Scientia Pharmaceutica

18 pages, 2551 KB

Open AccessArticle

Biophysical and Computational Analysis of a Potent Antimalarial Compound Binding to Human Serum Albumin: Insights for Drug–Protein Interaction

by Kashish Azeem, Babita Aneja, Amad Uddin, Asghar Ali, Haider Thaer Abdulhameed Almuqdadi, Shailja Singh, Rajan Patel and Mohammad Abid

Sci. Pharm. 2025, 93(3), 46; https://doi.org/10.3390/scipharm93030046 - 11 Sep 2025

Abstract

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 [...] Read more.

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. Full article

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26 pages, 1549 KB

Open AccessArticle

Untargeted Metabolomic Profiling and Bioactivity Insights into Alkanna corcyrensis

by Evgenia Panou, Nikolaos Tsafantakis, Gokhan Zengin, Konstantia Graikou, Christos Ganos, Nikolas Fokialakis and Ioanna Chinou

Sci. Pharm. 2025, 93(3), 45; https://doi.org/10.3390/scipharm93030045 - 11 Sep 2025

Abstract

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 [...] Read more.

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. Full article

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17 pages, 3049 KB

Open AccessArticle

Isopimaric Acid Derivatives as Potential Dual PPARα/γ Agonists in the Treatment of Metabolic Syndrome

by 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 and Nariman F. Salakhutdinov

Sci. Pharm. 2025, 93(3), 44; https://doi.org/10.3390/scipharm93030044 - 5 Sep 2025

Viewed by 1388

Abstract

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 [...] Read more.

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/6^Ay 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. Full article

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9 pages, 826 KB

Open AccessArticle

Identification of Novel Piperidine and Pyrrolidine Derivatives as Potent Inhibitors of Pancreatic Lipase-Based Molecular Docking and In Vitro Testing

by Acharaporn Duangjai, Kwanruthai Tadpetch, Vatcharin Rukachaisirikul, Chutima S. Vaddhanaphuti and Maleeruk Utsintong

Sci. Pharm. 2025, 93(3), 43; https://doi.org/10.3390/scipharm93030043 - 29 Aug 2025

Viewed by 336

Abstract

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 ( [...] Read more.

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. Full article

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13 pages, 1407 KB

Open AccessArticle

Real-World Pilot Evaluation of a Novel Bioavailable Berberine Formulation (ToBeRock^®) in Subjects with Impaired Fasting Glucose Through Pharmacy-Based Retrospective Study

by Alessandro Colletti, Valentina Citi, Alma Martelli, Marzia Pellizzato, Enzo Riccardi and Giancarlo Cravotto

Sci. Pharm. 2025, 93(3), 42; https://doi.org/10.3390/scipharm93030042 - 29 Aug 2025

Viewed by 473

Abstract

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 [...] Read more.

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. Full article

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15 pages, 1204 KB

Open AccessReview

Pharmacological Potential of Cyperaceae Species in Experimental Models of Gastrointestinal Disorders: A Review

by José Jailson Lima Bezerra

Sci. Pharm. 2025, 93(3), 41; https://doi.org/10.3390/scipharm93030041 - 27 Aug 2025

Viewed by 398

Abstract

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 [...] Read more.

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. Full article

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16 pages, 4911 KB

Open AccessArticle

Activity of β-Caryophyllene Oxide and Benznidazole Mixture Against Trypanosoma cruzi and In Silico Prediction of Anti-Trypanocidal Interaction

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

Sci. Pharm. 2025, 93(3), 40; https://doi.org/10.3390/scipharm93030040 - 26 Aug 2025

Viewed by 1218

Abstract

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 [...] Read more.

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. Full article

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17 pages, 1850 KB

Open AccessArticle

Phytochemical Analysis and In Vitro Antibiofilm Activity of Ethanolic Leaf Extract from Quercus alnifolia Poech Against Staphylococcus aureus

by Ender Volkan, Chad Schou, Jandirk Sendker and Panagiotis Karanis

Sci. Pharm. 2025, 93(3), 39; https://doi.org/10.3390/scipharm93030039 - 25 Aug 2025

Viewed by 444

Abstract

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 [...] Read more.

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. Full article

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13 pages, 1649 KB

Open AccessArticle

Targeted Peptide-Mediated Delivery of Antisense Oligonucleotides to SMA Cells for SMN2 Gene Splicing Correction

by Marianna Maretina, Anna Egorova, Arina Il’ina, Nadezhda Krylova, Maxim Donnikov, Oleg Glotov and Anton Kiselev

Sci. Pharm. 2025, 93(3), 38; https://doi.org/10.3390/scipharm93030038 - 14 Aug 2025

Viewed by 412

Abstract

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 [...] Read more.

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. Full article

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27 pages, 11958 KB

Open AccessArticle

In Silico and In Vivo Studies Reveal the Potential Preventive Impact of Cuminum cyminum and Foeniculum vulgare Essential Oil Nanocapsules Against Depression-like States in Mice Fed a High-Fat Diet and Exposed to Chronic Unpredictable Mild Stress

by Karem Fouda and Rasha S. Mohamed

Sci. Pharm. 2025, 93(3), 37; https://doi.org/10.3390/scipharm93030037 - 14 Aug 2025

Viewed by 442

Abstract

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 [...] Read more.

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. Full article

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27 pages, 6689 KB

Open AccessArticle

Steroidal Oximes and Cervical Cancer: An In Silico Mechanistic Pathway Approach

by Carlos Antonio Sánchez-Valdeolivar, Alan Carrasco-Carballo, Jorge Organista-Nava, Jesús Sandoval-Ramírez and Berenice Illades-Aguiar

Sci. Pharm. 2025, 93(3), 36; https://doi.org/10.3390/scipharm93030036 - 4 Aug 2025

Viewed by 775

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Topic Bioinformatics in Drug Design and Discovery—2nd Edition)

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16 pages, 7856 KB

Open AccessReview

Risks of Oral Anticoagulants: Interactions with Drugs and Medicinal Plants

by Ana Sofia Martins, Cristina Monteiro and Ana Paula Duarte

Sci. Pharm. 2025, 93(3), 35; https://doi.org/10.3390/scipharm93030035 - 30 Jul 2025

Viewed by 2957

Abstract

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 [...] Read more.

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. Full article

26 pages, 685 KB

Open AccessArticle

Novel Research Regarding Topical Use of Diclofenac in Dermatology—Non-Clinical and Clinical Data

by Diana Ana-Maria Nițescu, Horia Păunescu, Mihnea Costescu, Bogdan Nițescu, Laurențiu Coman, Ion Fulga and Oana Andreia Coman

Sci. Pharm. 2025, 93(3), 34; https://doi.org/10.3390/scipharm93030034 - 30 Jul 2025

Viewed by 1026

Abstract

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 [...] Read more.

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. Full article

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12 pages, 1311 KB

Open AccessReview

Modulation of Voltage-Gated Na⁺ Channel Currents by Small Molecules: Effects on Amplitude and Gating During High-Frequency Stimulation

by Cheng-Yuan Lin, Zi-Han Gao, Chi-Wai Cheung, Edmund Cheung So and Sheng-Nan Wu

Sci. Pharm. 2025, 93(3), 33; https://doi.org/10.3390/scipharm93030033 - 24 Jul 2025

Viewed by 940

Abstract

Cumulative inhibition of voltage-gated Na⁺ channel current (I_Na) 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 I_Na during [...] Read more.

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

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14 pages, 2153 KB

Open AccessArticle

The Effect of Insulin-like Growth Factor-1 on Protein Composition and DNA Content in Damaged Somatic Nerves

by Marina Parchaykina, Milena Simakova, Tatyana Kuzmenko, Anastasia Zavarykina, Elvira Revina, Elizaveta Sadovnikova, Igor Grunyushkin, Svetlana Kiryukhina and Victor Revin

Sci. Pharm. 2025, 93(3), 32; https://doi.org/10.3390/scipharm93030032 - 22 Jul 2025

Viewed by 420

Abstract

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 [...] Read more.

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. Full article

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28 pages, 1369 KB

Open AccessReview

Expanding Horizons: Opportunities for Diclofenac Beyond Traditional Use—A Review

by Mykhailo Dronik and Maryna Stasevych

Sci. Pharm. 2025, 93(3), 31; https://doi.org/10.3390/scipharm93030031 - 16 Jul 2025

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Abstract

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 [...] Read more.

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. Full article

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24 pages, 3919 KB

Open AccessArticle

High Drug Loading of Amorphous Solid Dispersion by Hot Melt Extrusion: The Role of Magnesium Aluminometasilicate (Neusilin^® US2)

by Nithin Vidiyala, Pavani Sunkishala, Prashanth Parupathi, Preethi Mandati, Srujan Kumar Mantena, Raghu Rami Reddy Kasu and Dinesh Nyavanandi

Sci. Pharm. 2025, 93(3), 30; https://doi.org/10.3390/scipharm93030030 - 16 Jul 2025

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Abstract

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 [...] Read more.

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. Full article

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10 pages, 2360 KB

Open AccessCase Report

The New Frontier in Small-Cell Lung Cancer: Can Atezolizumab Ensure Enduring Stability?

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

Sci. Pharm. 2025, 93(3), 29; https://doi.org/10.3390/scipharm93030029 - 5 Jul 2025

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Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Monoclonal Antibodies in the Treatment of Diseases: Focus on Stability, Storage, and Administration)

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22 pages, 1889 KB

Open AccessArticle

Development and Characterization of Bigels for the Topical Delivery of Curcumin

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

Sci. Pharm. 2025, 93(3), 28; https://doi.org/10.3390/scipharm93030028 - 3 Jul 2025

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Abstract

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 [...] Read more.

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. Full article

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Sci. Pharm., Volume 93, Issue 3 (September 2025) – 19 articles

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