials (APs), the enhanced recovery of the physicochemical condition of the nerve fiber membrane and its functional activity, indicating regeneration activation in the somatic nerves after damage, was revealed. IGF-1 was most likely to stimulate cytoskeleton protein synthesis through launching the mitogen-activated protein kinase signal pathway (MAPK/ERK), resulting in the increased expression of the genes related to the remyelination and functioning recovery of damaged nerve conductors.

Scientia Pharmaceutica doi: 10.3390/scipharm93030031

Authors: Mykhailo Dronik Maryna Stasevych

This study systematically reviews the non-traditional pharmacological effects of diclofenac, a well-known nonsteroidal anti-inflammatory drug, to explore its potential for drug repositioning beyond its established analgesic and anti-inflammatory applications. A comprehensive literature search was conducted using the PubMed, Scopus and Web of Science databases, covering studies from 1981 to 2025. It was revealed that over 94% of records in Scopus and Web of Science are duplicated in PubMed, so the latter was used for the search in our study. After duplicate removal and independent screening, 89 from 1123 retrieved studies were selected for the search. The analysis revealed a broad spectrum of diclofenac’s non-traditional pharmacological activities, including neuroprotective, antiamyloid, anticancer, antiviral, immunomodulatory, antibacterial, antifungal, anticonvulsant, radioprotective, and antioxidant properties, primarily identified through preclinical In vitro and In vivo studies. These effects are mediated through diverse molecular pathways beyond cyclooxygenase inhibition, such as modulation of neurotransmitter release, apoptosis, and cellular proliferation. Diclofenac showed potential for repositioning in oncology, neurodegenerative disorders, infectious diseases, and immune-mediated conditions. Its hepatotoxicity and cardiovascular risks necessitate strategies like advanced drug formulations, dose optimization, and personalized medicine to enhance safety. Large-scale randomized clinical trials are essential to validate these findings and ensure safe therapeutic expansion.

Scientia Pharmaceutica doi: 10.3390/scipharm93030030

Authors: Nithin Vidiyala Pavani Sunkishala Prashanth Parupathi Preethi Mandati Srujan Kumar Mantena Raghu Rami Reddy Kasu Dinesh Nyavanandi

The objective of the current research is to investigate the role of Neusilin US2 as a porous carrier for improving the drug loading and stability of Ezetimibe (EZB) by hot melt extrusion (HME). The amorphous solid dispersions (ASDs) were developed from 10–40% of drug loading using Kollidon VA 64 (Copovidone) as a polymer matrix and Neusilin US2 as a porous carrier. The solid-state characterization of EZB was studied using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). The formulation blends were characterized for flow properties, and CTC (compressibility, tabletability, compactibility) profile. The in-vitro drug release profiles were studied in 0.1 N HCl (pH 1.2). The incorporation of Neusilin US2 has facilitated the development of ASDs up to 40% of drug loading. The CTC profile has demonstrated excellent tabletability for the ternary (EZB, copovidone and Neusilin) dispersions over binary dispersion (EZB and copovidone) formulations. The tablet formulations with binary (20%) and ternary (30% and 40%) dispersions have demonstrated complete dissolution of the drug in 30 min in 0.1 N HCl (pH 1.2). The incorporation of copovidone has prevented the recrystallization of the drug in the solution state. Upon storage of formulations at accelerated conditions, the stability of ternary dispersion tablets was preserved attributing to the entrapment of the drug within Neusilin pores thereby inhibiting molecular mobility. Based on the observations, the current research concludes that it is feasible to incorporate Neusilin US2 to improve the drug loading and stability of ASD systems.

Scientia Pharmaceutica doi: 10.3390/scipharm93030029

Authors: Stefano Notarangelo Renato Lombardi Massimo Lombardi Giovanna Liguori Marco Taurchini Marco Sperandeo Leonardo Specchiulli Paola Conte Fabrizia Checola Emilia Langella Antonio Giordano Roberto Bava Stefano Ruga

Small-cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis despite initial responsiveness to chemotherapy. Platinum-based chemotherapy with etoposide has long been the standard first-line treatment, but recent advances in immunotherapy have improved outcomes. Phase III trials, including IMpower133 and CASPIAN, demonstrated that adding immune checkpoint inhibitors, such as atezolizumab and durvalumab, to chemotherapy significantly enhances overall survival (OS) and progression-free survival (PFS). This case report describes a 76-year-old former smoker diagnosed with extensive-stage SCLC (ES-SCLC) following the detection of a left lower lung mass. The patient underwent combination therapy with carboplatin, etoposide, and atezolizumab, followed by maintenance atezolizumab. The patient demonstrated a sustained response to treatment, with significant tumor regression and no evidence of disease progression. Despite advanced age and comorbidities, treatment was well-tolerated, with no severe adverse events. Serial imaging over 24 months confirmed sustained disease stability, with regression of mediastinal lymphadenopathy and no new lesions. This case highlights the potential for prolonged disease control in select SCLC patients treated with chemo-immunotherapy. The absence of significant toxicities underscores the feasibility of immunotherapy even in elderly patients with comorbidities. These findings support the role of atezolizumab as a key component of ES-SCLC treatment and suggest the need for further research on predictors of durable response.

Scientia Pharmaceutica doi: 10.3390/scipharm93030028

Authors: Juan Luis Peréz-Salas Martha Rocío Moreno-Jiménez Luis Medina-Torres Nuria Elizabeth Rocha-Guzmán María Josefa Bernad-Bernad Rubén Francisco González-Laredo José Alberto Gallegos-Infante

The topical application of curcumin can act directly on the tissue, but there are problems related to solubility and permeation. Bigels combine hydrogels and organogels to enhance the release and transport of bioactives through the skin. The aim of this study was to develop bigels for the topical delivery of curcumin. Employing a rheology test, it was found that all bigels showed a solid-like behavior structure (G′ > G″) with stiffness increasing with higher organogel content. The principle of time–temperature superposition (TTS) was used to generate master curves. Microscopy revealed a morphological structure that depended on the organogel/hydrogel ratio. The bigels exhibited a pH compatible with that of human skin, and the curcumin content met the standards for uniform dosage. Thermal characterization showed the presence of three peaks in coconut oil bigels and two peaks in castor oil bigels. Bigels with a 45% castor oil organogel/55% hydrogel ratio exhibited a longer controlled release of curcumin, while bigels with coconut oil showed a faster release. The release data were fitted to mathematical models indicating non-Fickian release. The permeability of curcumin through Strat-M membranes was investigated, and greater permeation was observed with increasing organogel content. The developed bigels could be a promising option for the topical delivery of curcumin.

Scientia Pharmaceutica doi: 10.3390/scipharm93020027

Authors: Nathareen Chaiwangrach Sirikan Mukda Prapapan Temkitthawon Nitra Nuengchamnong Sarita Pinmanee Thapakorn Somboon Panatpong Boonnoun Kornkanok Ingkaninan

Hemp essential oils are rich in bioactive compounds, including terpenes and cannabinoids, yet standardized analytical methods for their simultaneous quality control are limited. This study aimed to (i) validate a static headspace gas chromatography–mass spectrometry (SHS-GC-MS) method for simultaneous quantification of 20 terpenes and 2 cannabinoids and (ii) apply it to fingerprint essential oils from four hemp strains, including local (HRDI2, HRDI5) and internationally cultivated (Charlotte’s Angel, Cherry Wine) varieties. The method met AOAC validation criteria, with detection limits of 0.025–0.5 µg/mL for terpenes and 1 µg/mL for cannabinoids. Quantitation limits ranged from 0.1–1 µg/mL for terpenes and 5 µg/mL for cannabinoids. Intraday precision (%RSD) ranged from 0.27–11.00%, while interday precision ranged from 3.14–13.89%. The method recoveries ranged from 85.12–115.47%. Precision and recovery confirmed the method’s reliability. Multivariate statistical analysis identified 82 metabolites, revealing distinct chemical fingerprints among strains, and emerged as newly identified chemotype markers, supporting chemotype classification. This work demonstrates, for the first time, a solvent-free, automatable SHS-GC-MS approach for simultaneous terpene and cannabinoid profiling in hemp essential oils, enabling both qualitative and quantitative characterization and supporting regulatory compliance for the development of standardized phytopharmaceutical products.

Scientia Pharmaceutica doi: 10.3390/scipharm93020026

Authors: Héctor Iván Saldívar-Cerón Jorge Arturo Vargas-Camacho Sonia León-Cabrera Paola Briseño-Díaz Ari Evelyn Castañeda-Ramírez Axel Eduardo Muciño-Galicia María Regina Díaz-Domínguez

Small-molecule glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent an innovative advancement in oral therapeutics, addressing key limitations associated with injectable peptide-based incretin therapies. These nonpeptidic agents exert their actions primarily through non-canonical binding orthosteric sites within the GLP-1 receptor transmembrane domain, enabling selective G protein (Gs)-biased signaling with reduced β-arrestin-mediated adverse effects. Orforglipron has notably advanced through Phase 3 clinical development, demonstrating significant reductions in hemoglobin A1c and body weight (up to 7.9%) with favorable tolerability. Conversely, promising candidates such as danuglipron and lotiglipron were discontinued due to hepatotoxicity, underscoring critical safety concerns intrinsic to small-molecule GLP-1RA development. Current clinical candidates, including GSBR-1290, CT-996, and ECC5004, continue to offer substantial potential due to their oral bioavailability, simplified dosing regimens, and favorable gastrointestinal tolerability. Nevertheless, challenges persist regarding hepatic safety, pharmacodynamic variability, and limited long-term outcome data. This review integrates current structural, pharmacological, and clinical evidence, highlights key mechanistic innovations—including biased agonism, covalent binding strategies, and allosteric modulation—and discusses future directions for this rapidly evolving therapeutic class in metabolic disease management.

Scientia Pharmaceutica doi: 10.3390/scipharm93020025

Authors: Marcos Morales-Reyna Elisa Elvira Figueroa-Angulo José Espinoza-Hicks Alejandro Camacho-Dávila César López-Camarillo Laura Isabel Vázquez-Carrillo Alfonso Salgado-Aguayo Ángeles Carlos-Reyes Violeta Deyanira Álvarez-Jiménez Jonathan Puente-Rivera María Elizbeth Alvarez-Sánchez

Prenylated chalcones have garnered attention as potential anticancer agents due to their ability to modulate multiple cancer-related pathways. In this study, we synthesized and evaluated nine novel prenylated chalcone derivatives for their antiproliferative effects against castration-resistant prostate cancer (CRPC) cell lines, DU145 and PC3. Among these, compounds 6d and 7j demonstrated potent cytotoxic activity, with IC50 values comparable to cisplatin, and exhibited selective toxicity towards cancer cells over non-tumorigenic RWPE-1 cells. Mechanistic investigations revealed that these compounds induce apoptosis via mitochondrial membrane depolarization and increased late apoptotic events. Flow cytometry confirmed activation of both early and late apoptotic pathways. These findings highlight the potential of chalcone derivatives 6d and 7j as promising therapeutic candidates for CRPC treatment and support further development of chalcone-based molecules in precision oncology.

Scientia Pharmaceutica doi: 10.3390/scipharm93020024

Authors: Raymar Andreina Lara Garcia Jesús Alberto Afonso Urich Andreina Isabel Afonso Urich Dalibor Jeremic Johannes Khinast

Improving the manufacturability of drug formulations via direct compression has been of great interest for the pharmaceutical industry. Selecting excipients plays a vital role in obtaining a high-quality product without the wet granulation processing step. In particular, for diluents which are usually present in a larger amount in a formulation, choosing the correct one is of utmost importance in the production of tablets via any method. In this work, we assessed the possibility of manufacturing a small-molecule drug product, omeprazole, which has been historically manufactured via a multi-step processes such as wet granulation and multiple-unit pellet system (MUPS). For this purpose, four prototypes were developed using several diluents: a co-processed excipient (Microcelac®), two granulated forms of alpha-lactose monohydrate (Tablettose® 70 and Tabletose® 100), and a preparation of microcrystalline cellulose (Avicel® PH102) and lactose (DuraLac® H), both of which are common excipients without any enhancement. The tablets were produced using a single punch tablet press and thoroughly characterized physically and chemically in order to assess their functionality and adherence to drug product specifications. The direct compression process was used for the manufacturing of all proposed formulations, and the prototype formulated using Microcelac® showed the best results and performance during the compression process. In addition, it remained stable over twelve months under 25 °C/60% RH conditions.

Scientia Pharmaceutica doi: 10.3390/scipharm93020023

Authors: Paula Hosana Fernandes da Silva Jemima Isnardo Fernandes Matheus Pontes de Menezes Fabrícia Lima Fontes-Dantas André Luiz Nunes Freitas Rayane Efraim Correa Ulisses Cesar de Araujo Dayane Teixeira Ognibene Cristiane Aguiar da Costa Cláudio Carneiro Filgueiras Alex Christian Manhães Júlio Beltrame Daleprane Angela de Castro Resende Graziele Freitas de Bem

Polychlorinated biphenyls (PCBs) are synthetic chemical compounds that have bioaccumulated and contaminated the entire global ecosystem, causing neurotoxic effects. However, polyphenols may have protective effects against this neurotoxicity. We aimed to investigate the neuroprotective effect of a hydroalcoholic extract of fresh leaves of Alpinia zerumbet (ALE), which is rich in polyphenols, on the neurobehavioral changes induced by 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126). We divided C57BL/6 male mice into four groups (n = 40): Control, Control + ALE, PCB, and PCB + ALE. We administered the ALE (50 mg/kg/day) through drinking water and PCB 126 (2 mg/kg/once a week) intraperitoneally for four weeks. The mice were subjected to the elevated plus maze (EPM) and open field (OF) tests in the last week of treatment. PCB 126 reduced locomotor activity, DOPAC levels, dopamine turnover, and D2 receptor expression. This compound also increased lipid peroxidation, tyrosine levels, and BAX expression in the cerebral cortex. Notably, ALE treatment prevented locomotor activity reduction and increased DOPAC levels, dopamine turnover, and D2 receptor expression. Moreover, the extract prevented the PCB-induced increases in BAX expression and lipid peroxidation. Finally, the ALE increased SOD antioxidant activity. Our investigation highlights that using the ALE may serve as a therapeutic strategy against PCB-induced neurotoxicity.

Scientia Pharmaceutica doi: 10.3390/scipharm93020022

Authors: Ivone Vanessa Mañozca-Dosman Alberto Aragón-Muriel Dorian Polo-Cerón

Benzimidazoles are considered a promising class of bioactive heterocyclic compounds that show a wide variety of useful biological properties due to their structural similarities to nucleotides such as purines. Among these properties, great attention has been given to the antibacterial activity exhibited by molecules containing a benzimidazole nucleus in their structure since recent research results have shown the potential of such molecules as alternatives in the fight against bacterial resistance. When these compounds have phenylsubstituted groups in the 2-position of the imidazole ring, a series of molecules can be obtained with generally improved pharmacological activity. These types of compounds are suitable for the formation of stable complexes with several transition metals, including nickel and copper; such compounds have also exhibited many biological properties in different reports. Accordingly, this brief review focuses on recent work on the synthesis and characterization of metal complexes of Ni(II) and Cu(II) with ligands derived from 2-(phenylsubstituted) benzimidazole that were subsequently evaluated for antibacterial activity.

Scientia Pharmaceutica doi: 10.3390/scipharm93020021

Authors: Ivelina Tsacheva Dzhamal Uzun

Background: The aim of this study was to investigate the radioprotective efficacy of polymer complexes constructed from amifostine (WR-2721) and poly(hydroxyoxyethylene phosphate)s with different molecular weights. The use of suitable polymers for the immobilization of radioprotective drugs is aimed at improving or obtaining important new properties. Methods: The radioprotective efficacy of the compounds was investigated by cytotoxicity and the survival of mouse embryonic fibroblasts MEF LIG4+/+ and MEF LIG4−/− cells irradiated with 2, 6 and 12 Gy in the presence of amifostine (WR-2721) and its polymer complexes. Results: The radioprotective efficacy of the polymer complexes constructed of amifostine (WR-2721) and poly(hydroxyoxyethylene phosphate)s with different molecular weights showed promising activity and dose regimens. Conclusions: Cytotoxicity studies for tested cell lines MEF LIG4+/+ and MEF LIG4−/− cells showed that the polymer complexes were not toxic when equivalent doses of the drug amifostine (WR-2721) were applied to the cells. Irradiated MEF LIG4+/+ cells demonstrated an increase in the surviving fraction when pre-treated with 0.5–5 mM polymer complexes when equivalent doses of amifostine (WR-2721) were applied to the cells and irradiated. The radioprotective efficacy had increased when the cells MEF LIG4+/+ were irradiated with 12 Gy. These findings demonstrate that poly(hydroxyoxyethylene phosphate)s are suitable carriers of the radioprotective drug amifostine (WR-2721). They further suggest that they may be interesting for researchers seeking new challenges in discovering advanced radioprotective active substances.

Scientia Pharmaceutica doi: 10.3390/scipharm93020020

Authors: Ioana Lavinia Radulian Georgiana Nitulescu Anca Zanfirescu George Mihai Nitulescu

The adverse effects of protein kinase inhibitors (PKIs) and other anticancer therapies were compared using FDA Adverse Events Reporting System (FAERS) data. The dataset included 159 FDA-approved anticancer drugs (71 PKIs, 88 nonPKIs) and analyzed 8216 unique adverse event (AE) terms. PKIs showed fewer systemic toxicities, with an average of 230.1 distinct AEs per drug, compared to 537.7 in nonPKIs. Hematologic AEs were significantly lower in PKIs (e.g., febrile neutropenia: 1.93% vs. 5.25%; thrombocytopenia: 2.18% vs. 3.87%), coupled with a lower incidence of infections (6.87% vs. 14.2%) and immunosuppressive effects. However, gastrointestinal and skin-related AEs were more common in PKIs (e.g., diarrhea: 13.95% vs. 8.36%). A higher proportion AEs in the PKI group (14.57%) were classified under “Investigations”, compared to the nonPKI group (9.87%). The frequency of “Skin and subcutaneous tissue disorders” AEs was twice as high in the PKI group. Clustering analysis grouped drugs by AE profiles, showing that PKIs formed more homogeneous clusters, while nonPKIs had broader variability. Multi-kinase inhibitors with VEGFR activity were linked to dermatologic AEs, likely due to EGFR inhibition in basal keratinocytes. Despite PKIs’ targeted mechanisms, resistance remains a challenge, requiring biomarker-driven strategies. This study highlights PKIs’ improved tolerability but emphasizes using personalized treatment approaches to optimize efficacy and safety.

Scientia Pharmaceutica doi: 10.3390/scipharm93020019

Authors: Vivien Bárdos Rita Szolláth Petra Tőzsér Arash Mirzahosseini Bálint Sinkó Réka Angi Krisztina Takács-Novák

Most novel active pharmaceutical ingredients have low water solubility; therefore, solubility-enhancing methods are applied. The aim of the present investigation is to study the impact of nine commonly used pharmaceutical excipients (fillers, surfactants, cyclodextrins, polymers) on solubility, permeability and their relationship. This is crucial for ensuring optimal bioavailability. Carbamazepine, naproxen and pimobendan were chosen as model compounds due to their different acid–base properties. Equilibrium solubility was measured by the traditional shake flask method. Effective permeability was determined by the PAMPA model. Measurements of ionizable compounds were carried out at three pH values. The pH-dependent change in the investigated parameters is maintained even in the presence of excipients. Fillers resulted in a slight or no effect, while the impact of other excipients showed a significant concentration dependence. The impact of excipients was influenced by the structure and ionization state of the molecules. The dominance of the ionized form moderates the impact of excipients. The changes in solubility were more pronounced than in the case of permeability. By examining the effect of the ionization state and interactions with excipients, this work supports the development of formulations that enhance solubility with minimal impacts on permeability. Additionally, it can serve as good basis for preformulation studies and design optimization.

Scientia Pharmaceutica doi: 10.3390/scipharm93020018

Authors: Aaryan Dwivedi Jobanjit S. Phulka Peyman Namdarimoghaddam Zachary Laksman

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, often involving a strong genetic background. Polygenic risk scores (PRSs) combine the cumulative effects of multiple genetic variants to quantify an individual’s susceptibility to CVD. Pharmacogenomics (PGx) can further personalize treatment by tailoring medication choices to an individual’s genetic profile. Even with these potential benefits, the extent to which PRS can be integrated into the PGx of CVD remains unclear. Our review provides an overview of current evidence on the application of PRS in the PGx of CVD, examining clinical utility and limitations and providing directions for future research. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews protocol, we conducted a comprehensive literature search in PubMed, EMBASE, and the Web of Science. Studies investigating the relationship between PRS in predicting the efficacy, adverse effects, or cost-effectiveness of cardiovascular medications were selected. Of the 1894 articles identified, 32 met the inclusion criteria. These studies predominantly examined lipid-lowering therapies, antihypertensives, and antiplatelets, although other medication classes (e.g., rate-control drugs, ibuprofen/acetaminophen, diuretics, and antiarrhythmics) were also included. Our findings showed that PRS is most robustly validated in lipid-lowering therapies, especially statins, where studies reported that individuals with higher PRSs derived the greatest reduction in lipids while on statins. Studies analyzing antihypertensives, antiplatelets, and antiarrhythmic medications demonstrated more variable outcomes, though certain PRSs did identify subgroups with significantly improved response rates or a higher risk of adverse events. Though PRS was a strong tool in many cases, we found some key limitations in its applicability in research, such as the under-representation of non-European-ancestry cohorts in the examined studies and a lack of standardized outcome reporting. In conclusion, though PRS offers promise in improving the efficacy of PGx of CVD by enhancing the personalization of medication on an individual level, several obstacles, such as the need for including a broader ancestral diversity and more robust cost-effectiveness data remain. Future research must (i) prioritize validating PRS in ethnically diverse populations, (ii) refine PRS derivation methods to tailor them for drug response phenotypes, and (iii) establish clear and attainable guidelines for standardizing the reporting of outcomes.

Scientia Pharmaceutica doi: 10.3390/scipharm93020017

Authors: Lucia Dubiel-Hoppanova Alzbeta Filipova Stanislava Bukatova Katarina Ondacova Matus Tomko Bohumila Jurkovicova-Tarabova Michal Dubovicky Eliyahu Dremencov Lubica Lacinova

Maternal depression negatively affects the neurodevelopment of offspring, but its pharmacological treatment during gestation remains controversial. This study reports the consequences of maternal depression and/or prenatal antidepressant treatment with mirtazapine on offspring early neurodevelopment via an animal model of maternal depression induced by pregestational chronic unpredictable stress (CUS). Offspring from four groups were studied: nonstressed vehicle-treated dams, nonstressed mirtazapine-treated dams, stressed vehicle-treated dams, and stressed mirtazapine-treated dams. The hippocampal excitability of offspring was examined in primary hippocampal cultures established on the first postnatal day, reflecting mostly prenatal development, and in hippocampal slices prepared on postnatal days 11–13, reflecting an early postnatal development. The pregestational CUS modeling of maternal depression moderately suppressed offspring hippocampal excitability in primary cultures but facilitated it in slices. Mirtazapine administered to CUS-exposed dams partly rectified the changes observed in primary cultures of pups from untreated dams and, more prominently, in slices. Mirtazapine itself negatively affected the hippocampal excitability of nonstressed dam offspring in primary culture, and this effect was diminished in slices. Since altered hippocampal neurotransmission might be responsible, at least in part, for the neuropsychopathologies frequently observed in the offspring of depressed mothers, and mirtazapine was able to partly relieve such changes, this treatment may be also beneficial during the prenatal and perinatal periods.

Scientia Pharmaceutica doi: 10.3390/scipharm93020016

Authors: Anarkul S. Kishkentayeva Mohammad Saleh Hamad Mikhail A. Pokrovsky Zhanar R. Shaimerdenova Aigerim S. Adekenova Gulnara K. Mambeterzina Victor A. Savelyev Andrey G. Pokrovsky Elvira E. Shults

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes, the development of compounds with higher anticancer efficacy and a lower level of side effects is an important task in modern pharmaceutical chemistry. Herein, a mild and convenient method for the preparation of N1-substituted 3-(1,2,3-triazolyl-methoxycarbonyl)coumarins or bis(coumarine-3-carboxylate)bis(triazole)alkandiyl by the copper(I)-catalyzed Huisgen cycloaddition reaction of readily available coumarin-3-carboxylic acid propynyl ester with azides or diazides has been presented. The synthesized compounds have been tested for their cytotoxicity on various cancer and noncancerous cell lines using the MTT assay. All new compounds were nontoxic on normal epithelial VERO cells. Two derivatives exhibited selectivity towards HPV-negative human cervical cancer cells, C33 A, with excellent activities in low concentrations (GI50 4.4–7.0 µM). In vitro mechanistic studies showed that bis(coumarine)bis(triazolylester) conjugate 3 induced time-dependent apoptosis in cervical cancer cell lines C33 A and CaSki, at the GI50 concentration, as measured by Annexin V-FITC/PI staining. The most active coumarin–triazolyl ester conjugate 2g possessed anticancer activities, as indicated by its ability to induce S/G2 phase cell cycle arrest at a low concentration and early apoptosis in CaSki cells. The obtained results revealed the potential of new compounds as anticancer agents, particularly against cervical cancer.

Scientia Pharmaceutica doi: 10.3390/scipharm93020015

Authors: Christiane Halbsguth Verena M. Merk Jürgen Drewe Georg Boonen Veronika Butterweck

The use of herbal medicines containing Petasites hybridus extracts has a long history in the treatment of various ailments. The observed effects are primarily due to pharmacologically active compounds such as petasin, isopetasin, and neopetasin. In evidence-based phytotherapy, extracts from leaves and rhizomes are applied for different indications. While leaf extracts are administered to treat allergic rhinitis symptoms, rhizome extracts are utilized among others in the management of gastrointestinal spasms and migraines. The quality and source of plants are critical for producing authorized herbal medicinal products. Although the preparation of P. hybridus leaf extracts from cultivated plant material is already established, the rhizomes used for preparing extracts are still derived from commercial wild collections. However, switching to cultivation is desirable to ensure consistent quality and availability. For regulatory purposes, comparative pharmacological studies are needed to assess the bioactivity of plant material from different sources. Therefore, this study analyzed rhizome extracts from wild harvesting and cultivation for their petasin composition (i.e., isopetasin, neopetasin, petasin) and spasmolytic effects on Ca2+-dependent precontracted guinea pig ileum ex vivo. The results confirm petasins as active compounds of P. hybridus rhizome extracts. Moreover, they demonstrate that the total content of petasins determines the spasmolytic effects, regardless of the individual composition of the different petasins. No significant differences in efficacy were found between cultivated and wild-collected rhizomes, demonstrating that cultivated material is a reliable, consistent, and sustainable alternative for P. hybridus rhizome extract production.

Scientia Pharmaceutica doi: 10.3390/scipharm93010014

Authors: Marvin A. Soriano-Ursúa Marlet Martínez-Archundia Ahmet Kilic Teresa Pérez-Capistran Miriam A. Hernández-Zamora Juan E. López-Ramos Eunice D. Farfán-García

Boron-containing compounds (BCCs) have been proposed for the treatment of diabetes and its complications. Recent studies have reported an improvement in the design and development of pharmaceutical formulations (often gels) containing boric acid applied to the foot ulcers of humans diagnosed with diabetes. The proposed mechanisms of action of boric acid include antimicrobial effects, the modulation of inflammation and metabolism, and the induction of cell differentiation. On the other hand, recent studies have suggested that boronic acids are potent antibacterial and antifungal compounds, effective modulators of inflammation, and inducers of vascular regeneration as well as inducers of healing, and they confer attractive properties such as adhesion, interaction, and the formation of complexes in formulations. Moreover, only a handful of studies conducted in animals have suggested the effective role of some BCCs as potent enhancers of wound healing, including their actions on induced and/or infected wounds in animals with disrupted metabolism. Also, it should be mentioned that no strong interactions between boric acid and the boronic acids present in formulations have been described. The developed combination could act as an additive and complementary therapy in the treatment of diabetic ulcers in humans. Further studies are required to support the hypothesis that this combination acts through diverse mechanisms to improve healing while avoiding or limiting a local or disseminated infection. Furthermore, the safety of BCCs used for foot ulcers should be established, as should the role of these formulations as a complementary therapy in current protocols for treating patients with diabetic foot ulcers.

Scientia Pharmaceutica doi: 10.3390/scipharm93010013

Authors: Massimiliano Quici Elena Martini Davide Giustivi Maria Calloni Chiara Cogliati Alba Taino Antonella Foschi Andrea Gori Paolo Zappa Francesco Casella Arianna Bartoli Leyla La Cava Alessia Meschia Rosita Celano Francesco Urso Dario Cattaneo Antonio Gidaro

Most cardiological drugs need intravenous administration to have a fast effect in an emergency. Intravenous administration is linked to complications, such as tissue infiltration and thrombophlebitis. Aiming to supply an effective tool for the development of appropriate policies, this systematic review provides practical recommendations about the diluent, pH, osmolarity, dosage, vesicant properties, and phlebitis rate of the most commonly used cardiological drugs evaluated in randomized controlled trials (RCTs) till 31 August 2024. The authors searched for available IV cardiological drugs in RCTs in PUBMED EMBASE®, EBSCO-CINAHL®, and Cochrane Controlled Clinical trials. Drugs’ chemical features were obtained online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, an osmolarity > 600 mOsm/L, and a high incidence of phlebitis reported in the literature, as well as vesicant drugs, require utmost caution during administration. A total of 857 papers were evaluated and 316 studies were included. A total of 84 cardiological drugs were identified, of which only 31 (37%) can be safely infused via a peripheral route. Thrombolytics and anticoagulants are considered the safest classes of drugs, with only one drug flagged as a “red flag” medication. However, a higher percentage of drugs in other categories meet the “red flag” criteria, including antiarrhythmics (52%), antiplatelet agents (67%), diuretics (67%), antihypertensives (70%), other drugs (77%), and vasoconstrictors and inotropics (89%). Understanding the physicochemical properties of cardiological drugs is essential for significantly improving patient safety and preventing administration errors and local side effects.

Scientia Pharmaceutica doi: 10.3390/scipharm93010012

Authors: Juan Manuel Guzmán-Flores Fernando Martínez-Esquivias Antistio Alviz-Amador Guadalupe Thonanzyn Avilés-Rodríguez Michel Fabricio García-Azuela

Background: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, and current treatments have significant side effects. Cannabidiol (CBD), a compound derived from Cannabis sativa, has demonstrated promising anticancer properties. However, further investigation is required to elucidate its underlying molecular mechanisms. Methods: Network pharmacology and molecular docking analysis approaches were utilized. Molecular targets of CBD and CRC-associated genes were identified using the Swiss Target Prediction, Malacards, and DisGeNet databases. Protein–protein interactions were analyzed using the STRING and Cytoscape. Ontology enrichment was conducted using ShinyGO, and gene expression and immune infiltration were evaluated with UALCAN and TISIDB. Results: We found 95 common genes between CRC and CBD targets. Six major genes (ANXA5, IGF1R, JAK2, MAPK8, MDM2, and PARP1) were particularly interesting due to their high connectivity and role in relevant metabolic pathways. The results of the molecular docking analysis indicated that CBD interacts favorably with these genes, modulating critical pathways such as RAS/MAPK and PI3K-AKT/FoxO, which are involved in cell proliferation, apoptosis, and cell cycle regulation. ANXA5 and JAK2 were identified as particularly relevant, as they correlated significantly with immune cell infiltration, suggesting a role in the immunoregulation of the tumor microenvironment. Conclusions: CBD has the potential to modulate key molecular processes in CRC through specific pathways and core genes, presenting itself as a possible complementary therapy to improve efficacy and reduce the adverse effects of conventional treatments.

Scientia Pharmaceutica doi: 10.3390/scipharm93010011

Authors: Kengo Hori Yuki Kurauchi Shunsuke Kotani Hari Prasad Devkota

Matcha is reported to have high content of some bioactive components such as catechins, theanine, and caffeine, and its consumption is increasing worldwide. Several analytical methods have been established for matcha powder and bioactive compounds, but most of them are based on HPLC methods. This study focused on NMR as an analytical method for simple quantitative analysis of the functional components of matcha. The analytical conditions were established by preparing extract and solvent fractions, evaluating hygroscopicity, and examining quantitative NMR parameters. The analytical performance was evaluated, and the developed analytical condition was also applied to matcha powder by directly mixing in NMR solvent without pre-extraction. Caffeine, epicatechin, epicatechin-3-O-gallate, epigallocatechin-3-O-gallate, epigallocatechin, gallocatechin-3-O-gallate, and gallocatechin were quantified. Analysis of matcha and normal green tea powder suggested the possibility of distinguishing between matcha and green tea powder by the ratio of caffeine content and total catechins content. The qNMR method can be adopted for the simple analysis of the amount of caffeine and catechin compounds in the powders and extracts.

Scientia Pharmaceutica doi: 10.3390/scipharm93010010

Authors: Edwin Carlos Enciso-Roca Jorge Luis Arroyo-Acevedo Pablo Williams Común-Ventura Johnny Aldo Tinco-Jayo Enrique Javier Aguilar-Felices Mahomi Bertha Ramos-Meneses Rosa Elizabeth Carrera-Palao Oscar Herrera-Calderon

Chenopodium quinoa sprouts possess a superior nutritional profile relative to conventional quinoa seeds, which is mainly attributable to their germination process. Sprouting quinoa is able to preserve its substantial nutritional value while enhancing its bioavailability and digestibility. The aim of this study was to evaluate the gastroprotective effects of hydroalcoholic extracts of three varieties of quinoa sprouts (pasankalla, yellow maranganí, and black coito). The chemical compounds were determined using LC-MS (Liquid Chromatography–Mass Spectrometry). Antioxidant activity was determined using two analytical methods, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). To evaluate the gastroprotective effects of these hydroalcoholic extracts in Holtzman male rats, a gastric lesion was induced with 96% ethanol after the administration of the hydroalcoholic extract of the three varieties of C. quinoa sprouts. Our phytochemical analysis results reveal the presence of amino acids (valine, leucine, isoleucine, phenylalanine, tryptophane, proline, tyrosine, and arginine, among others) and their derivatives, organic acids, monosaccharides, lipids, nucleobases/nucleosides, steroids, triterpene saponins, and coumarins. The pasankalla, yellow maranganí, and black coito varieties exhibited antioxidant capacities of 36.70, 32.32, and 34.63 µmol Trolox equivalent (TE)/mg of extract for the DPPH radical and 56.61, 41.56, and 52.09 µmol TE/mg of extract for the ABTS radical, respectively. The percentage of antisecretory efficiency at a dose of 500 mg/kg for the pasankalla, yellow maranganí, and black coito varieties was 34.13%, 30.67%, and 26.67%, respectively, and the anti-ulcer effect, expressed as a percentage of inhibition of ulcer formation, was 74.7%, 67.4%, and 69.5%, respectively. In contrast, the groups treated with ranitidine and sucralfate exhibited percentages of 59.0% and 67.4%, respectively. The pasankalla quinoa exhibits more significant antioxidant activity and a stronger gastroprotective effect compared to the other varieties examined in this study. In conclusion, the hydroalcoholic extracts of the three varieties of C. quinoa sprouts exhibited a gastroprotective effect, and the pasankalla variety at a dose of 500 mg/kg exhibited a stronger protective effect on the gastric mucosa of the rats.

Scientia Pharmaceutica doi: 10.3390/scipharm93010009

Authors: José Jailson Lima Bezerra Anderson Angel Vieira Pinheiro Antônio Fernando Morais de Oliveira

Cancer is one of the leading causes of mortality worldwide, and the currently available therapies are often associated with severe side effects, including nephrotoxicity, hepatotoxicity, and cardiotoxicity. In this context, essential oils (EOs) have stood out as a less toxic natural alternative, with their anticancer potential widely investigated in in vitro and in vivo studies. The present study aimed to review, for the first time, the chemical composition, anticancer potential, and biological safety of EOs extracted from species of the Cyperaceae family. Research was conducted in different databases, covering publications from the first report on the topic in 1989 to November 2024. This review highlights 33 Cyperaceae species known to produce essential oils, with sesquiterpenes (67%) identified as the predominant compounds. The notable compounds across multiple species include cyperene, cyperotundone, caryophyllene oxide, and mustakone. Regarding the pharmacological potential, the EOs of Cyperus rotundus, Cyperus kyllingia, and Cyperus longus exhibited high cytotoxic activity against the HCT-116, HepG2, MCF-7, HeLa, and NCI-H187 cell lines. The mechanisms of action associated with the anticancer effect of EOs include DNA fragmentation, cell cycle arrest, and induction of apoptosis. Acute toxicity reports indicate that only the EOs of Cyperus articulatus have been evaluated in rodents and deemed biologically safe.

Scientia Pharmaceutica doi: 10.3390/scipharm93010008

Authors: Franc Capdevila Finestres Daida Alberto Armas Antoni Miró Manzano Verónica Hernández García Yeray Sosa Alonso Arturo Hardisson de la Torre Carmen Rubio Armendáriz

Introduction: Omeprazole is commonly prescribed for conditions associated with excess gastric acid, including gastroesophageal reflux and Helicobacter pylori infection. Spain ranks highest among Organization for Economic Co-operation and Development (OECD) countries in omeprazole consumption (measured in doses per 1000 inhabitants per day, DHD), indicating potential overuse and misuse. Community pharmacists are pivotal in collaborating with healthcare professionals to address safety risks and improve patient outcomes. Objective: This study aims to profile omeprazole users to inform pharmaceutical care (PC) strategies that address patient-specific needs and improve treatment safety. Methods: We conducted an observational, cross-sectional study (CEIm Code FCF-OME-2023-01) involving 100 omeprazole users at a community pharmacy in Barcelona from November 2023 to May 2024. Data were collected via clinical interviews using a Data Collection Questionnaire. Results: Among the omeprazole users, 49% were male, 51% female, and 56% were over the age of 65. A significant proportion (71%) exhibited long-term omeprazole use, and 30% were polymedicated (taking five or more medications). Notably, 52% of patients reported no history of gastric symptoms. Additionally, 22% reported using omeprazole occasionally, following short-term, on-demand treatment regimens, while 78% adhered to a chronic daily dosing schedule. Among these patients, 29.5% demonstrated poor treatment adherence. The analysis of medication-related problems (MRPs) among the 78 patients using omeprazole daily and chronically revealed that the most prevalent MRPs were “unnecessary medication”, “lack of adherence”, “wrong administration”, “drug interactions”, and “lack of knowledge regarding medication use”. Based on STOPP criteria, 45% of users were candidates for deprescribing or dose adjustment. Conclusions: The high incidence of MRPs among omeprazole users highlights the need for enhanced pharmaceutical care (PC). Proactive pharmacist interventions, including deprescribing, dose adjustments, and prescriber collaboration, can reduce adverse medication outcomes and promote safer omeprazole use.

Scientia Pharmaceutica doi: 10.3390/scipharm93010007

Authors: Ali El-Kasaby Christian Nanoff Stephane Nizet Cornelius Tschegg Michael Freissmuth

Ulcerous lesions can arise in primary skin cancers and upon infiltration of the skin by malignant cells originating from other organs. These malignant fungating wounds are difficult to treat, and they cause pain, itching and malodor. Distressing malodor imposes a major burden on patients. The carrion odor of decaying tissue is—at least in part—due to the bacterial breakdown products cadaverine and putrescine. Here, we examined the binding of cadaverine, histamine, putrescine, spermidine and spermine to the preparation of micronized purified clinoptilolite-tuff (PCT) by relying on three radiolabeled tracers ([3H]cadaverine, [3H]histamine and [3H]spermidine). Binding was rapid, stable and of high capacity. The binding affinities were in the low µM range. Displacement experiments indicated that the binding sites were non-equivalent. These three properties combined to support effective binding for any given ligand in the presence of the expected, submillimolar concentrations of competing ligands. This was further verified by measuring the binding of [3H]cadaverine in the presence of wound drainage fluids. [3H]Cadaverine was effectively adsorbed by a wound dressing, into which purified clinoptilolite-tuff had been incorporated: the observed binding capacity of this wound dressing was consistent with its content of purified clinoptilolite-tuff. Based on these findings, we propose that purified clinoptilolite-tuff be further investigated as a means to control malodor emanating from chronic wounds.

Scientia Pharmaceutica doi: 10.3390/scipharm93010006

Authors: Prasanth Thumpati Sachchida Nand Rai Chandrabhan Prajapati Kakarla Ramakrishna Santosh Kumar Singh

Novel therapies are required due to the rising cancer burden. Conventional chemotherapeutics tend to be particularly toxic, but there is a promising alternative for oncogenes, such as c-MYC. Often overexpressed in many cancer types, the potential c-MYC oncogene seems essential to the development of cancer. Targeting c-MYC protein directly was limited, but these DNA structures composed of guanine-rich sequences suppress c-MYC transcription. This review discusses recent advances in developing small compounds that selectively bind to and stabilize c-MYC G-quadruplexes (G4). These molecules have also shown promise for the inhibition of c-MYC signaling and inhibition of tumor growth, suggesting that G-quadruplex targeting could be a promising therapeutic for cancer.

Scientia Pharmaceutica doi: 10.3390/scipharm93010005

Authors: Fumiko Higashikawa Hidenori Ito Tohru Tanaka

The combination of 5-aminolevulinic acid (5-ALA) phosphate and sodium ferrous citrate (SFC) has been approved as an ingredient in dietary supplements in several countries, owing to its broad applicability in healthcare. This study aimed to assess the safety of oral administration of 5-ALA and SFC in healthy adults at doses several times higher than those commercially available. This study included 22 healthy subjects (11 males and 11 females) aged 21–59. Doses of 250 mg 5-ALA phosphate and 143.4 mg SFC (15 mg Fe) per day were administered orally for 28 days. Blood tests, urinalysis, and medical interviews were performed to assess safety. No test compound-related adverse events or abnormal changes were observed, except for elevated serum Fe levels, which were mild-to-moderate and transient. In conclusion, the combined oral administration of 5-ALA phosphate and SFC in healthy adults was safe and well-tolerated at the dose and duration investigated in this study.

Scientia Pharmaceutica doi: 10.3390/scipharm93010004

Authors: Alberto Hernández-Moreno Dania A. Nava-Tapia Miriam D. Zuñiga-Eulogio Jorge Bello-Martínez Monserrat Olea-Flores Tadeo Hernández-Moreno Mario Ordoñez Ana E. Zacapala-Gómez Miguel A. Mendoza-Catalán Napoleón Navarro-Tito

Breast cancer is the most common and the leading cause of cancer death in women worldwide; treating invasive breast carcinomas is challenging due to the side effects of chemotherapeutics. Compounds isolated from natural sources have been proposed as potential molecules for cancer therapy; for instance, the homoisoflavonoid brazilin has shown pharmacological properties, including anti-tumoral and anti-inflammatory activities. In this study, we isolated brazilin from the heartwood of Haematoxylum brasiletto; then, we performed a semi-synthesis by adding three methyl or acetyl groups to the core structure of brazilin. We confirmed the identity of brazilin and its derivatives by spectroscopic data (1H NMR and 13C NMR) and measured their purity by optical rotation. Then, we analyzed the effects of brazilin and its derivatives in three mammary gland-derived cell lines: the TNBC MDA-MB-231, the ERα(+) MCF7, and the non-tumorigenic MCF10A. We evaluated the cell viability by MTT assays, cell migration by wound-healing assays, and focal adhesion kinase (FAK) activation by Western blot. Regarding biological assays, the MTT assay showed that these compounds showed cytotoxic effects on the MCF7 and MDA-MB-231 breast cancer cells at 20 µM but was not toxic in non-tumorigenic MCF10A mammary epithelial cells. Specifically, the greatest effects found from treatment with the compounds were in the MDA-MB-231 cell line, where the IC50 of brazilin was 49.92 μM, and for MCF7, the brazilin-(OAc)3 was 49.97 μM. These effects were dose- and time-dependent, as well as being associated with a decrease in the levels of cell migration and FAK activation.

Scientia Pharmaceutica doi: 10.3390/scipharm93010003

Authors: Vasilisa A. Sukhanova Elena V. Uspenskaya Safdari Ainaz Hoang Thi Ngoc Quynh Aleksey A. Timofeev

Peptides occupy a significant share of the pharmaceutical market and are among the top-200 selling drugs in the group of non-insulin drugs with analgesic, antibacterial and cardiovascular effects. The aim of this work is to develop a comprehensive analytical approach for quality control of novel synthetic peptides with non-narcotic types of analgesia and to provide docking simulations of dermorphin complex formation at the μ-opioid receptor (MOR) binding site. The materials and methods used include the pharmaceutical substance dermorphin tetrapeptide (DMTP) (tyrosyl-D-arginyl-phenylalanyl-glycinamide); Fourier transform infrared spectroscopy (FT-IR); static and dynamic laser light scattering (DLS, LALLS); scanning optical microscopy (SEM); X-ray fluorescence elements analysis; polarimetry for optical activity determining; and Spirotox method for sample biotesting. FT-IR-Spectra indicated specific amino acid chemical groups in the tetrapeptide sequence at 3300–2700 cm−1, 1670 cm−1. UV-absorption spectra of aqueous solutions of dermorphin tetrapeptide showed an absorption maximum at 275 nm, which is in good agreement with the presented spectrum of the bovine serum albumin (BSA) standard; the Pearson’s r of calibration line “A-C%” in 0.0125% to 0.0500% concentration range is 0.999; and the calculated specific extinction value E1cm 1% = 18.38 ± 0.23. Of the 11 elements detected by X-rays, the elements copper (Cu) and cobalt (Co) have the highest X-ray intensity. Dispersion characteristics of dermorphin solutions were studied in the submicron and micron range. Conglomerates and druzes were detected by SEM, ranging in size from 2 µm to 100 µm. The specific optical activity index was calculated αD20 = +36.18 ± 2.04 [°·mL·g−1·dm−1], according to Biot’s Law. Additionally, the orientation and conformation of the dermorphin molecule in the active binding site of the 8E0G receptor were predicted using molecular modeling, revealing that the contact area affects the key amino acid residue arginine (ARG 182). This comprehensive approach to analytical methods for qualitative and quantitative analysis of dermorphin tetrapeptide can be applied in pharmacies to enhance the understanding of its biological activity and aid in the development of regulatory documentation for a new, non-narcotic analgesic based on the dermorphin tetrapeptide.

Scientia Pharmaceutica doi: 10.3390/scipharm93010002

Authors: Amar Osmanović Mirsada Salihović Elma Veljović Lamija Hindija Mirha Pazalja Maja Malenica Aida Selmanagić Selma Špirtović-Halilović

Although COVID-19 is not a pandemic anymore, the virus frequently mutates, resulting in new strains and presenting global public health challenges. The lack of oral antiviral drugs makes it difficult to treat him, which makes the creation of broadly acting antivirals necessary to fight current and next epidemics of viruses. Using the molecular docking approach, 118 compounds derived from marine organisms and 92 previously synthesized compounds were screened to assess their binding affinity for the main protease and papain-like protease enzymes of SARS-CoV-2. The best candidates from the xanthene, benzoxazole, and coumarin classes were identified. Marine-derived compounds showed slightly better potential as enzyme inhibitors, though the binding affinities of synthesized compounds were similar, with the best candidates displaying affinity values between 0.2 and 0.4 mM. Xanthenes, among both marine origin and synthesized compounds, emerged as the most promising scaffolds for further research as inhibitors. The papain-like protease was found to be more druggable than the main protease. Additionally, all top candidates met the criteria for various drug-likeness properties, indicating good oral bioavailability and low risk of adverse effects. This research provides valuable insights into the comparative affinities of marine origin and synthesized compounds from the xanthene, coumarin, and benzoxazole classes, highlighting promising candidates for further in vitro and in vivo studies.

Scientia Pharmaceutica doi: 10.3390/scipharm93010001

Authors: Manuel López-Cabanillas Lomelí Alexandra Tijerina-Sáenz David Gilberto García-Hernández Marcelo Hernández-Salazar Rogelio Salas García José Luis González-Llerena María Julia Verde-Star Anthonny Cordero-Díaz Michel Stéphane Heya

Colon cancer (CC) is the third most frequent neoplasm, with a considerably high mortality rate. Due to the side effects of conventional forms of CC treatment (surgery, chemotherapy, and radiotherapy), several studies have focused on the use of medicinal plant derivatives to provide a green therapy for CC; although phytochemicals have shown promising results against CC, translating the results obtained in vitro and in vivo to the clinical setting remains a challenge. Indeed, like other orally applied medicines, medicinal plant derivatives have to cross different physiological barriers to reach the CC microenvironment, which considerably limits their dose-dependent therapeutic efficacy. On the other hand, phytocompounds are not free from biopharmaceutical drawbacks, so novel strategies using nanoparticles (NPs) have been proposed to overcome the physiological barriers of the body and provide controlled release of actives of interest. Accordingly, the current review provides an overview and discussion on the predisposing factors to CC and conventional treatment, the use of medicinal plants in CC treatment, and the advantages provided by NPs in the treatment of CC.

Scientia Pharmaceutica doi: 10.3390/scipharm92040065

Authors: Mikhail V. Khvostov Mikhail E. Blokhin Sergey A. Borisov Vladislav V. Fomenko Yulia V. Meshkova Natalia A. Zhukova Sophia V. Nikonova Sophia V. Pavlova Maria A. Pogosova Sergey P. Medvedev Olga A. Luzina Nariman F. Salakhutdinov

Dual PPARα/γ agonists can normalize both glucose and lipid metabolism in patients with type 2 diabetes mellitus. The development of such drugs faced the detection of various toxic effects in phase III clinical trials. However, two drugs of this class managed to pass all stages of clinical trials, which makes the search for new dual PPARα/γ agonists promising. In the present study, a series of dihydrobetulonic acid amides differing in the length of the amino-alcohol linker and incorporating a pharmacophore fragment of (S)-2-ethoxy-3-phenylpropanoic acid were synthesized. The in vitro study showed that the length of the aminoalcohol linker dramatically affects the level of activation of PPAR-α and γ receptors. The synthesized compounds were tested for their ability to improve glycemic control and to counter lipid abnormalities in C57Bl/6 Ay/a mice at a dose of 30 mg/kg. Of all the compounds tested, the dihydrobetulonic acid derivative with an aminoethanol linker (15a) had the most pronounced effect in improving insulin sensitivity and glucose tolerance, and in reducing blood triglyceride levels. In addition, 15a dramatically counteracted the pathological changes in the liver, pancreas, kidney, and brown fat tissue that are characteristic of type 2 diabetes.