Scientia Pharmaceutica doi: 10.3390/scipharm92010016
Authors: Tibor Rák Adrienne Csutak
Background: Traditional and evidence-based medicines, as seen depicted throughout human history, reportedly first begin with the application of medicinal plants, animal products, or inorganic minerals as a basic framework towards effectively engineering the prototypes generally aligned to pharmaceuticals and medical nutrition. The growing global trend of complementary treatments for glaucoma can be explained by the intraocular pressure (IOP)-independent mechanisms of the disease and its interpretation as a progressive neurodegenerative disorder. Unfortunately, the categorical positions of the major fields of applied popular complementary therapies and their relation to glaucoma are consistently neglected. Methods: In consideration of bibliographic resources, the most well-known online scientific databases were searched. Conclusion: The rising popularity and the trends of products coming onto the market cannot escape the attention of pharmacists and ophthalmologists, as their patients suffering from eye diseases are also increasingly looking for such medicinal products. Most of them still lack knowledge of the appropriate evidence and side effect profiles. Our proposed systematic charts demonstrate the position of each mainstream complementary therapy throughout the applied medical sciences and are distinctively unique; we could not find any similar relevant illustration or resource among the published international literature.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010015
Authors: Bárbara Costa Isabel Silva José Carlos Oliveira Henrique Reguengo Nuno Vale
Lamotrigine, widely used for managing epilepsy and bipolar disorder, carries potential side effects, including severe anticonvulsant hypersensitivity syndrome (AHS) or drug rash with eosinophilia and systemic symptoms (DRESS), which may lead to hepatotoxicity. Patients with Type 2 Diabetes (TD2) and Non-Alcoholic Fatty Liver Disease (NAFLD) are identified as more susceptible to these adverse reactions. This exploratory analysis aims to identify clinical parameters influencing lamotrigine pharmacokinetics across diverse populations, shedding light on toxicity and therapeutic drug monitoring (TDM) considerations. Starting with a retrospective analysis of 41 lamotrigine-treated patients at Hospital Santo António reveals changes or deviations from normal levels in various blood parameters and significant correlations between these parameters. Serum level changes, including creatinine, albumin, gamma-glutamyl transferase, total bilirubin, and Vitamin B12, are observed, with strong negative correlations between Vitamin B12 and creatinine. Then, we used GastroPlus and DILIsym to explore the impact of clinical parameters on lamotrigine for different patient populations. We constructed a Physiologically Based Pharmacokinetic (PBPK) model for lamotrigine in GastroPlus, based on ADMET predictions and data from the literature, to simulate the pharmacokinetic variability of lamotrigine in different populations, and we visualized the impact of increasing lamotrigine dose on its plasma concentration–time profiles (200 mg, 400 mg, 600 mg, 1200 mg) and reduced bioavailability. At higher doses, it is possible that the saturation of metabolic pathways leads to the formation of toxic metabolites or intermediates. These metabolites may exert inhibitory effects on drug-metabolizing enzymes or disrupt normal physiological processes, thereby impeding the drug’s clearance and potentially lowering its bioavailability. In DILIsym, we investigated lamotrigine’s DILI potential for individuals with diabetes and NAFLD. The results demonstrated an increased risk, emphasizing the need for careful monitoring. This study underscores the importance of understanding lamotrigine’s pharmacokinetics for tailored treatment decisions, improved outcomes, and minimized adverse reactions.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010014
Authors: Daria S. Gordeeva Aleksandra V. Sitenkova (Bukhovets) Rouslan I. Moustafine
The aim of this study was the analysis of interpolyelectrolyte complexes (IPECs) based on Eudragit® EPO and Eudragit® L100 as prospective carriers for gastroretentive drug delivery systems (GRDDS) using two model drugs: metronidazole (MZ) and acyclovir (ACR). Eudragit® EPO/L100 IPECs with different pH concentrations were characterized by different degrees of swelling in mimicking fasted stomach medium (0.1 M HCl) and saved their shape for 6 h. The microenvironmental changes in IPEC structures in acidic medium were investigated using FT-IR spectroscopy, thermal and elemental analysis. IPEC samples showed bioadhesive properties that were not significantly different from the positive control (Carbopol) in the test with the mucin compacts. The release rate of metronidazole (class I BCS) from IPEC matrices increased with the increasing degree of swelling. IPEC 1 provided 49.62 ± 6.20% and IPEC 2 reached 87.69 ± 5.15% of metronidazole release after 6 h in mimicking fasted stomach medium (0.1 M HCl). The total amount of released acyclovir (class III BCS) from IPEC 1 was 25.76 ± 5.67% and from IPEC 2 was 21.48 ± 5.00%. Release of both drugs was controlled by relaxation of polymeric chains in matrices according to the Peppas–Sahlin model. According to the received results, investigated interpolymer complexes are prospects for further evaluation as carriers for gastroretentive bioadhesive systems.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010013
Authors: Eun Bok Baek Eun-Ju Hong Jung-Hee Kim Min Kim Jongmin Ahn Hyo-Jung Kwun
Benign prostatic hyperplasia (BPH) is a common disease in aging men. Panicum dichotomiflorum (PD) is an annual grass species of Poaceae that is distributed worldwide. The present study examined whether PD has a protective effect against BPH. BPH was generated in rats by daily subcutaneous administration of testosterone for four weeks. During this period, the rats were also given daily oral gavages of an extract of PD (150 mg/kg). After the final treatment, all animals were euthanized and their prostates were collected and weighed. In BPH model rats, the prostate weight and levels of dihydrotestosterone (DHT) and 5α-reductase expression were inhibited following treatment with PD extract. Testosterone-induced increases in prostate gland epithelial thickness and expression of cyclin D1 and proliferating cell nuclear antigen (PCNA) were markedly suppressed in PD-treated rats, whereas cleaved caspase-3 levels were increased. PD administration also decreased the expression of transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF), the phosphorylation of Akt, and inflammatory cytokines levels. Taken together, these results show that PD extract protects against testosterone-induced BPH progression by alleviating prostate cell growth and reducing levels of growth factors and inflammatory cytokines, indicating that PD extract may have potential in protecting against BPH.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010012
Authors: Sergio Adrian Ocampo-Ortega Sandra Edith Cabrera-Becerra Vivany Maydel Sierra-Sanchez Vanessa Giselle García-Rubio Citlali Margarita Blancas-Napoles Rodrigo Romero-Nava Fengyang Huang Enrique Hong Asdrúbal Aguilera-Méndez Santiago Villafaña
Chronic obstructive pulmonary disease (COPD), characterised by persistent airflow limitation during breathing, is considered to be the third leading cause of death worldwide. Among the mechanisms involved in this pathology is the excessive generation of neutrophil extracellular traps (NETs), which can induce an unwanted inflammatory response. These traps have been reported to be generated by the enzyme peptidyl arginine deiminase 4 (PAD4). The aim of this work is therefore to evaluate the effect of the administration of a siRNA targeting PAD4 on lung damage in a COPD animal model. Wistar rats weighing 300–350 g were administered cadmium chloride (5 mg/kg i.p.) every 24 h. Then, following one week of the administration of cadmium chloride, the PAD4-targeted siRNA was administered, and at the second week, lung function was measured, as were lung and heart weights, as well as PAD4 expression by RT-PCR. Our results showed that cadmium administration generated a COPD model, which increased PAD4 expression and decreased lung and heart weights and respiratory function. SiRNA administration partially reversed the changes associated with the COPD model. In conclusion, our results suggest that administration of an siRNA targeting PAD4 could improve respiratory function by decreasing lung and heart damage.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010011
Authors: Tomasz Zaprutko Józefina Sprawka Barbara Maciuszek-Bartkowska Piotr Ratajczak Dorota Kopciuch Anna Paczkowska Krzysztof Kus
Pharmacists play an important role, being increasingly focused on patient care and pharmaceutical services. This trend is also noticeable in Poland. Thus, we aimed to study the opinions of Polish pharmacists to determine the potential for introducing a new category of pharmacist-only medicines (POMs). This study was conducted during the COVID-19 pandemic. Hence, the survey (anonymous questionnaire consisting of 10 questions addressed to pharmacists) was only available in electronic form. A total of 500 correctly completed surveys were collected and subjected to further analysis. The vast majority of pharmacists (91.8%) revealed a willingness to expand their professional rights and 88% stated that the POMs implementation would be important. As a substance that should function as a POM instead of an OTC medicine, respondents most often indicated ketoprofen, sildenafil, and mometasone, accounting for 26.2%, 24.8%, and 24.4% of responses, respectively. In terms of funding pharmaceutical services, 54.2% of respondents indicated that costs should be covered partially by the patient and the payer. There is a clear need for the incorporation of the POM category in Poland. Polish pharmacists are anticipating the development of pharmaceutical services which should be partly covered by patients and payers.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010010
Authors: Kamila Bartoníková Miroslava Špaglová Martina Papadakos Michal Hanko Oliver Macho
(1) Background: The study aimed to compare the impact of various natural polymers–sodium alginate, acacia gum, carrageenan, guar gum, xanthan gum, and tragacanth on the formulation and the physical properties of mucoadhesive vaginal tablets containing metronidazole (167 mg/g). (2) Methods: The quality of the tablets prepared by direct compression was evaluated by pharmacopoeia tests (uniformity of mass, resistance to crushing, friability). Mucoadhesion of the tablets was characterized by swelling capacity and mucoadhesive strength, i.e., the force required to detach the tablet from the rabbit mucosa. In vitro drug release was performed by a modified dissolution method in paddle apparatus containing the simulated vaginal fluid (pH 4.5). Scanning electron microscopy observed morphological changes on the swollen tablets’ surface. (3) Results: Pharmacopoeia tests have shown that all prepared tablets met the requirements on quality. The highest mucoadhesive strength was noted in tablets containing guar and xanthan gum. The highest swelling capacity was possessed by tablets containing carrageenan. (4) Conclusions: Summarizing all tests’ results, sodium alginate can be considered the most suitable natural polymer in tablet formulation. The combination of polymers providing higher mucoadhesiveness and at the same time a prolonged release, e.g., xanthan or guar, together with sodium alginate, could also be of interest.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010009
Authors: Carlos Enrique López-Luna Cruz Vargas-De-León Rocio Alejandra Gutiérrez-Rojas Karla Aidee Aguayo-Cerón Claudia Camelia Calzada-Mendoza Fengyang Huang Rodrigo Romero-Nava Maria Esther Ocharan-Hernandez
Zoapatle, a native plant utilized for centuries in traditional Mexican medicine, is abundantly found in Mesoamerica and northern South America. Pleiotropic effects of this genus have been recognized, primarily inducing alterations in smooth muscle contractility in animal models. The aim of this study was to evaluate the effect of Zoapatle on the hypertrophy index and the gene expression of TNF-α, IL-1β, NF-κB, STAT5, and the PRLR in the brain, left ventricle, and renal cortex of rats with isoproterenol-induced cardiac hypertrophy. Three groups were studied, the control group (n = 4), hypertrophy group (n = 4) and hypertrophy group treated with Zoapatle (n = 4). A ventricular hypertrophy model was developed with 150 mg/kg/day of isoproterenol intraperitoneally administered over two days with a 24 h interval between applications. Zoapatle was administered for 28 consecutive days (25 mg/kg). Gene expression was determined with RT-qPCR. Subsequently, a principal component analysis (PCA) was performed using the RNA expression variables. A notably reduced left ventricle mass index was observed in the Zoapatle group. Additionally, Zoapatle administration in cardiac hypertrophy demonstrated a significant decrease in the gene expression of TNF-α, IL-1B, STAT 5, and the PRLR. TNF-α and the transcription factor STAT5 exhibited a similar trend in both the left ventricle and renal cortex, suggesting a correlation with the inflammatory state in these tissues due to ventricular hypertrophy. The findings suggest that Zoapatle reverses the hypertrophy index in a hypertrophy model, concurrently reducing several proinflammatory mediators associated with the hypertrophy index.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010008
Authors: Georgios Agapakis Angeliki Siamidi Stefanos Kikionis Marilena Vlachou Natassa Pippa
The design, development, and release kinetics of omeprazole (OME) from solid dosage forms have been investigated. These formulations were examined for their resilience in pH = 4.5 buffer solutions and their rate of disintegration in a small-intestine-like environment (pH = 6.8). The results were compared with those of the well-known brand product Losec®, where its use is accompanied by numerous benefits but drawbacks as well. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) tests were conducted in order to examine the release kinetics of the various dosage forms and provide explanations based on the interactions between the excipients and the active substance.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010007
Authors: Bianca-Eugenia Ősz Ruxandra Ștefănescu Andreea Sălcudean George Jîtcă Camil-Eugen Vari
Easy access to over-the-counter (OTC) drugs makes it possible to procure active substances that normally used in therapeutic doses do not raise health problems. The use of high doses of OTC drugs containing codeine, loperamide, pseudoephedrine, diphenhydramine or dimenhydrinate, as well as the use of benzidamine systemically raises concerns regarding the increase in units sold. These drugs are used for recreational or euphorizing purposes, including by young women of childbearing age, psychoactive substance users representing a risk group in terms of the possibility of an unplanned pregnancy. Abusive consumption of OTC products during pregnancy is harmful, with consequences for both fetal and late development that can occur in the infant. This literature review presents the risks (teratogenicity, fetal toxicity, neonatal abstinence syndrome, etc.) associated with the use of potentially psychoactive OTC drugs to emphasize the importance of re-evaluating OTC classification and dispensing.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010006
Authors: Sahena Ferdosh
Calophyllum inophyllum L. has been used for many generations by Pacific Islanders because of its numerous health and aesthetic advantages. The leaves, stems, roots, fruits, flowers, and seeds of this plant contain significant phytochemicals, including flavonoids, coumarins, fatty acids, and xanthones, which have been shown to have wound healing, analgesic, anti-inflammatory, antiaging, anti-arthritic, anti-cancer, anti-proliferative, anti-diabetic, anti-microbial, and anti-HIV effects. The chemical profiles and bioactive potential may vary due to different extraction techniques, plant parts, and geographical origins. Extraction is the essential first step in the analysis of bioactive compounds that leads to further separation, identification, and characterization. Conventional methods like maceration, Soxhlet, and percolation are often used to extract bioactive compounds from C. inophyllum. However, little study has been carried out on non-conventional methods such as pressured liquid extraction, supercritical fluid extraction (SFE), and ultrasound-assisted extraction. The SFE method can be used to extract bioactive compounds from C. inophyllum to retain their pharmacological properties for application in pharmaceutical and cosmetic products.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010005
Authors: Roman P. Terekhov Evgeny S. Melnikov Ilya D. Nikitin Margarita A. Tokareva Tatyana A. Rodina Anastasiya D. Savina Denis I. Pankov Anastasiya K. Zhevlakova Vladimir L. Beloborodov Irina A. Selivanova
Taxifolin is a natural polyphenol belonging to the class of flavonoids. The structure of this compound is characterized by the presence of two chiral centers. The spheroidal form of taxifolin (TAXs) has emerged as a promising modification due to enhanced solubility, higher safety profile, and long-term release from solid dosage forms. The study’s objective was to assess the diastereomeric content in TAXs and industrially produced samples of taxifolin. Considering the difference in the physico-chemical properties of diastereomers and based on the literature data, we developed a qualitative HPLC method. The chromatograms were recorded using a diode array detector at 290 nm and a mass spectrometer operated in negative ionization mode. Our data suggest that a biphenyl column and gradient elution using 0.1% formic acid in water and 0.2% formic acid in methanol, with the organic phase gradient from 7% to 21% and a flow rate of 0.65 mL/min for 15 min at 60 °C, provides the best conditions for the separation of taxifolin diastereomers. This method was validated for quantitative analysis. We discovered that the cis-isomer was present in all the analyzed samples, with its quantity ranging from 0.8% to 9.5%. TAXs can be considered a sample enriched with diastereomers.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010004
Authors: Anna Nowak Paula Ossowicz-Rupniewska Maciej Konopacki Anna Muzykiewicz-Szymańska Łukasz Kucharski Rafał Rakoczy
This study introduces a novel approach for enhancing the transdermal permeability of ibuprofen through the skin by utilising a rotating magnetic field (RMF). The core objective is to systematically evaluate the influence of a 50 Hz RMF on ibuprofen’s skin permeability across various formulation types, each employing distinct physical forms and excipients. The experimental setup involved Franz cells with skin as the membrane, exposed to a 50 Hz RMF in conjunction with specific formulations. Subsequent comprehensive analysis revealed a notable increase in the transdermal transport of ibuprofen, irrespective of the formulation employed. Notably, the differences in the initial 30 min of permeation were particularly pronounced. Crucially, this investigation establishes that the application of a 50 Hz RMF resulted in a remarkable over-sevenfold increase in ibuprofen permeability compared to the control group without RMF exposure. It is noteworthy that in all semi-solid pharmaceutical formulations tested, RMF effectively reduced the delay time to zero, underscoring the efficiency of RMF in overcoming barriers to transdermal drug delivery. This research positions the application of RMF as a highly promising and innovative technology, significantly enhancing the transdermal penetration of anti-inflammatory and analgesic drugs through the skin. The demonstrated effectiveness of RMF across diverse formulations suggests its potential in transdermal drug delivery, offering a novel and efficient strategy for improving therapeutic outcomes in the administration of ibuprofen and potentially other pharmaceutical agents.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010003
Authors: Chang-Eui Hong Su-Yun Lyu
Atopic dermatitis (AD) is increasingly prevalent globally. However, the frequent and prolonged use of corticosteroids, which are commonly employed for AD treatment, carries potential side effects. Korean mistletoe (Viscum album L. var. coloratum), a perennial parasitic plant, has demonstrated various biological effects. In this study, we conducted in vivo investigations to determine whether Korean mistletoe possesses anti-inflammatory effects that play pivotal roles in regulating the pathological mechanisms of AD. BALB/c mice with AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) were utilized to explore the therapeutic effects of 1% and 2% Korean mistletoe extract (KME) ointments. The KME ointment was topically applied to the dorsal surface of the BALB/c mice, and they were categorized into four distinct groups: normal, DNCB-induced, DNCB-induced with 1% KME ointment, and DNCB-induced with 2% KME ointment. Each assessment parameter employed to evaluate the curative impact of the KME ointment displayed improvement with the application of the 1% KME ointment. While the effects observed were less pronounced than those of the 1% KME ointment, the overall therapeutic outcomes were also evident with the utilization of the 2% KME ointment. The results suggest the potential of Korean mistletoe as a viable therapeutic agent for AD. Further investigations are warranted to elucidate the underlying mechanisms of action.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010002
Authors: Ana Marcela Arrieta Gómez María Antonia Díaz-Mendoza Yesit Bello Lemus Grethel León-Mejía Martha Lucia Ruiz Benitez
The aim of this study was to establish the relationship between different polymorphisms in drug transporter and metabolizer genes and resistance to imatinib in chronic myeloid leukemia (CML). For this purpose, an exhaustive search was carried out in the Scopus, Web of Science, and PubMed databases using different combinations of keywords with different inclusion and exclusion criteria. The meta-analysis included nine studies that met the established criteria. The results of the study showed that the polymorphic variants AG and GG of CYP3A5*3 are associated with response to treatment, presenting a significantly lower risk with resistance to imatinib. Likewise, the variants T1236C and G2677T/A of the ABCB1 gene show a significant association with treatment efficacy. In addition, the genetic polymorphism 1236T, homozygous CC of the MDR1 gene, significantly influences the increased risk of cytogenetic relapse and the polymorphic variant 361G>A GA of the SLCO1A2 gene significantly affects the complete molecular response.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm92010001
Authors: Elena V. Uspenskaya Vasilisa A. Sukhanova Ekaterina S. Kuzmina Tatyana V. Pleteneva Olga V. Levitskaya Timur M. Garaev Anton V. Syroeshkin
The need for new antimicrobial agents (AntAg) is driven by the persistent antibiotic resistance in microorganisms, as well as the increasing frequency of pandemics. Due to the deficiency of AntAg, research aimed at developing speedy approaches to find new drug candidates is relevant. This study aims to conduct an in silico study of the biological activity spectrum as well as the molecular binding mechanisms of four structurally different forms of levofloxacin (Lvf) with bacterial topoisomerases targets of type IIA (DNA gyrase and topoisomerase IV) to enable the development of drugs with an improved characterization of the safety profile. To achieve this goal, a number of software products were used, such as ChemicPen v. 2.6, PyMol 2.5, Avogadro 1.2.0, PASS, AutoDockTools 1.5.7 with the new generation software Autodock Vina. These software products are the first to be made available for visualization of clusters with determination of ligand-receptor pair binding affinity, as well as clustering coordinates and proposed mechanisms of action. One of the real structures of Lvf, a decarboxylated derivative, was obtained with tribochemical (TrbCh) exposure. The action spectrum of molecular ligands is described based on a Bayesian probability activity prediction model (PASS software Version 2.0). Predicted and real (PMS and RMS) molecular structures of Lvf, with decreasing levels of structural complexity, were translated into descriptors via Wiener (W), Balaban (Vs), Detour (Ip), and Electropy € indices. The 2D «structure-activity» diagrams were used to differentiate closely related structures of levofloxacin. PMS and RMS were visualized as 3D models of the ligand-receptor complexes. The contact regions of RMS and PMS with key amino acid residues—SER-79, DT-15, DG-1, DA-1—were demonstrated. The intra- and inter-molecular binding sites, data on free energy (affinity values, kcal/mol), the binding constant Kb (M−1), and the number of clusters are presented. The research results obtained from the presented in silico approach to explore the spectrum of action find quantitative “structure-activity” correlations, and predict molecular mechanisms may be of applied interest for directed drug discovery.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040056
Authors: Eun-Jae Park Hee Ju Lim Hyung Jin Lim Bong-Sik Yun Soyoung Lee Seung-Jae Lee Seung Woong Lee
Lindera obtusiloba Blume has several activities, such as anti-inflammatory, anti-allergic, anti-tumor, anti-wrinkle, and antioxidant activities. Interleukin-6 (IL-6) is a classic pro-inflammatory cytokine that is associated with various functions, such as proliferation, invasion, inflammatory responses and functions within antioxidant defense systems. In this study, we investigated IL-6-induced STAT3 activation of lignan compounds isolated from L. obtusiloba. The structures of the isolated compounds were elucidated via spectroscopic nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS). As a result, seven lignans were identified from L. obtusiloba. All the isolated compounds (1–7) were evaluated for their IL-6-induced STAT3 inhibitory effects in Hep3B cells using a luciferase reporter assay. Of the isolates, compounds 1 and 5 showed inhibitory effects against IL-6-stimulated STAT3 activation. Furthermore, the mRNA expression levels of inflammation-related genes such as CRP, IL-1b, and SOCS3 were significantly reduced by exposure to compounds 1 and 5. The protein levels of p-STAT3 and p-JAK2 in IL-6-induced U266 cells were regulated in the presence of lignans derived from Lindera obtusiloba by Western blot assay. Based on the results, this study of L. obtusiloba demonstrates that the species has promise as a bioactive candidate for the treatment of IL-6-induced STAT3-related disease.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040055
Authors: Rosa Edith Grijalva-Guiza Thais Lucía Grijalva-Montano Mariana Cuautle Enrique Quiroga-González Luis Ricardo Hernández Alicia Ortega Aguilar Aura Matilde Jiménez-Garduño
Flavonoids are plant-secondary metabolites with cardiovascular protective properties. Few studies have examined specific flavonoid classes or pure flavonoids concerning some common cardiovascular risks. To obtain information in a systematic review to analyze in a meta-analysis, data were recovered regarding flavonoid intake in random controlled trials and atherosclerosis disease, related to risk factors such as blood pressure, total cholesterol (TC), and low-density lipoprotein cholesterol (LDLc). Our aim was to conduct a meta-analysis using the Scopus and PubMed databases without restrictions on the year of publication, extracting articles over the period 1–15 April 2023, searching for randomized controlled trials (RCTs) that investigated different types of flavonoids, measuring blood pressure and low-density cholesterol plasmatic concentration. This paper’s Prospero registration is CRD 42023414153. There were 19 RCTs: twelve RCTs were considered for blood pressure data analysis and fifteen RCTs for total cholesterol and LDL cholesterol data analysis. The meta-analysis showed no significant differences between placebo treatments and treatments with different flavonoids on blood pressure. However, there was a significant difference found in quantitative analysis for TC and LDLc. In conclusion, flavonoid consumption can be associated with a lower risk of LDLc and TC, and more RCTs are needed to specify the effect of more types of pure flavonoids in atherosclerotic patients.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040054
Authors: Laura Fernanda Neira Julio Cesar Mantilla Patricia Escobar
A study was conducted on BALB/c mice infected with Leishmania (Leishmania) amazonensis to analyse the effects of 0.5% miltefosine (MTF) hydrogel treatment on cutaneous leishmaniasis (CL) lesions. The mice were treated for 25 days topically, and lesion sizes, parasite loads, histopathology, ultrastructure, cytokines including interleukin 4 (IL-4), tumour necrosis factor alfa (TNFα), interferon gamma (IFNγ), IL-10, and vascular endothelial growth factor (VEGF) profiles were evaluated on days 0, 12, 25, and 85. After 12 days of treatment, the lesion sizes and parasite numbers decreased. By day 60 post treatment, there were no lesions and only a few parasites. At day 25, there was a temporary papillomatosis reaction, an increase in mast cells, a few giant cells, and granulomas, and a decrease in diffuse inflammatory infiltrate and parasites. Transmission electron microscopy (TEM) examination showed early ultrastructural changes, including macrophages without parasites and vacuoles containing electrodense material. At the different evaluated times, the cytokine regulation indexes (ICRs) decreased for IL-4, TNFα, and VEGF. According to the study, the 0.5% MTF hydrogel was effective and showed positive results from the early stages of usage. The MTF directly targeted parasites, downregulated the release of IL-4, TNFα, and VEGF, increased mast cell production, and induced granuloma reaction during evaluation periods.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040053
Authors: Saverio Nucera Rosa Maria Bulotta Stefano Ruga Rosamaria Caminiti Maria Serra Roberto Bava Fabio Castagna Carmine Lupia Mariangela Marrelli Filomena Conforti Giancarlo Statti Vincenzo Mollace Ernesto Palma
Plants are an untapped natural resource; their secondary metabolites take part in a variety of pharmacological activities, making them an essential ingredient in the synthesis of novel medications and the source of reserve resources in this process. Hepatitis and liver cancer are two conditions that can result from non-alcoholic fatty liver disease (NAFLD). NAFLD is a condition that now affects a significant section of the global population. There is a need for preventative action on predisposing factors. Due to their effectiveness and few side effects, herbal medications are frequently utilized for the prevention and treatment of NAFLD. This review discusses the pathogenetic processes of NAFLD and the evidence brought to support the potential of botanical species and their derivatives in limiting the causes that predispose to the onset of NAFLD.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040052
Authors: Vanessa Giselle Garcia-Rubio Sandra Edith Cabrera-Becerra Sergio Adrian Ocampo-Ortega Citlali Margarita Blancas-Napoles Vivany Maydel Sierra-Sánchez Rodrigo Romero-Nava Rocío Alejandra Gutiérrez-Rojas Fengyang Huang Enrique Hong Santiago Villafaña
Diabetes mellitus is a metabolic disease that can produce different alterations such as endothelial dysfunction, which is defined as a decrease in the vasodilator responses of the mechanisms involved such as the nitric oxide (NO) pathway. The overexpression of PDE5A has been reported in diabetes, which causes an increase in the hydrolysis of cGMP and a decrease in the NO pathway. For this reason, the aim of this study was to evaluate whether siRNAs targeting PDE5A can reduce the endothelial dysfunction associated with diabetes. We used male Wistar rats (200–250 g) that were administered streptozotocin (STZ) (60 mg/kg i.p) to induce diabetes. Two weeks after STZ administration, the siRNAs or vehicle were administered and then, at 4 weeks, dose–response curves to acetylcholine were performed and PDE5A mRNA levels were measured by RT-PCR. siRNAs were designed by the bioinformatic analysis of human–rat FASTA sequences and synthesised in the Mermade-8 equipment. Our results showed that 4 weeks of diabetes produces a decrease in the vasodilator responses to acetylcholine and an increase in the expression of PDE5A mRNA, while the administration of siRNAs partially restores the vasodilator response and decreases PDE5A expression. We conclude that the administration of siRNAs targeting PDE5A partially reverts the endothelial impairment associated with diabetes.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040051
Authors: Alba Alonso Llorente Josefa Salgado Garrido Oscar Teijido Hermida Fabricio González Andrade Alberto Valiente Martín Ana Fanlo Villacampa Jorge Vicente Romero
CYP2C19 is a highly polymorphic gene responsible for the metabolism of commonly used drugs. CYP2C19*1, the wild-type allele, is associated with normal enzyme activity, whereas CYP2C19*2 and CYP2C19*17 lead to null and increased enzyme activity, respectively. The use of different instruments to perform the same pharmacogenetic tests should not affect the reliability of the results reported to clinicians, as required by the ISO 15189 standard. Genotyping assays allowed for the identification of gene variants corresponding to the CYP2C19*2 and CYP2C19*17 haplotypes in 44 selected samples. Each sample was analyzed in duplicate using the Thermo Fisher Taqman Drug Metabolism probes CYP2C19*2: c_25986767_70 (rs4244285) and CYP2C19*17: c_469857_10 (rs12248560). The experiments were performed on two widely used types of real-time PCR analyzers: ABI PRSIM™7500 and QuantStudioTM12KFlex (both from Applied Biosystems, Thermofisher). The data were analyzed in a Thermo Fisher Cloud facility. The analysis was performed independently by two qualified professionals. Both different instruments and analysts’ interpretations were consistent in identifying the native homozygous, heterozygous, and mutant homozygous variants for CYP2C19*2 and CYP2C19*17. The results provided by both the primary and backup analyzers showed a perfect correlation. This would allow for the use of the backup analyzer in case the main one is not available.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040050
Authors: Wilson Leonardo Villarreal Romero Jorge Eliecer Robles Camargo Geison Modesti Costa
Kalanchoe pinnata is a species widely used in traditional medicine in Latin America and southern Africa. This species has been reported to have different activities, such as antioxidant, anti-inflammatory, and cytotoxic, the latter being related to its flavonoid content. The aim of this study was to contribute to the standardization of the aqueous extract of flowers from Kalanchoe pinnata. Purification of chemical markers was carried out by centrifugal partition chromatography (CPC). Stability tests under stress conditions were conducted for the extract by using the chromatographic profiles analyzed by ultra-performance liquid chromatography coupled to photodiode array detection (UPLC-PDA) and ultra-high-performance liquid chromatography combined with quadrupole-time of flight–mass spectrometry (UHPLC-MS-QTOF), with quantification of flavonoids by a validated UPLC-PDA method. Physicochemical variables of the plant material were within the limits established by official guides. Thirteen flavonoids present in the extract were identified, the major compounds being quercetin 3-O-α-L-arabinopyranosyl-(1→2)-α-L-rhamnopyranoside and quercetin 3-O-D-glucuronide, purified by CPC. A range of total flavonoids for the extract from 8–13% was determined. Finally, through stability tests, it was observed that the extract was stable in most conditions but evidenced moderate degradations upon acid and basic hydrolysis. Through qualitative and quantitative chemical characterizations, it was possible to chemically standardize the aqueous extract of flowers from K. pinnata, with a high content of flavonoids, under parameters required by the WHO and pharmacopoeias.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040049
Authors: Kevin P. Lévuok-Mena Oscar J. Patiño-Ladino Juliet A. Prieto-Rodríguez
Plant-based therapies are widely utilized for treating diseases in approximately 80% of the global population, including Colombia’s Chocó Department. This study aimed to identify and evaluate plants with significant therapeutic value for obesity and diabetes in Chocó. The inhibitory effects of these plants on pancreatic lipase (PL), α-glucosidase (AG), and α-amylase (AA) were assessed, and the most promising species were selected to isolate and identify bioactive components. Artocarpus altilis, Momordica balsamina, Bauhinia picta, Neurolaena lobata, and Vismia macrophylla emerged as key species based on their traditional usage among the Chocó population. Notably, the extract derived from Vismia macrophylla demonstrated the most encouraging outcomes as a digestive enzyme inhibitor, exhibiting IC50 values of 0.99 ± 0.21 μg/mL, 5.61 ± 0.82 mg/mL, and 28.91 ± 2.10 μg/mL for AG, AA, and PL, respectively. Further chemical analysis led to the isolation of three bioactive compounds: 5′-demethoxycadensin G 1, para-hydroxybenzoic acid methyl ester 2, and para-hydroxybenzoic acid butyl ester 3. Compound 1 displayed the highest activity against AG (IC50 = 164.30 ± 0.11 μM), while compounds 2 (IC50 = 28.50 ± 4.07 μM) and 3 (IC50 = 10.15 ± 3.42 μM) exhibited potent inhibitory effects on PL. Molecular docking and enzymatic kinetics studies indicate that these bioactive compounds primarily act as mixed inhibitors of AG and non-competitive inhibitors of PL. These findings underscore the potential of V. macrophylla and its compounds as effective inhibitors of digestive enzymes associated with obesity and type 2 diabetes.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040048
Authors: Wan-Taek Lim Chang-Eui Hong Su-Yun Lyu
Korean mistletoe (Viscum album var. coloratum) has been traditionally used as a remedy for cancer, diabetes, and hypertension. This study investigated the immuno-modulatory effects of Korean mistletoe water extract, specifically on MDA-MB-231 cells, a highly metastatic breast cancer cell line, when co-cultured with THP-1 human macrophage cells. When compared to MDA-MB-231 cells cultured alone, the co-culture of MDA-MB-231/THP-1 cells treated with mistletoe extract showed a significant reduction in IL-6 secretion. Additionally, these co-cultures exhibited elevated levels of IL-4, TGF-β, and IFN-y. These results suggest that water extracts from mistletoe have the potential to induce mitochondria-targeted apoptosis in MDA-MB 231 cells stimulated by THP macrophages. Regarding apoptosis, in MDA-MB-231 cells co-cultured with THP-1 macrophages, mistletoe water extract treatment triggered a significant increase in Bax/Bcl-2 ratio, caspase-3 activation, and PARP inactivation. In addition, there was a significant increase in E-cadherin and a decrease in N-cadherin. Treatment of Korean mistletoe also led to significant reductions in both MMP-2 and -9. Furthermore, inhibition of cell migration in MDA-MB-231/THP-1 co-cultured cells was observed. In summary, this study highlights the potential of Korean mistletoe as a prospective drug for the treatment of triple-negative breast cancer, particularly through its ability to regulate human immunity.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040047
Authors: Dante Avilés-Montes David Osvaldo Salinas-Sánchez César Sotelo-Leyva Alejandro Zamilpa Franceli Itzel Batalla-Martinez Rodolfo Abarca-Vargas Juan Manuel Rivas-González Óscar Dorado Rodolfo Figueroa-Brito Vera L. Petricevich Dulce Lourdes Morales-Ferra Manasés González-Cortazar
Mental and neurological disorders are conditions that affect thoughts, emotions, behavior, and relationships. Malpighia mexicana A. Juss. is a plant used in Mexican traditional medicine for the treatment of such disorders. This work aimed to investigate the antidepressant, anxiolytic, sedative, hypnotic, and anticonvulsant effects of the acetonic extract (MmAE) of M. mexicana and its fractions (F3, F4-10, F14) using the forced swimming test (FST), elevated plus maze (EPM), open field test (OFT), pentobarbital-induced sleep test (PBTt), and pentylenetetrazol-induced seizure test (PTZt). MmAE, F3, F4-10, F14, and vehicle were administrated orally 24, 18, and 1 h prior to the evaluations. Imipramine (15 mg/kg, p.o.) was administrated 1 h prior to the evaluations as a positive control for the FST, while diazepam (1 mg/kg, p.o.) was administrated 1 h prior to the evaluations as a positive control for the EPM, OFT, PBTt, and PTZt. MmAE had an anxiolytic effect; MmAE and F3, F4-10, and F14 showed an antidepressant effect, sedative effect, hypnotic effect, and anticonvulsant effect. Using HPLC, we identified the compounds quercetin 3-O-rutinoside (1), kaempferol 3-O-glucoside (2), luteolin 7-O-glucoside (3), quercetin (4), and kaempferol (5) in MmAE and compounds (1), (2), and (3) in F14. Using GC-MS, we identified α-tocopherol, phytol, and β-amyrin in F3; β-tocopherol, phytol, β-sitosterol, and β-amyrin in F4-10; and α- tocopherol, phytol, β-sitosterol, and β-amyrin in F4-10. The neuropharmacological effects found in this work may be due to the presence of vitamins, phytosterols, terpenes, and flavonoids. This research requires further study to clarify the mechanisms of action of the identified compounds.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040046
Authors: Jesús Alfredo Araujo-León Maira Rubi Segura-Campos Rolffy Ortiz-Andrade Priscila Vazquez-Garcia Daniela Carvajal-Sánchez Ángel Cabañas-Wuan Avel Adolfo González-Sánchez Jonatan Uuh-Narvaez Juan Carlos Sánchez-Salgado Inés Fuentes-Noriega Zhelmy Martín-Quintal
Diabetes is one of the most prevalent diseases worldwide, and the search for therapeutic alternatives in developing countries has been focused on natural products, primarily from plants. This study evaluated the antihyperglycemic and hypoglycemic activities of the albedo (FA) and flavedo (FF) flavonoid fractions obtained from orange peels (often discarded) in normoglycemic Wistar rats. The flavonoid fractions were identified and quantified using HPLC-UV-DAD and compared with glibenclamide, repaglinide, saxagliptin, and acarbose. Additionally, both fractions were tested in a streptozotocin (65 mg/kg)/nicotinamide (100 mg/kg)-induced diabetic model. In normoglycemic rats, the highest glucose variation (%VG) occurred during the first hour after FA (112.8%) and FF (105.30%) administration at 100 mg/kg, indicating a hypoglycemic effect. In diabetic rats, FF at 100 mg/kg showed the highest %VG (140.41%) during the first hour after administration. HPLC-UV-DAD analysis revealed the presence of hesperidin (HSP) and naringenin (NGN), with the highest concentrations found in FA (HSP: 41.41%; NGN: 10.75%). These findings suggest potential antihyperglycemic effects of FA and FF fractions, possibly attributed to the presence of HSP and NGN. The results obtained in this work lay the foundations to explore the therapeutic applications of orange peels for controlling hyperglycemia in diabetes. In conclusion, our results suggest a reevaluation and revalorization of orange peels, as they contain pharmaceutically relevant flavonoids.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91040045
Authors: Maria A. Konnova Alexander A. Volkov Anna G. Solovyeva Peter V. Peretyagin Nina B. Melnikova
The formulation of the transdermal patch with fulvic acid (FA) on an emulsion basis using pluronic Kolliphor® p237 as a permeability enhancer was developed and studied for anti-inflammatory properties. FA was isolated from the peat in the Nizhny Novgorod region of Russia and characterized as a potential active pharmaceutical ingredient. In vitro studies of the release of FA from the transdermal patch, as well as the FA penetration through the acetyl cellulose membrane using the Franz diffusion cell, showed its high efficiency (56% and 90%, respectively, in 8 h). In the in vivo experiment, qualitative and quantitative features of the rat knee caused by complete Freund’s adjuvant-induced arthritis (morphological changes, the FA influence on the biochemical indexes) were studied. The inflammatory process that developed within 15 days was accompanied by the activation of antioxidant oxidoreductase enzymes (by 50–70%), the increase in the cross-sectional diameter of the cartilage, and the increase in the values of marker indicators of the process of rheumatoid arthritis. Within 7 days of treatment, under the influence of FA, the values of ESR, RF, leukocytes, C-reactive protein, as well as the biochemical parameters characterizing oxidative stress (SOD, catalase, glutathione reductase, LDH, G6PD) normalized, and the edema reduced. These results may be useful for arthritis treatment using the transdermal patch with FA.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030044
Authors: Ibrahim S. Al Nasr Waleed S. Koko Tariq A. Khan Rainer Schobert Bernhard Biersack
Miscellaneous imines and acyl hydrazones were prepared from 5-nitrofuraldehyde and 5-nitrothiophene-2-carboxaldehyde. Their activities against Toxoplasma gondii and Leishmania major parasites were evaluated. Promising antiparasitic effects and selectivities were observed for certain acyl hydrazones and imines. Cobalt(II) and copper(II) complexes conserved the high anti-Toxoplasma activities of 3-hydroxy-2-naphthoic carboxyl hydrazone (2a). In addition, sound activities against L. major promastigotes were observed for various analogs of 2a (2b and 2i) and pyrid-2-ylpyrazole-based imines (3g and 3h). Relatively low toxicities to kidney cells and macrophages indicate promising selectivity profiles for these compounds.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030043
Authors: Sahena Ferdosh
The Chamorro healers of Guam have more than a thousand years of history of using herbs and medicinal plants for the treatment of common ailments. The objective of this study is to review the bioactive compounds and pharmacological properties of medicinal plants which are used for urinary tract health by local healers. Literature searches were performed using Google Scholar, ScienceDirect, PubMed, and SpringerLink, by using several keywords, including “medicinal plants in Guam”, “traditional uses”, “bioactive compounds”, “pharmacological properties”, and “urinary tract infections”. This review highlights the traditional uses, bioactive compounds, and pharmacological properties of five medicinal plant species, namely Euphorbia hirta, Phyllanthus amarus, Premna serratifolia, Psidium guajava, and Urena lobata. Phenolics, alkaloids, terpenoids, essential oils, and polypeptides are the leading secondary metabolites reported in different plant extracts, which have been found to have significant antimicrobial, antioxidant, anti-inflammatory, antidiabetic, and anticancer properties. The therapeutic claims made about medicinal plants in Guam are well supported by the literature, having similar applications and pharmacological properties in other regions of the world. These medicinal plants have a lot of unexplored potential that might be utilized to develop more potent drugs for the treatment of infectious diseases, as well as food and herbal supplements.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030042
Authors: Ayodeji Oluwabunmi Oriola Gugulethu Mathews Miya Moganavelli Singh Adebola Omowunmi Oyedeji
In view of the extensive use of Eugenia uniflora leaves for the management of tumours and other chronic inflammatory diseases in traditional medicine, an activity-guided fractionation of its leaf ethanolic extract led to the isolation of two flavonol glycosides. Cytotoxicity study was based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay against the non-tumourigenic human embryonic kidney (HEK-293) cells, and the cancerous liver (Hep-G2) and cervical (HeLa) cell lines. Antioxidant tests were carried out using 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and hydrogen peroxide (H2O2) radical scavenging assays, while an in vitro anti-inflammatory test was conducted using egg albumin denaturation (EAD) assay. Based on comprehensive spectroscopic and spectrometric evidence, the compounds were elucidated as myricitrin (1) and a newly described compound, 5,7-dihydroxy-3-(3,4,5-trihydroxy-6-methyltetrahydropyran-2-yloxy)-2-(2,4,5-trihydroxyphenyl)chromen-4-one, named “unifloratrin (2)”. The cytotoxicity of myricitrin (1) was comparable to 5-fluorouracil (standard drug), with a CC50 of 8.5 ± 2.2 µg/100 µL against HeLa cells. It also demonstrated better antioxidant activity, with an IC50 of 6.23 ± 1.09, 22.01 ± 2.59 and 30.46 ± 1.79 µM against DPPH, NO and H2O2 free radicals, respectively. At 20 µg/mL and an incubation time of 2 h, myricitrin was comparable to diclofenac (standard drug) in anti-inflammatory activity. This report may serve as a justification for the ethnomedicinal use of E. uniflora, while flavonol glycosides, such as myricitrin (1), could be further exploited as a candidate cytotoxic agent.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030041
Authors: Andisiwe Mnqika Adeyemi O. Aremu H. D. Janse van Rensburg Makhotso Lekhooa
In South African traditional medicine, Gomphocarpus fruticosus (L.) W.T. Aiton, Hypoxis hemerocallidea Fisch. & C.A. Mey., and Leonotis leonurus. (L.) R.Br. have been recorded among different ethnic groups to be a valuable herbal remedy for the management of depression-related conditions. The current study investigated the affinity of these three plants toward the serotonin reuptake transporter (SERT) and adenosine A1/A2 receptors. Six solvents (water, methanol, acetone, dichloromethane, petroleum ether, and hexane) were used to extract the selected plants. We established that eight extracts exerted potential affinity based on the applied in vitro binding experiment. The methanol and acetone extracts of Hypoxis hemerocallidea had 60% specific binding of [3H]citalopram, an indication that almost 40% of the plant extracts were bound to the SERT. For the adenosine receptor binding assays, methanol and hexane extracts of Leonotis leonurus were the most active, with rA1Ki values of 0.038 and 0.176 mg/mL, respectively. In addition, the dichloromethane extract of Gomphocarpus fruticosus had an rA1Ki value of 6.46 mg/mL. Extracts from the more polar solvents methanol and dichloromethane had higher binding affinity. Additionally, these plant extracts acted as antagonists at the adenosine A1 receptor. Overall, the current findings provide an indication of the potential antidepressant effects of some of the tested extracts based on their binding to the receptors evaluated. However, a combination of other in vitro assays is needed to establish possible mechanisms of action. In addition, computational analysis and profiling of plant extracts is crucial to identify the bioactive compounds with a higher affinity to the receptors. Ultimately, in vivo studies remain essential to allow for an in-depth elucidation of the mechanisms of action.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030040
Authors: Osmar Antonio Jaramillo-Morales Erik Díaz-Cervantes Lisa Dalla Via Aida Nelly Garcia-Argaez Josué Vidal Espinosa-Juárez José Carlos Ovando-Zambrano Victor Manuel Muñoz-Pérez Carmen Valadez-Vega Mirandeli Bautista
There is an urgent need for scientists to verify the pharmacological properties of medicinal plants. Leucophyllum frutescens (Lf) belongs to the family Scrophulariaceae, and it is used in the treatment of airway diseases such as cough, tuberculosis, and asthma. The methanolic extract of the aerial parts of Lf allows for the isolation and identification of verbascoside (Vb). This study aimed to evaluate the hepatoprotective effect of Vb, a caffeoyl phenylethanoid glycoside (CPG), on post-necrotic liver damage induced by thioacetamide (TA) via in vivo and in silico studies, with the latter considering a cancerous process. The aerial parts of Lf were extracted by maceration using hexane methanol (5 L/500 g/8 days). Vb was isolated from methanol extract at approximately 30%. Wistar rats were intragastrically pretreated or not with a single dose of Vb (20 mg/kg) for four days. On the fourth day, a single dose of TA (6.6 mmol/kg) was intraperitoneally injected. Blood samples and parameters related to liver damage, like AST and ALT, were obtained. Vb significantly reduced the level of liver injury following thioacetamide-induced necrosis. This was corroborated by in silico assay and docking studies, demonstrating that Vb can interact with a HeLa target through hydrogen bonds and electrostatic interactions, achieving better performance than commercial chemotherapeutic Taxol®, by 0.34 kcal/mol. AST and ALT were significantly lower in the rats pretreated with Vb. Furthermore, Vb did not induce cytotoxicity and had a median lethal dose (LD50) greater than 5000 mg/kg. These results suggest that Vb may be used as an alternative to reduce liver damage.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030039
Authors: Hudson C. Polonini Carolina C. V. Silva
An increasing number of pharmacies around the world are producing hair solutions and foams containing minoxidil for alopecia, commonly using ready-to-use vehicles such as TrichoSolTM or TrichoFoamTM. However, it is paramount to determine the chemical and microbiological compatibility of these formulations so they can be safely implemented as vehicles of choice. Also, these products usually suffer from a change of color over time, which leads to many patients prematurely discontinuing treatment. As long-term treatment is recommended, this study aimed to assess the physical–chemical and microbiological stability and investigate the color change of compounded minoxidil formulations. For that, HPLC analyses and antimicrobial effectiveness testing were conducted in a bracketed study covering concentrations from 1.0% to 7.0% of minoxidil. HPLC, pH, and metals in 5.0% minoxidil compounded products were determined using ICP-MS to evaluate the mechanisms involved in their color change. The stability of the products varied from 120 to 380 days. The color change was remarkably noticeable, but apart from this parameter, no other quality attribute was affected throughout this period, including minoxidil content, which presented only minor fluctuations. No precipitation was observed, and pH was relatively stable. It is not expected that this yellow color will impact effectiveness. Finally, we created an indicative color chart of the behavior of minoxidil in the studied vehicles.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030038
Authors: Rania Elkeeb Anomeh Avartoomian Amira S. Gouda Ahmed M. Abdel-Megied Ola Abdallah Eman Atef
The aim of the study is to evaluate the effectiveness of the pediatric sofosbuvir weight-based dosing strategy in providing an equitable drug exposure compared to the marketed dose. The physiologically based pharmacokinetic (PBPK) modeling and simulation is a valuable tool in assessing drug dosing and toxicity in populations with physiological, pathological, and genetic pharmacokinetic (PK) variability. The PBPK model of the sofosbuvir compound was developed using Simcyp® V20. The model was developed and verified using the published sofosbuvir’s physicochemical properties and clinical data from multiple studies on healthy adult volunteers, hepatitis C virus (HCV)-infected adults, and HCV-infected pediatrics. The AUC and Cmax fold ratio of (predicted/observed) fell within the acceptable range of 0.5–2 in all tested adults’ data, confirming the successful development of the sofosbuvir Simcyp® compound model. Using this model, a weight-based dosing regimen of 6 mg/kg in pediatric patients was simulated and compared to the 150 mg and 200 mg approved dose for 3–6 and 6–12 y/o pediatric patients, respectively. No dose adjustment was recommended in patients ages 6–12 y/o. However, compared to the approved 150 mg for 3–6 y/o, the weight base dose provided an equitable drug exposure to adults. Further clinical studies are warranted to verify this finding.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030037
Authors: Viktoria Milkova Kamelia Kamburova Petar Martinov Neli Vilhelmova-Ilieva Viktor Rashev
Stable multicomponent capsules for the delivery of remdesivir (Veklury®) are produced through subsequent electrostatic adsorption of oppositely charged components on oil emulsion droplets. For the first time, the encapsulation and release of the medicine Veklury® from polymer capsules was reported. In this study, the effect of the physicochemical properties of chitosan on the size and stability of the produced structures is investigated, on the loaded amount of drug and on the kinetics of drug release in conditions close to the physiological ones. Microbiological studies of the capsules and their constituents were performed via in vitro assays against HCT-8 cell lines and human coronavirus HCoV-OC43. A detailed analysis was performed on the influence of the properties of produced capsules on cytotoxicity against the chosen cell line, as well as their effect on the replication cycle of the virus, the virucidal activity of the samples against the viability of the extracellular virions, and their effect on viral adsorption on the cell membrane.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030036
Authors: Sarunya Chuanphongpanich Satapat Racha Banthita Saengsitthisak Pichai Pirakitikulr Kannika Racha
TAK1 (transforming growth factor-beta-activated kinase 1) is a crucial therapeutic target in inflammation-related diseases. This study investigated the inhibitory potential of cannflavin A, a flavonoid found in Cannabis sativa, against TAK1. Through in silico approaches, including drug-likeness analysis, ADMET assessment, molecular docking, and molecular dynamics simulation, the binding affinity and stability of cannflavin A were evaluated. The results demonstrate that cannflavin A exhibits excellent ADMET properties and displays superior binding affinity and stability at the ATP binding site of TAK1 when compared to the known inhibitor takinib. Notably, the decomposition of binding free energy unveils critical amino acid residues involved in TAK1 binding, underscoring the inhibitory effect of cannflavin A through TAK1 inhibition. These findings highlight the potential of cannflavin A as a TAK1 inhibitor and its significant implications for the development of targeted therapies in inflammation-related diseases. Through modulating inflammatory signaling pathways, cannflavin A holds promise for more effective and tailored treatment strategies, particularly in rheumatoid arthritis. This study contributes to the current understanding of cannflavin A’s application and provides a foundation for further research and innovative approaches in targeted therapies for inflammatory conditions.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030035
Authors: Volodymyr V. Oberemok Kateryna V. Laikova Kseniya A. Yurchenko Ilya A. Novikov Tatyana P. Makalish Anatolii V. Kubyshkin Oksana A. Andreeva Anastasiya I. Bilyk
The main problem in creating anti-coronavirus vaccines that target mainly proteins of the outer membrane of the virus is the rapid variability in the RNA genome of the pathogen that encodes these proteins. In addition, the introduction of technologies that can affordably and quickly produce flexible vaccine formulas that easily adapt to the emergence of new subtypes of SARS-CoV-2 is required. Universal adjuvant oligonucleotide vaccines based on conserved regions of the SARS-CoV-2 genome can take into account the dynamics of rapid changes in the virus genome, as well as be easily synthesized on automatic DNA synthesizers in large quantities in a short time. In this brief report, the effectiveness of four phosphorothioate constructs of the La-S-so-type adjuvant oligonucleotide vaccine is evaluated on B6.Cg-Tg (K18-ACE2)2 transgenic mice for the first time. In our primary trials, the oligonucleotide vaccine increased the survival rate of animals infected with SARS-CoV-2 and also reduced the destructive effects of the virus on the lung tissue of mice, activating both their innate and adaptive immunity. The obtained results show that the development of adjuvant oligonucleotide vaccine constructs of the La-S-so type is an affordable and efficient platform for the prevention of coronavirus infections, including those caused by SARS-CoV-2.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030034
Authors: Jerry O. Adeyemi
Many medicinal plants found in Africa, such as Dovyallis caffra, have been reported to contain various bioactive compounds, which have been found to reduce metal salts into their corresponding metal-based nanoparticles. In this paper, the evaluation of synthesis, characterization, and biological properties of Dovyallis caffra-mediated cassiterite (SnO2) nanoparticles was carried out. The physicochemical properties of the synthesized material were investigated using X-ray diffraction (XRD), energy dispersive X-ray analysis (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. The characterization studies revealed that the material possessed a single tetragonal cassiterite SnO2 phase, having a cluster-like foam appearance and an irregular spherical morphology with diameters ranging from 6.57 to 34.03 nm. The biological screening revealed that the prepared cassiterite (SnO2) nanoparticles exhibited cytotoxicity against the MCF-7 breast cancer cells, with an IC50 value of 62.33 µg mL−1, better than the standard drug 5-fluorouracil, with an IC50 value of 71.21 µg mL−1. The radical scavenging potential of the nanoparticles, using the DPPH assay, showed that it possessed a slightly better activity than ascorbic acid, a common antioxidant. These results suggest that the Dovyallis caffra-mediated cassiterite (SnO2) nanoparticles possess the potential to simultaneously generate and scavenge excess ROS, which in turn results in the exhibition of good cytotoxicity and antioxidant properties.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030033
Authors: Petya D. Dimitrova Tsvetozara Damyanova Tsvetelina Paunova-Krasteva
In the new antibiotic era, the exponential increase in multiresistant bacterial strains has become the main global health problem. Many researchers have focused their efforts on exploring novel or combined strategies for combating bacterial resistance. Good knowledge of the molecular mechanisms of resistance and bacterial virulence factors as key targets provides us with a good basis for resolving the problem. One particularly attractive and promising strategy is to attack the main regulatory “network” of bacterial virulence determinants known as quorum sensing (QS). The inhibition of QS signals will be a novel means of screening more effective quorum-sensing inhibitors (QSIs) and will play a key role in the use of next-generation antimicrobials in the battle against resistance. This motivated the present review to provide a comprehensive clarification of the regulatory mechanisms of quorum-sensing signaling pathways in Chromobacterium violaceum and the discovery of potential plant quorum-sensing inhibitors.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030032
Authors: Koushik Chandra Sansa Dutta Haradhan Kolya Chun-Won Kang
Cancer is a genetic disorder and its treatment usually requires a long time and expensive diagnosis. While chemotherapy is the most conventional approach in treating most cancers, patients often suffer from undesired side effects due to various pharmacokinetic aspects. To address this issue, target-oriented drug-delivery systems (DDS) or pulsatile drug-delivery systems (PDDS) have recently been developed as an alternative tool that takes care of the entire pharmacodynamic activities of drug action. Hydroxyethyl starch (HES) has emerged as an effective clinical tool for delivering anticancer agents into target cells. These systems have demonstrated significant potential as anticancer drug carrier conjugates through their innate pharmacokinetic properties with their safety profile. This review focuses primarily on the structural aspect during the use of HES or HES-based polymers as carriers for delivering well-known anticancer drugs. This review also indicates a perspective on the long-term research needed for the sake of improving modern drug-delivery systems based on HES polymers and in the form of nanocarriers.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030031
Authors: Ayhan Parlar Busra Gurel Mehmet Reşit Sönmez Meral Yüce
Alterations in the biological activity of the molecules under stress conditions have not been documented as widely in the literature yet. This study was designed to reveal the functional impacts of various oxidation conditions on a model mAb, a commercial anti-VEGF IgG molecule. The responses to antigen binding, cell proliferation, FcRn receptors, and C1q binding, which rarely appear in the current literature, were investigated. The authors report peptide mapping data, post-translational modification (PTM) analysis, cell proliferation performance, and antigen (VEGF), C1q, and FcRn binding activities of the mAb under various stress conditions. The oxidation-prone site of the mAb was determined as Met252 in the DTLMISR peptide. The VEGF binding activity and anti-cell proliferation activity of the mAbs did not alter, while C1q and FcRn binding capacity significantly decreased under oxidative stress conditions. The full report is vital for many scientific and industrial processes about mAbs. The authors recommend performing functional analyses in addition to the structural studies while investigating the impacts of stress factors on therapeutic mAbs.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030030
Authors: Chaowalit Monton Thaniya Wunnakup Jirapornchai Suksaeree Laksana Charoenchai Natawat Chankana
This study aimed to prepare tablets of black pepper extract using the Design of Experiments (DOE) approach. The levels of three factors—compressional force, croscarmellose sodium (CCS), and microcrystalline cellulose (MCC)—were screened using the one-factor-at-a-time technique, followed by the DOE utilizing the Box–Behnken design. The respective variations for each factor were as follows: compressional force (1500–2500 psi), CCS (1–3%), and MCC (32–42%). The results indicated that compressional force significantly decreased tablet thickness and friability, while increasing hardness and prolonging disintegration time. CCS significantly shortened disintegration time but did not affect tablet thickness, hardness, and friability. MCC, on the other hand, significantly increased tablet thickness and hardness, while significantly decreasing friability. Furthermore, the study observed interactions among factors and quadratic effects of each factor, which significantly influenced tablet properties. The optimal tablet formulation consisted of 2.2% CCS, 37% MCC, and a compressional force of 2000 psi. These tablets had a weight of 198.39 ± 0.49 mg, a diameter of 9.67 ± 0.01 mm, a thickness of 1.98 ± 0.02 mm, a hardness of 7.36 ± 0.24 kP, a friability of 0.11 ± 0.02%, and a disintegration time of 5.59 ± 0.39 min. The actual values obtained using the optimal conditions closely matched the predicted values, with a low percent error (less than 5%). In conclusion, the application of the DOE approach successfully developed tablets of black pepper extract, which can be utilized as food supplement products.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91030029
Authors: Lívia Bracht Jorgete Constantin Rosane Marina Peralta Adelar Bracht
The actions of Eli Lilly-rDNA glucagon and Novo Nordisk-rDNA glucagon on glycogen catabolism and related parameters were investigated using the bivascularly perfused rat liver. The technique allows glucagon to be supplied to a selective portion of the hepatic periportal region (≈39%) when the former is infused into the hepatic artery in retrograde perfusion. Both glucagon preparations were equally effective in influencing metabolism (glucose output, glycolysis and O2 uptake) when supplied to all cells along the liver sinusoids. When only a selective periportal region of the liver was supplied with the hormone, however, the action of Novo Nordisk-rDNA glucagon was proportional to the accessible cell space, whereas the action of Eli Lilly-rDNA glucagon greatly exceeded the action that was expected for the accessible space. Chromatographically, both rDNA preparations were not pure, but their impurities were not the same. The impurities in Eli Lilly-rDNA glucagon resembled those found in the similarly acting pancreatic Eli Lilly glucagon. It was concluded that the space-extrapolating action of Eli Lilly-rDNA glucagon is caused by a yet-to-be-identified impurity. The hypothesis was raised that an impurity in certain glucagon preparations can enhance cell-to-cell propagation of the glucagon signal, possibly via gap junctional communication.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020028
Authors: Volodymyr Oberemok Oksana Andreeva Edie Alieva Anastasiya Bilyk
The modern world, swaddled in the benefits of civilization, has fostered the development of science and the introduction of products of technological progress. This has allowed serious individual health problems, including those associated with viral diseases, to become targets for prophylaxis, treatment, and even cure. Human immunodeficiency viruses, hepatitis viruses, coronaviruses, and influenza viruses are among the most disturbing infectious agents in the human experience. Influenza appears to be one of the oldest viruses known to man; these viruses were among the first to cause major epidemics and pandemics in human history, collectively causing up to 0.5 million deaths worldwide each year. The main problem in the fight against influenza viruses is that they mutate constantly, which leads to molecular changes in antigens, including outer membrane glycoproteins, which play a critical role in the creation of modern vaccines. Due to the constant microevolution of the virus, influenza vaccine formulas have to be reviewed and improved every year. Today, flu vaccines represent an eternal molecular race between a person and a virus, which neither entity seems likely to win.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020027
Authors: Deepak Kulkarni Dipak Gadade Nutan Chapaitkar Santosh Shelke Sanjay Pekamwar Rushikesh Aher Ankita Ahire Manjusha Avhale Rupali Badgule Radhika Bansode Bhujang Bobade
Microneedles are gaining popularity as a new paradigm in the area of transdermal drug delivery for biomedical and healthcare applications. Efficient drug delivery with minimal invasion is the prime advantage of microneedles. The concept of the microneedle array provides an extensive surface area for efficient drug delivery. Various types of inorganics (silicon, ceramic, metal, etc.) and polymeric materials are used for the fabrication of microneedles. The polymeric microneedles have various advantages over other microneedles fabricated using inorganic material, such as biocompatibility, biodegradation, and non-toxicity. The wide variety of polymers used in microneedle fabrication can provide a broad scope for drug delivery and other biomedical applications. Multiple metallic and polymeric microneedles can be functionalized by polymer coatings for various biomedical applications. The fabrication of polymeric microneedles is shifting from conventional to advanced 3D and 4D printing technology. The multifaceted biomedical applications of polymeric microneedles include drug delivery, vaccine delivery, biosensing, and diagnostic applications. Here, we provide the overview of the current and advanced information on polymers used for fabrication, the selection criteria for polymers, biomedical applications, and the regulatory perspective of polymer-based and polymer-coated microneedles, along with a patent scenario.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020026
Authors: Sergii Demchenko Roman Lesyk Oleh Yadlovskyi Serhii Holota Sergii Yarmoluk Sergii Tsyhankov Anatolii Demchenko
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the oldest and most widely used groups of drugs nowadays. However, the problem of searching for and creating new NSAIDs remains open, primarily due to the risks owing to their short- and long-term use. In this context, triazole-azepine hybrid molecules are attractive and prospective objects for the rational design of novel potential NSAIDs. In the present work studies of 3-aryl-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepines as potential non-steroidal anti-inflammatory agents are reported. Evaluation of drug-like properties for all tested triazole-azepine hybrids was performed in silico using SwissADME. The screening of analgesic and anti-inflammatory activities was performed in vivo using acid-induced writhing and carrageenin-induced hind paw oedema models in mice. Derivatives with activity levels more potent compared with reference drugs ketorolac and diclofenac sodium were identified. Preliminary SAR was performed based on the screening results.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020025
Authors: Vesela Kokova Elisaveta Apostolova
Etifoxine is an anxiolytic drug with a dual mechanism of action. In contrast to conventional benzodiazepine anxiolytics, which induce cognitive dysfunction and myorelaxation, no memory impairment nor a decrease in motor activity is observed with etifoxine. This study aims to evaluate the effects of etifoxine on locomotor activity and passive learning in rats with diazepam-induced memory deficit. Male Wistar rats were treated intraperitoneally for 7 days with: (1) saline; (2) diazepam 2.5 mg/kg bw or (3) diazepam 2.5 mg/kg bw and etifoxine in a dose of 50 mg/kg bw. Activity cage test was used for evaluation of locomotor activity, and step-through and step-down tests were performed to study the passive learning. Etifoxine increased the number of horizontal movements on the 7th and 14th days of the experiment. The drug exhibits anti-amnesic effect in a model of diazepam-induced anterograde amnesia by enhancing long-term memory in passive learning tests. The data obtained suggest that etifoxine can reduce the benzodiazepine-induced cognitive deficit. Moreover, such a combination can alleviate the negative influence of benzodiazepines on locomotor activity. However, additional studies are necessary to translate these results into clinical practice.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020024
Authors: Kanjana Worasing Bunleu Sungthong Wiraphol Phimarn
The Zingiber montanum herbal compress remedy is a type of herbal medicine that can be used as an alternative treatment for improving pain symptoms. This study aimed to evaluate the clinical efficacy of a Z. montanum herbal compress remedy for pain relief. PubMed, Scopus, ScienceDirect, and Thai databases were systematically searched for relevant articles published from inception to December 2022. Only randomized clinical trials (RCTs) wherein the efficacy of the Z. montanum remedy was compared to that of a placebo or non-steroidal anti-inflammatory drugs (NSAIDs) were included. Six RCTs with a total of 812 patients were included in the analysis. The efficacy of the Z. montanum remedy had a significantly decreased pain score compared to the placebo (SMD = −0.63; 95% CI = −1.20, −0.06; I2 = 90%), but there was no significant difference when compared to NSAIDs (SMD = −0.61; 95% CI = −1.41, 0.81; I2 = 73%). Moreover, the efficacy of the Z. montanum remedy in terms of the flexibility score (SMD = 0.59; 95% CI −0.56, 1.74; I2 = 86.0%) and quality of life (SMD = 0.34; 95% CI −0.38, 1.05; I2 = 81.0%) was similar to that of the placebo. This meta-analysis demonstrates that the use of the Z. montanum herbal compress remedy significantly reduces the pain scores reported by patients.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020023
Authors: Venera R. Timergalieva Chiara G. M. Gennari Francesco Cilurzo Francesca Selmin Rouslan I. Moustafine
The aim of this study is to compare three different dissolution methods to assess the drug release from oral lyophilisates, based on interpolyelectrolyte complexes (IPECs). IPECs were prepared by mixing solutions of a linear polymer, Eudragit® EPO, with a polymer with a cross-linked structure, Noveon® AA-1 or Carbopol® 10 Ultrez (in ratios of 1:2 and 1:1, respectively). Metformin or metronidazole were used as model drugs to achieve a systemic or local effect. A comparative assessment of the drug release kinetics was carried out using artificial saliva and three different set-ups: a paddle stirrer (USP apparatus 2), a flow cell (USP apparatus 4) and a Franz diffusion cell. The results demonstrated that oral lyophilisates disintegrated within 1 min. In the case of metformin, the drug release was completed in about 90 min independently of the set-up. The static conditions in the Franz diffusion cell and USP apparatus 2 permitted the aggregation of the IPEC; therefore, the release profiles show a significant difference compared to the USP apparatus 4.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020022
Authors: Juliana Andriolli Ribeiro Ederlan Magri Itamar Luís Gonçalves Karina Paese Juliana Roman Alice Teresa Valduga
Yerba-mate contains in its composition a high concentration of phenolic compounds. This class of secondary metabolites exhibits strong values of molar absorptivity on ultraviolet and visible wavelengths. This study evaluated the effect of yerba-mate extracts on the in vitro solar protection factor (SPF) value of sunscreen formulations. The sunscreen formulations were prepared to have non-ionic lotion as a basis and yerba-mate extract and/or avobenzone as active agents. The SPF and resveratrol protective effect of the formulations were determined by UV-vis spectrometry. A synergic effect between the yerba-mate extract and avobenzone on the SPF was found. Yerba-mate extract at 5% improved the SPF of the avobenzone 5% formulation from 28.46 ± 5.45 to 40.48 ± 0.84. Yerba-mate extract at 5% avoided resveratrol degradation by ultraviolet radiation. At this same concentration, avobenzone produced a smaller effect than yerba-mate extracts in resveratrol protection. The formulations with yerba-mate + avobenzone presented smaller changes in pH values during 12 days of storage. The spreadability profile of yerba-mate and avobenzone formulations was similar to the profile of avobenzone formulations. The results reported here show the suitability of the yerba-mate extract use in photoprotective formulations, highlighting their in vitro effect and opening possibilities for new investigations exploring this property.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020021
Authors: Kateryna Typlynska Yuliya Kondratova Liliya Logoyda
Our main target was to develop methods for the quality control of the tablet «ramipril» according to the indicators of «Quantitative determination», «Impurities» and «Dissolution». New, precise, accurate and green HPLC methods were developed for the determination of ramipril and its impurities in tablets. The separation was accomplished using a diode array detector at 210 nm with an isocratic and gradient mobile phase consisting of a 0.2 g/L solution of sodium hexanesulfonate (pH 2.7) and the acetonitrile and chromatographic columns Acclaim 120 C18 and Inertsil ODS-3. The developed method was validated in accordance with ICH guidelines. The analysis of impurities was performed within a run duration of less than 25 min, which is about a two times shorter than that of the official Ph. Eur. method. The analysis of ramipril in tablets was performed with a run duration of less than 4.5 min, which is about three times shorter than that of the official USP method. The developed methods were successfully applied for the quality control of the tablet «ramipril» according to the indicators of «Quantitative determination», «Impurities» and «Dissolution». In addition, they proved its superiority over the reported methods in terms of greenness using different assessment tools.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020020
Authors: Juan Luis Pérez-Salas Martha Rocío Moreno-Jiménez Nuria Elizabeth Rocha-Guzmán Rubén Francisco González-Laredo Luis Medina-Torres José Alberto Gallegos-Infante
Skin inflammation occurs as an immune response to various stimuli such as ultraviolet light, irritants, or any type of skin barrier injury. Finding safe and effective drugs to combat skin inflammation remains a research challenge. Ethical and legal considerations in animal testing encourage the development of in vitro and ex vivo models for the detection of skin inflammation. This report presents an updated review of non-animal study models available for screening drugs with anti-inflammatory potential. It includes a description of the basic methods used to inhibit protein denaturation and red blood cell membrane stability. Three in vitro inhibition assay methods for enzymes relevant to the skin inflammatory process are then described. The development of cell culture models is described: relatively simple and easy-to-produce two-dimensional (2D) skin cell cultures that allow assessment of response to a given stimulus, three-dimensional (3D) cell cultures that better mimic human skin physiology by more accurately replicating mechanical and chemical signals, and vascularized 3D skin models with dynamic perfusion and microfluidic devices known as skin on a chip. Finally, ex vivo skin models are presented that could more accurately represent human skin in terms of structure, cell signaling mechanisms, and absorption effects. Although the current development of models without the use of animals is promising, improvements and refinements are needed to make the models more suitable as screening platforms for topical anti-inflammatory drugs.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020019
Authors: María Taboada-Alquerque Danilo Pajaro-Valenzuela Karina Caballero-Gallardo Alejandro Cifuentes Elena Ibáñez Maicol Ahumedo-Monterrosa Elena E. Stashenko Jesus Olivero-Verbel
Carnosol is a natural diterpene present in Rosmarinus officinalis L. (rosemary) with anti-tumor and anti-inflammatory properties. Despite its importance, the pharmacological mechanisms underlying the interactions between carnosol and human targets are still unclear. The goal was to identify plausible human target for carnosol and the network pharmacology. Rosemary was analyzed using HPLC-QTOF-MS/MS. Potential carnosol targets were identified using docking and a public database (CTD). Carnosol was screened against 708 human proteins using AutoDock Vina, and affinity values were used as prioritization criteria. The targets set was uploaded to WebGestalt to obtain Gene Ontology (GO) and KEGG pathway enrichment analysis. HPLC-QTOF-MS/MS analyses allowed the tentative annotation of nine chemicals, with carnosol being the most ionized. There were 53 plausible targets for carnosol, with 20 identified using virtual screening, including Hsp90α (−10.9 kcal/mol), AKR1C3 (−10.4 kcal/mol), and Hsp90β (−10.4 kcal/mol), and 33 identified from CTD. The potential targets for carnosol identified with PPI and molecular docking were HSP90AA1, MAPK1, MAPK3, CAT, JUN, AHR, and CASP3. GO terms and KEGG pathways analysis found that carnosol is closely related to infection (Chagas, influenza A, toxoplasmosis, and pertussis) and inflammation (IL-17 and TNF signaling pathway and Th-17 cell differentiation). These results demonstrated that carnosol may induce an immuno-inflammatory response.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020018
Authors: Mohamed F. Zayed
Cancer is a large group of diseases that can affect any organ or body tissue due to the abnormal cellular growth with the unknown reasons. Many of the existing chemotherapeutic agents are highly toxic with a low level of selectivity. Additionally, they lead to development of therapeutic resistance. Hence, the development of targeted chemotherapeutic agents with low side effects and high selectivity is required for cancer treatment. Quinazoline is a vital scaffold well-known to be linked with several biological activities. The anticancer activity is one of the prominent biological activities of this scaffold. Several established anticancer quinazolines work by different mechanisms on the various molecular targets. The aim of this review is to present different features of medicinal chemistry as drug design, structure activity relationship, and mode of action of some targeted anticancer quinazoline derivatives. It gives comprehensive attention on the chemotherapeutic activity of quinazolines in the viewpoint of drug discovery and its development. This review provides panoramic view to the medicinal chemists for supporting their efforts to design and synthesize novel quinazolines as targeted chemotherapeutic agents.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91020017
Authors: Chaowalit Monton Piyapa Keawchay Chantisa Pokkrong Pariyakorn Kamnoedthapaya Abhiruj Navabhatra Jirapornchai Suksaeree Thaniya Wunnakup Natawat Chankana Thanapat Songsak
This research sought to optimize the microwave-assisted extraction of Chatuphalathika as an herbal recipe maximizing the active compounds and the antioxidant activity by the Box–Behnken design. Three factors—microwave power, time, and cycle—were varied. Eight responses—extraction yield, total phenolic content, gallic acid content, corilagin content, chebulagic acid, chebulinic acid, IC50 from DPPH assay, and IC50 from FRAP assay—were monitored. Furthermore, cytotoxicity was evaluated to ensure the safety of the extract. After that, the optimized extract was compressed into tablets. The results showed that the optimal condition of the microwave-assisted extraction gave the simultaneous maximum extraction yield, total phenolic content, and antioxidant activity with a microwave power of 450 W for 30 s and 3 cycles. The extract obtained from the optimal condition exhibited a good safety profile although a concentration of 5 mg/mL was used. The optimized tablets were achieved when a compression force of 1500 psi and magnesium stearate of 1% were applied, and no sodium starch glycolate was added. In conclusion, the optimal green extraction method could be used for the extraction of the Chatuphalathika. Furthermore, the fabrication of Chatuphalathika tablets was successful, as the tablets had low friability with a short disintegration time.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010016
Authors: Tamam El-Elimat Haya S. El-Qaderi Wael M. Hananeh Mahmoud M. Abu AlSamen Ahmed H. Al Sharie Musa A. Alshehabat Mohammad Al-Gharaibeh Feras Q. Alali
The wound healing potential of the aerial parts of Hypericum triquetrifolium Turra (Hypericaceae) was evaluated using an in vivo excision wound model in rats. Adult male Sprague Dawley rats were randomly assigned into seven groups; blank vehicles (olive oil and petroleum jelly), negative control, treatments [H. triquetrifolium ethanolic extract in petroleum jelly (5% and 10%) and H. triquetrifolium olive oil macerate (100 and 200 g/L)], and positive control (MEBO). Treatments were applied topically once daily until the wounds had completely healed. Wound areas and contraction rates were calculated, and full-thickness samples of the healed skin were collected for histopathological examination. H. triquetrifolium ointment (5%) showed the best wound healing activity with statistically significant differences when compared with the MEBO, petroleum jelly, and the negative control groups. Tissue sections were histopathologically examined in terms of re-epithelialization, granulation tissue development, collagen deposition, inflammatory cell infiltration, angiogenesis, and ulcer formation to support the in vivo excision wound model findings. H. triquetrifolium ointment (5%) showed the best histopathological scores in both re-epithelialization and ulcer formation. For quality control purposes, a high-performance liquid chromatography (HPLC) method was used to quantify key marker compounds in the extract, namely hypericin and rutin which showed a content of 0.64% and 4.46% (w/w), respectively. Based on the experimental results, H. triquetrifolium ointment (5%) exhibits remarkable wound healing properties at various stages of the wound healing process. Further investigations to prove its safety and efficacy in different types of wounds and to uncover its cellular mechanisms are warranted.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010015
Authors: Muhammad Iqhrammullah Diva Rayyan Rizki Agnia Purnama Teuku Fais Duta Harapan Harapan Rinaldi Idroes Binawati Ginting
Essential oils are potential therapeutics for coronavirus disease 2019 (COVID-19), in which some of the volatile compounds of essential oils have been well known for their broad antiviral activities. These therapeutic candidates have been shown to regulate the excessive secretion of pro-inflammatory cytokines, which underlies the pathogenesis of severe COVID-19. We aimed to identify molecular targets of essential oils in disrupting the cell entry and replication of SARS-CoV-2, hence being active as antivirals. Literature searches were performed on PubMed, Scopus, Scillit, and CaPlus/SciFinder (7 December 2022) with a truncated title implying the anti-SARS-CoV-2 activity of essential oil. Data were collected from the eligible studies and described narratively. Quality appraisal was performed on the included studies. A total of eight studies were included in this review; four of which used enzyme inhibition assay, one—pseudo-SARS-CoV-2 culture; two—whole SARS-CoV-2 culture; and one—ACE2-expressing cancer cells. Essential oils may prevent the SARS-CoV-2 infection by targeting its receptors on the cells (ACE2 and TMPRSS2). Menthol, 1,8-cineole, and camphor are among the volatile compounds which serve as potential ACE2 blockers. β-caryophyllene may selectively target the SARS-CoV-2 spike protein and inhibit viral entry. Other interactions with SARS-CoV-2 proteases and RdRp are observed based on molecular docking. In conclusion, essential oils could target proteins related to the SARS-CoV-2 entry and replication. Further studies with improved and uniform study designs should be carried out to optimize essential oils as COVID-19 therapies.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010014
Authors: So-Yeon Kim Minji Hong Ponnuvel Deepa Kandhasamy Sowndhararajan Se Jin Park SeonJu Park Songmun Kim
This study aimed to elucidate the anti-inflammatory activity of C. tinctorius leaves by measuring inflammatory parameters such as nitric oxide (NO) production and mRNA expression of iNOS, interleukin-6 (IL-6), and IL-1β in lipopolysaccharide (LPS)-induced HaCaT cells. Further, the effect of C. tinctorius ethanol extract on the MAPKs/NF-κB signaling pathway was examined in HaCaT cells. The phytochemical profile of the ethanol extract of C. tinctorius leaves was determined using UPLC-QTOF-MS/MS. The results indicated that the ethanol extract of C. tinctorius effectively attenuated LPS-induced secretion of NO, IL-6, and IL-1β in HaCaT cells. Further, LPS-stimulated mRNA and protein expressions of iNOS were decreased by pre-treatment with C. tinctorius ethanol extract at the transcriptional level in HaCaT cells. Moreover, the ethanol extract of C. tinctorius suppressed NF-κB signaling in LPS-induced HaCaT cells. This suppression was mediated by MAPKs/NF-κB signaling, inhibiting the phosphorylation of p38 and p65 in HaCaT cells. However, there is no significant effect on the phosphorylation of JNK by the ethanol extract. The QTOF-MS/MS analysis revealed the identification of 27 components in the ethanol extract of C. tinctorius leaves. The data demonstrate that the ethanol extract of C. tinctorius leaves protects the LPS-induced HaCaT cells by inhibiting the expression of iNOS, IL-6, and IL-1β and suppressing the phosphorylation of the p38, p65, p-JNK via inactivation of MAPKs/NF-κB signaling pathway. These results demonstrate that C. tinctorius leaves may serve as a potential candidate to prevent inflammation-related diseases.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010013
Authors: Yulian Konechnyi Andrii Lozynskyi Iryna Ivasechko Tetiana Dumych Solomiya Paryzhak Oksana Hrushka Ulyana Partyka Iryna Pasichnyuk Dmytro Khylyuk Roman Lesyk
Searching for new types of biological activities among preliminarily identified hit compounds is a key challenge in modern medicinal chemistry. In our study, a previously studied 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl]-propionic acid (Les-6614) was screened for antimicrobial, antifungal, anti-allergic, and antitumor activities. Moreover, cytotoxicity, molecular docking, and SwissAdme online target screening were accomplished. It was determined that the Les-6614 has slight antimicrobial and antitumor activity. However, the studied compound decreased IgE levels in sensitized guinea pigs by 33–86% and reduced IgA, IgM, IL-2, and TNF-α, indicating anti-inflammatory and anti-allergic aactivities. According to the SwissADME web tool, target predictions for Les-6614 potentially have an affinity for lysosomal protective protein, Thromboxane-A synthase, and PPARγ. The molecular docking confirmed that the studied 2-thioxo-4-thiazolidinone derivative showed good bonding with LLP and TXAS, leading to stable protein–ligand complexes. Additionally, Les-6614 is a potential PPARγ modulator, which is important in the pathogenesis of allergy, cancer, and cardiovascular diseases.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010012
Authors: Ali M. Alaseem Khalid Alhazzani Ahmed Zuwaiel Alanazi Yasser Alqarni Mohammad M. Algahtani Abdullah S. Alhamed Glowi Alasiri Fahad T. Alotaibi Talha Jawaid Jehad A. Aldali
Background: Combining antiangiogenic drugs with other chemotherapeutic drugs has been found to produce superior therapeutic outcomes and prevent drug resistance in a variety of cancers. Methods: Experimental assays such as the MTT assay, flow cytometry, western blotting, and qPCR have been used to evaluate the efficacy of combination therapy. Results: When compared to controls and monotherapies, the combination treatment of axitinib and idasanutlin demonstrated a substantial decrease in cell viability at lower doses, a significant decrease in migration, and a shift toward early and late apoptosis. This study examined major apoptotic, metastatic, and angiogenic factors, including MDM2, p21, BCL-2, BCL-XL, and MMP9, which have showed differential expressions at the protein and mRNA levels after combination. Axitinib and idasanutlin decreased tumorigenesis and migration in vitro in the MCF-7 cell line when compared to other chemotherapeutic medications. The suggested mechanisms of the antitumorigenic effect of the combination therapy may depend on its capacity to promote the production of apoptotic markers and reduce antiapoptotic markers. Conclusions: Treatments with axitinib and idasanutlin demonstrated effective therapeutic targeting of the primary angiogenic growth factor and, consequently, the pro-metastatic arbitrators. This will not only eliminate cancer cells but also stop other malignant processes and ultimately reduce the metastatic cascade.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010011
Authors: Laddawan Lalert Nutnicha Tantarungsee Tipthanan Chotipinit Wilawan Ji-au Anan Srikiatkhachorn Supang Maneesri-le Grand
Paracetamol (acetaminophen, APAP) is known as a safe pain reliever; however, its negative effects on the central nervous system have gradually been reported. We examined alterations in learning and memory, and brain-derived neurotrophic factor (BDNF) expression in the frontal cortex and hippocampus at different durations of APAP treatment in rats. Novel object recognition (NOR) and Morris water maze (MWM) paradigms were used to assess learning and memory in rats fed with 200 mg/kg APAP at single-dose, 15-day or 30-day treatments. BDNF expression was evaluated through immunohistochemistry and Western blotting. The single-dose APAP treatment did not alter the NOR performance. However, deficits in the NOR and MWM capacities were detected in the rats with longer durations of APAP treatment. An analysis of BDNF expression revealed no significant change in BDNF expression in the single-dose APAP treatment, while rats given APAP for extended periods as treatment showed a significant decrement in this protein in the frontal cortex and hippocampus. Short-term APAP treatment has no effect on learning and memory, or BDNF expression; however, long-term APAP exposure causes cognitive impairment. The diminishment of the BDNF level in the frontal cortex and hippocampus due to the long period of treatment with APAP may at least in part be involved in altered learning and memory in rats.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010010
Authors: Filip Bielec Małgorzata Brauncajs Dorota Pastuszak-Lewandoska
Funding is often a constraint when planning research, especially in countries where basic research is underfunded. Researchers must take into account these limitations, e.g., in relation to the selection of appropriate reagents, the source of which may affect the study’s final results. The aim of this article was to compare the results of bacteria susceptibility testing using three different sources of antimicrobial: the pure powder available from the supplier and two tablet formulations with different excipients. The chosen substance was furazidin (nitrofuran derivative). The susceptibility was tested on a group of 45 uropathogenic Enterobacterales using both microdilution and disk diffusion methods. The obtained results indicated that despite the relatively higher price, the powder appeared to be the best substance for scientific purposes, especially for quantitative determinations.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010009
Authors: Noor Akbar Naveed Ahmed Khan Taleb Ibrahim Mustafa Khamis Amir Sada Khan Ahmad M. Alharbi Hasan Alfahemi Ruqaiyyah Siddiqui
Herein, we utilized several deep eutectic solvents (DES) that were based on hydrogen donors and hydrogen acceptors for their antibacterial application. These DES were tested for their bactericidal activities against Gram-positive (Streptococcus pyogenes, Bacillus cereus, Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli K1, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens) bacteria. Using lactate dehydrogenase assays, DES were evaluated for their cytopathic effects towards human cells. Results from antibacterial tests revealed that DES prepared from the combination of methyl-trioctylammonium chloride and glycerol (DES-4) and DES prepared form methyl-trioctylammonium chloride and fructose (DES-11) at a 2 µL dose showed broad-spectrum antibacterial behavior and had the highest bactericidal activity. Moreover, DES-4 showed 40% and 68% antibacterial activity against P. aeruginosa and E. coli K1, respectively. Similarly, DES-11 eliminated 65% and 61% E. coli K1 and P. aeruginosa, respectively. Among Gram-positive bacteria, DES-4 showed important antibacterial activity, inhibiting 75% of B. cereus and 51% of S. pneumoniae. Likewise, DES-11 depicted 70% B. cereus and 50% S. pneumoniae bactericidal effects. Finally, the DES showed limited cytotoxic properties against human cell lines with the exception of the DES prepared from Methyltrioctylammonium chloride and Citric acid (DES-10), which had 88% cytotoxic effects. These findings suggest that DES depict potent antibacterial efficacies and cause minimal damage to human cells. It can be concluded that the selected DES in this study could be utilized as valuable and novel antibacterial drugs against bacterial infections. In future work, the mechanisms for bactericides and the cytotoxicity effects of these DES will be investigated.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010008
Authors: Scientia Pharmaceutica Editorial Office Scientia Pharmaceutica Editorial Office
High-quality academic publishing is built on rigorous peer review [...]
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010007
Authors: Atef A. El-Hela Marwa S. Abu Bakr Mostafa M. Hegazy Mohammed A. Dahab Ayman Abo Elmaaty Adel Ehab Ibrahim Sami El Deeb Hatem S. Abbass
Virtual screening of the potential lead chemotherapeutic phytochemicals from medicinal plants has useful application in the field of in-silico modelling and computer-based drug design by orienting and scoring ligands in the active binding site of a target protein. The phytochemical investigation of the Pterocephalus frutescens extract in n-butanol resulted in the isolation and structure elucidation of three iridoids and four flavonoids which were identified as Geniposide (1), Geniposidic acid (2), Nepetanudoside C (3), Isovitexin (4), Luteolin-7-O-glucoside (5) Isoorientin (6) and Orientin (7), respectively. Molecular docking studies were used to compare the binding energies of the isolated phytochemicals at four biological cancer-relevant targets; namely, aromatase, carbonic anhydrase IX, fatty acid synthase, and topoisomerase II-DNA complex. The docking study concluded that the isolated compounds have promising cytotoxic activities, in particular, Luteolin-7-O-glucoside (5) and Orientin (7) which exhibited high binding affinities among the isolated compounds at the active sites of the target enzymes; Aromatase (−8.73 Kcal/mol), and Carbonic anhydrase IX (−8.92 Kcal/mol), respectively, surpassing the corresponding binding scores of the co-crystallized ligands and the reference drugs at these target enzymes. Additionally, among the isolated compounds, Luteolin-7-O-glucoside (5) showed the most outstanding binding affinities at the active sites of the target enzymes; Fatty acid synthase, and Topisomerase II-DNA complex with binding scores of −6.82, and −7.99 Kcal/mol, respectively. Finally, the SwissADME online web tool predicted that most of these compounds possessed acceptable oral bioavailability and drug likeness characteristics.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010006
Authors: Hee Yeon Kim Ki Yeon Lee Minju Kim Minji Hong Ponnuvel Deepa Songmun Kim
In the food and beverage industries, replacing synthetic colorants with plant-based colorants has become popular in recent times. Purple corn (Zea mays L.) is an important source of natural colorants due to its range in color from orange to purple. The whole plant of purple corn has a high amount of anthocyanin content. Anthocyanin is the water-soluble pigment found in various fruits and vegetables. The color pigments are chiefly found in the pericarp or kernels, in addition to corn cobs. Purple corn is rich in various health-promoting compounds, mainly anthocyanins such as cyanidin-3-O-glucoside, perlagonidin-3-O-glucoside, peonidin 3-O-glucoside, and their malonylated forms. This review emphasized recent updates regarding the in vitro and in vivo biological properties of extracts and compounds from purple corn. Purple corn color extracts possess a variety of biological properties, including antioxidant, anti-inflammatory, anticancer, anti-diabetic, anti-obesity, etc. The results of in vitro and in vivo studies of the biological properties of purple corn could lead to the development of different health-promoting products in the near future.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010005
Authors: Yuliia Kremin Lilia Lesyk Roman Lesyk Oksana Levytska Bohdan Hromovyk
As members of a public trust profession, pharmacists are the most accessible medical team members. Therefore, every pharmacist must know the scope of their professional roles (PR) and professional functions (PF). The study aimed to detail the major PR into a pooled set of PF. The research materials were the provisions of the World Health Organization, the International Pharmaceutical Federation, and scientific works on the PR of pharmacists. Methods of critical analysis, concretization, functional decomposition, and scientific generalization were used. As a result of detailing the 10 main PR according to the “ten-star pharmacist” concept for each, a combined set of partial PFs of the pharmacist was obtained. The decomposition takes into account the principle of complexity limitation, which allowed three to six partial PF for the respective PR to be obtained, namely: three PFs for a life-long-learner, five PFs for a caregiver, a decision-maker, a teacher, a leader, a researcher, an entrepreneur, and an agent of positive change, six PFs for a communicator and a manager. Thus, due to the decomposition of each of the 10 main PR of the pharmacist into three or six corresponding partial PFs, we received a multifunctional verbal model of difficult to organize, professional activities, which is identified by a total of 50 PFs. The importance of using this model in formulating professional competencies and learning outcomes of educational programs for pharmacists is emphasized.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010004
Authors: Julia Maria Borowiecka Bartosz Dalewski Łukasz Pałka
Platelet-rich plasma (PRP) has become an increasingly popular alternative or additional method in treating androgenic alopecia (AGA). AGA is a multifactorial disease, in which testosterone plays a significant role in influencing hair growth. The aim of this study was to evaluate the effectiveness of PRP treatment in AGA affecting men and women. The research was performed using the following databases: PubMed, Embase, and Cochrane Library. The effects were measured with a TrichoScan by comparing the initial and final hair density. A significant difference was observed between the areas of the scalp where PRP injections were made and those where saline was administered. Compared to conventional minoxidil 5% topical PRP, PRP is more effective in treating alopecia. A beneficial outcome of combined therapy with PRP and minoxidil 5% was observed. Therefore, PRP is not only an excellent alternative for patients in whom the minoxidil 5% topical monotherapy did not bring the expected effects or who experienced unacceptable side effects, but can also be used as a complementary therapy.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010003
Authors: Laita Nurjannah Azmi Azhari Unang Supratman
Zingiberaceae is commonly known as the ginger family and has been extensively studied in the last decades for its pharmacological purposes. The study of ginger includes microorganisms known as endophytes, which raise interest for the research community because they can produce a wide range of secondary metabolites. This review discusses the secondary metabolites of endophytes from the Zingiberaceae family and their pharmacological activities. We detail the group of secondary metabolites, updated for its absolute structures, source and part origins, and, especially, pharmacological divided properties. Zingiberaceae endophytes have 106 volatile compounds and 52 isolated constituents, including 17 polyketides, five nonribosomal peptides, five aromatic compounds, three alkaloids, and 21 terpene-alkaloids. They have antimicrobial, anticancer, antioxidant, and anti-inflammatory activities. Secondary metabolites from plant endophytes of the Zingiberaceae family have the potential to be therapeutic drugs in the future. Research on endophytic bacteria or fungi has been little performed. Therefore, this study supports a new drug discovery from Zingiberaceae endophytes and compares them for future drug development.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010002
Authors: Dela Rosa Berna Elya Muhammad Hanafi Alfi Khatib Muhammad Imam Surya
Artabotrys sumatranus is one of the Artabotrys species, which lives in Sumatera, Java, and Borneo in Indonesia. No research has been found related to its activity. The objective of this study was to explore the potential of A. sumatranus leaf and twig extracts as the source of an anti-diabetic agent through the α-glucosidase inhibition mechanism, as well as the relationship between the antioxidant and the α-glucosidase inhibition activities in these extracts. Ethanol extracts from leaf and twig A. sumatranus were subjected to several assays: total phenolic content, total flavonoid content, antioxidant activity using DPPH (2,2-diphenyl-1-picrylhydrazyl), radical scavenging activity, and FRAP (ferric reducing antioxidant power) analysis, as well as α-glucosidase inhibition. Later, GC-MS (gas chromatography-mass spectrometer) and LC-MS/MS (liquid chromatography-mass spectrometer/mass spectrometer) analysis were conducted to identify the compounds inside the extracts. The identified compounds were tested for potential α-glucosidase inhibition activity using a molecular docking simulation. As a result, the A. sumatranus leaf extract showed more potential than the twig extract as α-glucosidase inhibitor and antioxidant agent. In addition, from the comparison between the measured quantities, it can be deduced that most of the α-glucosidase active compounds in the A. sumatranus are also antioxidant agents. Several active compounds with a high affinity to α-glucosidase inhibition were identified using the molecular docking simulation. It was concluded that A. sumatranus twig and leaf extracts seem to be potential sources of α-glucosidase inhibitors.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm91010001
Authors: Menna M. Abdellatif Sara Mohamed Ahmed Mohamed A. El-Nabarawi Mahmoud Teaima
To explore the performance of the cationic nanocarrier leciplex (LPX) in escalating the oral bioavailability of vancomycin hydrochloride (VAN) by promoting its intestinal permeability. With the aid of a D-optimal design, the effect of numerous factors, including lipid molar ratio, cationic surfactant molar ratio, cationic surfactant type, and lipid type, on LPX characteristics, including entrapment efficacy (EE%), particle size (P.S.), polydispersity index (P.I.), zeta potential value (Z.P.), and steady-state flux (Jss) were assessed. The optimized formula was further evaluated in terms of morphology, ex vivo permeation, stability, cytotoxicity, and in vivo pharmacokinetic study. The optimized formula was spherical-shaped with an E.E. of 85.2 ± 0.95%, a P.S. of 52.74 ± 0.91 nm, a P.I. of 0.21 ± 0.02, a Z.P. of + 60.8 ± 1.75 mV, and a Jss of 175.03 ± 1.68 µg/cm2/h. Furthermore, the formula increased the intestinal permeability of VAN by 2.3-fold compared to the drug solution. Additionally, the formula was stable, revealed good mucoadhesive properties, and was well tolerated for oral administration. The in vivo pharmacokinetic study demonstrated that the VAN Cmax increased by 2.99-folds and AUC0-12 by 3.41-folds compared to the drug solution. These outcomes proved the potentiality of LPX in increasing the oral bioavailability of poorly absorbed drugs.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040073
Authors: José Alberto Gallegos-Infante María del Pilar Galindo-Galindo Martha Rocío Moreno-Jiménez Nuria Elizabeth Rocha-Guzmán Rubén Francisco González-Laredo
Quercus resinosa leaves are rich in polyphenol compounds, however, they are unstable to several chemical and physical factors that limit their activity. Several methods have been developed to solve such problems, among which bigels can be mentioned and obtained using hydrogels and oleogels. The mechanical characterization of this type of materials is by using rheological methods. Although the use of these methods is well documented, the Carreau-Yasuda model has been little used to evaluate the effect of polyphenols on the mechanical behavior of bigels. Therefore, bigels were obtained from hydrogels (guar gum/xanthan gum, 0.5/0.5% w/v) and oleogels (sesame oil/sorbitan monostearate 10% w/w). Micrographs, linear viscoelasticity range, frequency sweep, and single shear tests were performed. The data were analyzed using ANOVA and Tukey test (p < 0.05); micrographs showed linear relationship between polyphenols concentration and droplet size. Liquid fraction of bigels showed a pseudoplastic behavior, while the parameters of Carreau-Yasuda model showed that the highest value of the complex viscosity at zero shear was at the lowest concentration of extract; the relaxation time presented the lowest value at higher concentrations of extracts. These results indicate that the presence of polyphenols modifyes the mechanical behavior of bigels.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040072
Authors: Mohammed A. Albarki Maureen D. Donovan
Nanoparticles provide promising advantages in advanced delivery systems for enhanced drug delivery and targeting. The use of a biodegradable polymer such as PLGA (poly lactic-co-glycolic acid) promotes improved nanoparticle safety and, to some extent, provides the ability to modify nanoparticle surface properties. This study compared the effect of altering the surface charge on the translocation of PLGA nanoparticles across excised nasal mucosal tissues. Nanoparticles (average diameter of 60–100 nm) loaded with Nile Red (lipophilic fluorescent dye) were fabricated using a nanoprecipitation method. The effects of nanoparticle surface charge were investigated by comparing the transfer of untreated nanoparticles (negatively charged) and positively charged PLGA nanoparticles, which were modified using PAMAM dendrimer (polyamidoamine, 5th generation). All nanoparticles were able to be transferred in measurable quantities into both nasal respiratory and olfactory mucosae within 30 min. The total nanoparticle uptake was less than 5% of the nanoparticle mass exposed to the tissue surface. The cationic nanoparticles showed a significantly lower transfer into the mucosal tissues where the amount of nanoparticles transferred was 1.8–4-fold lower compared to the untreated negatively charged nanoparticles. The modification of the nanoparticle surface charge can alter the nanoparticle interaction with the nasal epithelial surface, which can result in decreasing the nanoparticle transfer into the nasal mucosa.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040071
Authors: Reem A. Aldeeb Mohamed Farid El-Miligi Mohamed El-Nabarawi Randa Tag Hany M. S. Amin A. A. Taha
Telmisartan (Tel) is a potent antihypertensive drug with a very poor aqueous solubility, especially in pH ranging from 3 to 9 (i.e., biological fluids) that results in poor bioavailability. Our aim was to improve Tel solubility and dissolution rates without the need for expensive multistep procedures, and without inclusion of alkalinizers. This study adopted the use of surface solid dispersions (SSDs) employing superdisintegrants, hydrophilic polymers and combined carriers including a superdisintegrant with a hydrophilic polymer. Tel-SSDs were formulated using thesolvent evaporation method. Compatibility between Tel and different carriers was examined via FT-IR. Tel-SSDs were evaluated optically and thermally to reveal a complete loss of the crystalline nature of the drug. Both drug content and percentage yield were calculated to judge the efficiency of the preparation technique used. Saturation, aqueous solubility, and dissolutions rates were determined. Dissolution profiles were studied using model dependent and independent approaches and were subjected to the pair-wise procedure using the DDsolver software program. Effect of aging was studied by comparing the drug content and dissolution profiles of freshly prepared SSDs with aged samples. All Tel-SSDs showed acceptable physical properties. Tel-SSDs showed pertinent enhancement related to the carrier used. Combined surface solid dispersions employing superdisintegrant croscarmellose sodium with either hydrophilic polymer PEG 4000 or Poloxamer 407 gave remarkable enhancement in solubility and dissolution rates of Tel where more than 90% of the drug was released within 20 min. The effect of aging results proved a non-significant difference in the drug content and dissolution profiles between fresh and aged samples. Formulation of Tel SSDs using combined carriers proved to be effective in enhancing the aqueous solubility and dissolution rates of Tel, as well as showing good stability upon aging.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040070
Authors: Erick Sierra-Campos Mónica A. Valdez-Solana Estela Ruiz-Baca Erica K. Ventura-García Claudia I. Avitia-Domínguez Miguel Aguilera-Ortiz Alfredo Téllez-Valencia
Most human fungal infections exhibit significant defensive oxidative stress responses, which contribute to their pathogenicity. An important component of these reactions is the activation of catalase for detoxification. To discover new antifungal chemicals, the antifungal activity of methanol extracts of Moringa oleifera from two commercial products (Akuanandi and Mas Lait) was investigated. The methanolic extracts’ activity against Sporothrix schenckii was determined using an assay for minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC). The MIC concentrations varied between 0.5 μg/mL and 8 μg/mL. Akuanandi extract had the lowest MIC (0.5 μg/mL) and MLC (1 μg/mL) values. M. oleifera methanolic extracts were tested for catalase inhibition. The Ki values of the M. oleifera extract against S. schenckii catalase (SsCAT) was found to be 0.7 μg/mL for MOE-AK and 0.08 μg/mL for MOE-ML. Catalase’s 3D structure in SsCAT is unknown. The homology of SsCAT was modeled with an in silico study using a 3D structure from SWISS MODEL and validation the predicted 3D structure was carried out using PROCHECK and MolProbity. Docking simulations were used to analyze protein interactions using Pymol, PoseView, and PLIP. The results revealed that M. oleifera glucosinolates interacts with SsCAT. A molecular interaction analysis revealed two inhibitor compounds (glucosinalbin and glucomoringin) with high binding affinity to key allosteric-site residues. The binding energies revealed that glucosinalbin and glucomoringin bind with high affinity to SsCAT (docking energy values: −9.8 and −9.0 kcal/mol, respectively). The findings of this study suggest that glucosinolates derived from M. oleifera could be used instead of synthetic fungicides to control S. schenckii infections. We hope that the findings of this work will be valuable for developing and testing novel natural anti-sporothrix therapeutic agents in the future.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040069
Authors: Ulayatul Kustiati Suleyman Ergün Srikanth Karnati Dwi Aris Agung Nugrahaningsih Dwi Liliek Kusindarta Hevi Wihadmadyatami
Adenocarcinoma lung cancer is a type of non-small cell lung carcinoma (NSCLC), which accounts for 85% of lung cancer incidence globally. The therapies that are being applied, both conventional therapies and antibody-based treatments, are still found to have side effects. Several previous studies have demonstrated the ability of the ethanolic extract of Ocimum sanctum Linn. (EEOS) as an ethnomedicine with anti-tumor properties. The aim of this study was to determine the effect of Ocimum sanctum Linn. ethanolic extract in inhibiting the proliferation, angiogenesis, and migration of A549 cells (NSCLC). The adhesion as well as the migration assay was performed. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of αvβ3 integrins, α5β1 integrins, and VEGF. The cells were divided into the following treatment groups: control (non-treated/NT), positive control (AP3/inhibitor β3 80 µg/mL), cisplatin (9 µg/mL), and EEOS at concentrations of 50, 70, 100, and 200 µg/mL. The results showed that EEOS inhibits the adhesion ability and migration of A549 cells, with an optimal concentration of 200 µg/mL. ELISA testing showed that the group of A549 cells given EEOS 200 µg/mL presented a decrease in the optimal expression of integrin α5β1, integrin αvβ3, and VEGF.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040068
Authors: Tanpong Chaiwarit Niphattha Aodsab Pimonnart Promyos Pattaraporn Panraksa Suruk Udomsom Pensak Jantrawut
Depression is a mental illness causing a continuous negative feeling and loss of interest and affects physical and mental health. Mirtazapine (MTZ) is an effective medicine for treating depression, but patients lack compliance. However, transforming a pharmaceutical dosage form to an orodispersible film (ODF) could resolve this issue. This study aims to fabricate ODF-loading mirtazapine, using a syringe extrusion 3D printer, and compare its properties with the solvent-casting method. The ODFs were prepared by dissolving the mirtazapine in a hydroxypropyl methylcellulose E15 solution, and then fabricated by a 3D printer or casting. The 3D printing was accurate and precise in fabricating the ODFs. The SEM micrographs showed that the mirtazapine-printed ODF (3D-MTZ) was porous, with crystals of mirtazapine on the film’s surface. The 3D-MTZ exhibited better mechanical properties than the mirtazapine-casted ODF (C-MTZ), due to the 3D-printing process. The disintegration time of the 3D-MTZ in a simulated salivary fluid, pH 6.8 at 37 °C, was 24.38 s, which is faster than the C-MTZ (46.75 s). The in vitro dissolution study, in 0.1 N HCl at 37 °C, found the 3D-MTZ quickly released the drug by more than 80% in 5 min. This study manifested that 3D-printing technology can potentially be applied for the fabrication of ODF-containing mirtazapine.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040067
Authors: Amir Taldaev Roman P. Terekhov Irina A. Selivanova Denis I. Pankov Maria N. Anurova Irina Yu. Markovina Zhaoqing Cong Siqi Ma Zhengqi Dong Feifei Yang Yonghong Liao
Taxifolin is known as an active pharmaceutical ingredient (API) and food supplement due to its high antioxidant activity, multiple pharmacological effects, and good safety profile. Previously, taxifolin spheres (TS) were obtained from industrially produced API taxifolin in Russia (RT). In our work, we perform a pharmaceutical analysis of this new taxifolin material versus RT. TS is an amorphous material; however, it is stable without the polymer carrier, as confirmed by Fourier transform infrared spectroscopy. Both RT and TS demonstrate high safety profiles and are assigned to Class 1 of the Biopharmaceutical Classification System based on the results of experiments with MDCK cells. The water solubility of the new taxifolin form was 2.225 times higher compared with RT. Hausner ratios for RT and TS were 1.421 and 1.219, respectively, while Carr indices were 29.63% and 19.00%, respectively. Additionally, TS demonstrated sustained release from tablets compared with RT: the half-life values of tablets were 14.56 min and 20.63 min for RT and TS, respectively. Thus, TS may be a promising object for developing oral antiseptics in the form of orally dispersed tablets with sustained release patterns because of its anti-inflammatory, -protozoal, and -viral activities.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040066
Authors: Emmanuel O. Olorunsola Koofreh G. Davies Enomfon B. Essien Mfonobong F. Alozie Musiliu O. Adedokun Fakhrul Ahsan
This work was aimed to assess the antidiabetic effect of orally administered Prosochit®-based nanoparticles of insulin in an animal model. Five batches of insulin-loaded nanoparticles were prepared as dry water-in-oil-in-water emulsions using different emulsifiers (prosopis gum, Prosochit® 201, Prosochit® 101, Prosochit® 102, and chitosan) for the outer emulsion. Unloaded Prosochit® 101-based nanoparticles were also formulated. The morphology and size distribution of the nanoparticles were studied using a scanning electron microscope and Zetasizer. Forty alloxan-induced diabetic Wistar rats were divided into eight groups. The different groups were administered daily with different formulations (unloaded nanoparticles, the 5 loaded nanoparticles equivalent to 50 IU insulin per kg, purified water, and Actrapid) for 14 days. Blood glucose level was monitored and determined over 24 h. Fasting blood sugar was also taken on days 3, 5, 7, and 14. A graph of the percent blood glucose level relative to time 0 h was plotted against time. The particles showed a water-in-oil-in-water constitution. Both the drug-loaded and the unloaded Prosochit®-based nanoparticles were of nano dimension. There was a significant difference (p < 0.0001) in the antidiabetic effects of all insulin-loaded nanoparticles compared with the negative control. There was no significant difference across the insulin-loaded nanoparticles of prosopis gum, Prosochit® 201, Prosochit® 102, and chitosan while the insulin-loaded Prosochit® 101 nanoparticles showed the best activity, which is comparable to subcutaneous insulin, reducing blood glucose levels to 32.20 ± 3.79%. All the oral Prosochit®-based insulin nanoparticles are characterized by appreciable antidiabetic activity with the activity of Prosochit® 101-based nanoformulation being comparable to that of the subcutaneous insulin.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040065
Authors: Marjan Piponski Mariana Horyn Kristina Grncaroska Oleksandra Oleshchuk Elena Petrovska Stefan Angelevski Tetyana Uglyar Tetyana Kucher Liliya Logoyda
Simultaneous determination of the tandem of drugs, like meldonium and metoprolol, with enormous polarity differences between them, requires thorough research and careful selection of chromatographic conditions. The three different CN-cyano groups with link-based particle columns, LiChrospher CN, Waters Spherisorb CNRP, Zorbax CN SB stationary phases, were tested, in an isocratic elution system, with a running mobile phase containing various concepts of composition contents. They were first with buffering salts which included acetonitrile and ammonium phosphate in one group, and then without buffering salts but with diluted acids, composed of acetonitrile and diluted acids as the second group. We can conclude that the most optimal concepts, in terms of expressiveness and environmental friendliness, were concepts using of column Zorbax CN SB (4.6 mm i.d. × 250 mm, 5 μm) and mobile phase ACN—0.15% NH4H2PO4 (50:50 and 60:40, v/v). There are very poor available data about ideas and usable information about the development of methods for simultaneous determination of these two active substances with polarity differences between them. We suggest that our work offered detailed and successful solutions for the mentioned aim using less sophisticated equipment for quality control and a lab for routine manufacturing control.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040064
Authors: Emmanuel Iroha Akubugwo Okezie Emmanuel Celestine Nwabu Ekweogu Ositadinma Chinyere Ugbogu Tochukwu Remigius Onuorah Ozioma Glory Egeduzu Eziuche Amadike Ugbogu
In traditional medicine, Cucurbita pepo L. is used for the treatment of rheumatism, diabetes, inflammations, and wound injuries. This study was conducted to evaluate the phytochemical constituents, safety profile, wound healing, and anti-inflammatory activities of Cucurbita pepo leaf extract in rats. The phytochemical analysis of C. pepo extract was carried out using gas chromatography-mass spectrometry (GC-MS). In acute toxicity tests, the rats orally received a single dose of 5 g/kg extract of C. pepo. In a subacute toxicity study, the rats received 200, 400, and 800 mg/kg of the C. pepo extract via daily gavage for 14 days. Bioactive compounds 1-octen-3-ol, nonanal, trans-β-ionone, phytol, trans-farnesol, and squalene were identified. There were no toxic effects detected in any of the evaluated parameters, namely liver, kidney, haematological, lipid, and antioxidant enzymes. In wound healing, C. pepo extract showed greater % wound contraction and tensile strength, as well as reduced wound healing time (12 days) and epithelialization when compared to the control (normal saline) and povidone-iodine treated groups. Rats treated with C. pepo extract elicit anti-inflammatory activity. The findings of this study revealed that the C. pepo extract has wound healing and anti-inflammatory properties with a wide margin of safety.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040063
Authors: Marcela C. R. Silva Adriana F. L. Vilela Carmen L. Cardoso Ronaldo A. Pilli
In this work, twelve analogues of piperidine alkaloids (-)-cassine and (-)-spectaline were synthesized, as well as the racemic forms of these natural products. The compounds were evaluated for their inhibition of electric eel acetylcholinesterase (AChEee) and human butyrylcholinesterase (BChEhu) by on-flow mass-spectrometry-based dual-enzyme assay, and the inhibition mechanisms for the most potent analogues were also determined. Our results showed a preference for BChEhu inhibition with compounds 10c (Ki = 5.24 μM), 12b (Ki = 17.4 μM), 13a (Ki = 13.2 μM) and 3 (Ki = 11.3 μM) displaying the best inhibitory activities.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040062
Authors: Babak Pakbin Samaneh Allahyari Shaghayegh Pishkhan Dibazar Wolfram Manuel Brück Roghayeh Vahidi Razzagh Mahmoudi Ali Khanjari
Antioxidants are widely used in pharmaceutical industries. Gelatin is a byproduct of the meat industry and its hydrolysates showed several functionalities, such as antioxidant activity. The purpose of this study was to describe and optimize the enzymatic hydrolysis conditions including time, temperature, pH, and enzyme/substrate ratio (E/S) to produce protein hydrolysate with antioxidant functionality from bovine gelatin by RSM; the scavenging activity was evaluated using the DPPH method. The model observed was fitted with desirable adequacy and sufficiency. We found that the antioxidant activity increased significantly (p < 0.05) with the increase in pH value, E/S ratio, and time of enzymatic process; however, the temperature had no significant (p < 0.05) effect on the antioxidant activity of the hydrolysate. The optimum hydrolysis conditions were observed at a temperature of 35.3 °C, pH of 8.0, and E/S ratio at 2.5 after 2 h hydrolysis by trypsin enzyme. The results showed that the hydrolysate under these conditions, optimized by RSM, could be more effective on antioxidant activity. Regarding the antioxidant potential, gelatin hydrolysate can be used as an antioxidant supplement in pharmaceutical industries.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040061
Authors: Ilya Sheferov Alyona Balakireva Dmitry Panteleev Irina Spitskaya Sergey Orekhov Oleg Kazantsev Anna Solovyeva Denis Novopoltsev Nina Melnikova
Zinc oxide nanoparticles (ZnO NPs) modified by oxopyrymidine alcohol, also known as xymedone (Xym), were obtained and studied using FTIR, UV-vis, and fluorescent spectroscopy, and SEM, BET, powder XRD, and DLS analysis. A formulation of thixotropic hydrophilic gels containing Carbopol-based Xym and ZnO NPs was developed. A vertical Franz cell with a cellulose acetate membrane was used as a model to investigate the passive diffusion of the gel components by AAS. The gel components—Xym and ZnO NPs—were shown to penetrate through acetyl cellulose membrane within 5–7 h depending on an initial amount, and its values were in the range of 56–77%. The penetration of modified ZnO NPs by Xym was more effective in contrast to ZnO NPs without modification. The burn wound healing activity of ZnO NPs–Xym gel was demonstrated on a thermal burn wound model on rats. SOD and GR activity was increased by 30–35% during ZnO NPs–Xym gel treatment, the burn area on 10 postburn day decreased by 10% in contrast to a positive control, Methyluracyl®® ointment.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040060
Authors: Nusaiba Al-Nemrawi Fatima Hameedat Tamam El-Elimat
Silver nanoparticles (AgNPs) have broad biocidal activities, and are widely employed as an active ingredient in antiseptic, anti-viral, and anti-inflammatory preparations. Green-synthesizing AgNPs would be a rapid, cheap, and environmentally friendly method of synthesis. The methanolic extract of the leaves of Bellevalia flexuosa Boiss. (Asparagaceae) was used for the green synthesis of the AgNPs. The effects of the pH and the concentration of silver nitrate (AgNO3) on the synthesis of the AgNPs were investigated. The AgNPs produced above pH 10, and 1 mM of AgNO3 resulted in lower hydrodynamic diameters. Ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction proved the formation of the AgNPs, with a face-centered, cubed geometry. Scanning electron microscopy images showed colloidal and well-dispersed nanoparticles. In addition, the antibacterial activities of the prepared AgNPs were assessed by optical densities (ODs) against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus epidermidis) and Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica). The broths of Gram-negative and Gram-positive bacteria that contained AgNPs, showed lower OD values compared to the controls. In conclusion, AgNPs were prepared using B. flexuosa methanolic extract, and showed antibacterial activity against the tested bacterial strains.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040059
Authors: Nichcha Nitthikan Pimporn Leelapornpisid Ornchuma Naksuriya Nutjeera Intasai Kanokwan Kiattisin
This study aimed to investigate the ability of brown Agaricus bisporus extracts to enhance xerosis treatment via their biological activities, including their antioxidant, anti-aging, and anti-inflammation. Brown A. bisporus ethanol extract (EE) and brown A. bisporus water extract (WE) contained ergothioneine and gallic acid as their major compounds, as detected by HPLC, respectively. The WE exhibited the highest total polysaccharide content (734.04 ± 0.03 mg glucose/g extract) and total phenolic content (190.90 ± 0.07 mg gallic acid/g extract). The WE exhibited an inhibitory effect of 83.34 ± 18.66% on a collagenase enzyme, whereas the EE inhibited the elastase enzymes by 81.26 ± 4.37%. In addition, the EE also demonstrated strong activities against DPPH, with an IC50 0.30 ± 0.04 mg/mL, ABTS with a TEAC value of 8.06 ± 0.08 µM Trolox/g extract, and a FRAP assay with a FRAP value of 390.50 ± 0.32 mM FeSO4/g. In addition, all extracts were non-cytotoxic and could decrease the secretion of IL-6 and TNF-α in HaCaT cells. Therefore, brown A. bisporus extracts might be a potential natural raw material that can be further used in cosmeceutical products for xerosis treatment due to their good efficacy.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040058
Authors: Maha M. Azzam Abdelaziz M. Hussein Basma H. Marghani Nashwa M. Barakat Mohsen M. M. Khedr Nabil Abu Heakel
(1) Background: Hepatotoxicity is a common health problem, and oxidative stress plays a crucial role in its underlying mechanisms. We inspected the possible effect of retinoic acid (RA) in the potentiation of hepatoprotective effect of bone marrow mesenchymal stem cells (BM-MSCs) against Cisplatin (Cis)-induced hepatotoxicity. (2) Methods: 60 male Sprague Dawley rats (SD) were separated randomly and designated to six main equal groups as follows: (1) Control group, (2) Cis group (rats got Cis 7 mg/Kg i.p.), (3) Cis + vehicle group (as group 2, but rats received the (vehicle) culture media of BM-MSCs), (4) Cis as in group 2 + BM-MSCs (1x106), (5) Cis as for group 2 + RA 1 mg/Kg i.p., and (6) Cis and BM-MSCs as for group 3 + RA as for group 4. Liver injury was assessed by measuring liver enzymes (ALT, AST), while liver toxicity was evaluated by histopathological examination. Apoptotic marker caspase-3 protein was detected immunohistochemically. Real time PCR was performed to detect NADPH oxidase and TNF-α at transcription levels. Oxidative stress was investigated by colorimetric measurement of MDA, GSH and catalase. (3) Results: Contrary to the Cis group (p < 0.05), BM-MSCs/RA supplementation resulted in a substantial decrease in serum levels of hepatic impairment indicators such as ALT, AST and oxidative stress markers such as MDA, as well as an increase in hepatic GSH, Catalase, and a decrease in expression of TNF-α and downregulation of NADPH oxidase. The improvement after therapy with BM-MSCs/RA was confirmed by histopathological examination. Moreover, the downregulation of caspase-3 in liver tissue after BM-MSCs/RA treatment was validated by immunohistochemistry investigation. (4) Conclusions: BM-MSCs and RA attenuated Cis induced hepatotoxicity through downregulation of oxidative stress resulted in modulation of anti-inflammatory TNF-α and apoptosis caspase-3 indicating a promising role in hepatotoxicity.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90040057
Authors: Subramanian Thangaleela Bhagavathi Sundaram Sivamaruthi Periyanaina Kesika Tanawat Tiyajamorn Muruganantham Bharathi Chaiyavat Chaiyasut
Aromatic essential oils play a significant role in pharmaceuticals, food additives, cosmetics, and perfumery. Essential oils mostly comprise aliphatic hydrocarbons, monoterpenoids, sesquiterpenoids and diterpenes. Plant extracts comprise a complex mixture of terpenes, terpenoids, aliphatic and phenol-derived aromatic components. Terpenes are a significant class of hydrocarbons with numerous health benefits. These biological functions of essential oil components are examined in vitro and in vivo studies. Some studies evaluated the properties and functions of α-phellandrene (α-PHE). Detailed evaluation to determine the functions of α-PHE over a spectrum of health care domains needs to be initiated. Its possible mechanism of action in a biological system could reveal the future opportunities and challenges in using α-PHE as a pharmaceutical candidate. The biological functions of α-PHE are reported, including anti-microbial, insecticidal, anti-inflammatory, anti-cancer, wound healing, analgesic, and neuronal responses. The present narrative review summarizes the synthesis, biotransformation, atmospheric emission, properties, and biological activities of α-PHE. The literature review suggests that extended pre-clinical studies are necessary to develop α-PHE-based adjuvant therapeutic approaches.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030056
Authors: Mariia Mishchenko Sergiy Shtrygol’ Andrii Lozynskyi Mykhailo Hoidyk Dmytro Khyluk Tatyana Gorbach Roman Lesyk
It was determined that the studied 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone (Les-6222) affects the cyclooxygenase pathway of the arachidonic acid cascade, the markers of damage to neurons on models of PTZ kindling. In the model of chronic epileptogenesis in mice (pentylenetetrazole kindling), a 4-thiazolidinone derivative showed high anticonvulsant activity, which is weaker than the effect of sodium valproate and higher than Celecoxib. The mentioned compound has a pronounced anti-inflammatory effect in the brain on the background of the PTZ kindling, reliably inhibiting COX-1 and COX-2. The predominant inhibition of COX-2 by 44.5% indicates this enzyme’s high selectivity of Les-6222. According to the molecular docking study results, the studied compound revealed the properties of COX-1/COX-2 inhibitor and especially 5-LOX/FLAP. The decreasing content of 8-isoprostane in the brain of mice of the Les-6222 group indicates a beneficial effect on cell membranes in the background of oxidative stress during the long-term administration of PTZ. In addition, Les-6222 significantly decreased the content of neuron-specific enolase, indicating neuroprotective properties in the background of chronic epileptogenesis. The obtained results experimentally substantiate the feasibility of further developing Les-6222 as a promising anticonvulsant agent.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030055
Authors: Basanta Kumar Sapkota Karan Khadayat Babita Aryal Jyoti Bashyal Shankar Jaisi Niranjan Parajuli
Globally, obesity is a serious health concern that causes numerous diseases, including type 2 diabetes, hypertension, cardiovascular diseases, etc. Medicinal plants have been used to aid in weight loss since ancient times. Thus, this research is focused on the exploration of pancreatic lipase inhibitory activity and secondary metabolite profiling of Bergenia ciliata, Mimosa pudica, and Phyllanthus emblica, selected based on an ethnobotanical survey. The lipase inhibition was investigated using 4-nitrophenyl butyrate (p-NPB) as a substrate. To uncover further therapeutic potentials of these medicinal plants, antimicrobial activity and minimum inhibitory concentration (MIC) of the extracts were also determined. The ethyl acetate plant extracts showed higher antimicrobial activity against Staphylococcus aureus, Escherichia coli, Salmonella typhi, and Shigella sonnei. The MIC of ethyl acetate extracts of medicinal plants considered in this study ranges from 1.56 to 6.25 mg/mL. The hexane fraction of Mimosa pudica and Phyllanthus emblica showed a higher lipase inhibitory activity as compared to others, with IC50 values of 0.49 ± 0.02 and 2.45 ± 0.003 mg/mL, respectively. In the case of Bergenia ciliata, the methanolic extract inhibited lipase more effectively than others, with an IC50 value of 1.55 ± 0.02 mg/mL (IC50 value of orlistat was 179.70 ± 3.60 µg/mL). A mass spectrometry analysis of various solvent/solvent partition fractions (extracts) revealed 29 major secondary metabolites. The research offers a multitude of evidence for using medicinal plants as antiobesity and antimicrobial agents.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030054
Authors: Hilda Aprilia Wisnuwardhani Slamet Ibrahim Rino R. Mukti Sophi Damayanti
The most challenging step in developing bioanalytical methods is finding the best sample preparation method. The matrix interference effect of biological sample become a reason of that. Molecularly imprinted SERS become a potential analytical method to be developed to answer this challenge. In this article, we review recent progress in MIP SERS application particularly in bioanalysis. Begin with the explanation about molecular imprinting technique and component, SERS principle, the combination of MIP SERS, and follow by various application of MIP SERS for analysis. Finally, the conclusion and future perspective were also discussed.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030053
Authors: Hasan Aldewachi Thamer A. Omar
One of the most prevalent over-the-counter cold and cough medications is the chlorpheniramine maleate (CPM)–ibuprofen (IBF) combination. A reversed-phase high-performance liquid chromatography (RP-HPLC) method was effectively optimized and developed for the simultaneous detection of chlorpheniramine maleate and ibuprofen in a pharmaceutical formulation. The mobile phase for the RP-HPLC method was an isocratic combination of acetonitrile and 0.01 M acetate buffer at pH 3.8 (55:45; v/v) on an Eclipse Plus C18 reversed phase column. An ultraviolet (UV) detector with a wavelength of 225 nm was used to detect the analytes at a flow rate of 1.0 mL/min. CPM and IBF were satisfactorily eluted, with mean retention times of 2.09 and 6.27 min, respectively. The approach was shown to be linear (R2 > 0.9998 for CPM and 0.9992 for IBF), precise (% RSD 3.02% for CPM and 3.48% for IBF), accurate (% recoveries 97.7–98.9% for CPM and 101–104.5% for IBF), specific, easy to use, sensitive, quick, and robust. Limits of detection (LODs) were found to be 10 and 27 μg/mL for CPM and IBF, respectively. Without interference from excipients, the validated method could be utilized in regular quality control analysis of various dosage combinations of hard gelatin capsules containing CPM and IBF.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030052
Authors: Eman M. Mohi El-Deen Eman S. Nossier Eman A. Karam
The present work includes the synthesis of a new series of quinazolin-4(3H)-one compounds (4a–f, 5a–d) as antimicrobial agents. The starting compound, 2-hydrazinylquinazolin-4(3H)-one (2), was synthesized and treated with different carbonyl compounds to afford the hydrazone derivatives 4a–f. In addition, the hydrazone derivatives 4a–d were treated with a DMF/POCl3 mixture to give the formyl-pyrazole derivatives 5a–d. All the target compounds were evaluated as antimicrobial agents against four bacterial and four fungal strains. The majority of the tested compounds showed potent antimicrobial activity compared with the reference antibiotics. The most potent antimicrobial activity was shown by 5a with MIC values in the range (1–16) μg/mL. In addition, the most potent compounds against E. coli were evaluated for their inhibitory activity against E. coli DNA gyrase, whereas the target compounds 4a, 5a, 5c, and 5d showed the most potent inhibition to the target enzyme with IC50 values ranging from 3.19 to 4.17 µM. Furthermore, molecular docking studies were performed for the most active compounds against the target E. coli DNA gyrase to determine their binding affinity within the enzyme’s active site. Moreover, ADME evaluations of these compounds predicted their high oral bioavailability and good GI absorption.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030051
Authors: Srinivas Ajjarapu Srikanth Banda Pratap Basim Narendar Dudhipala
A successful candidate for oral drug delivery needs to possess adequate solubility and dissolution rate to elicit its therapeutic action. Extensive research is being carried out to enhance the solubility of poorly soluble drugs through a number of techniques involving polymeric and non-polymeric approaches. Non-polymeric approaches such as micronization and nanocrystals are successful in improving the apparent solubility of drugs, but the sustenance of solubility is not always possible. Amorphous solid dispersions (ASDs) lead to solubility enhancement as well as the maintenance of solubility with the assistance of polymers, thereby improving bioavailability. Spray drying, hot melt extrusion (HME), and KinetiSol® technologies are some of the techniques capable of manufacturing ASDs. Each of these techniques has its own advantages and disadvantages in terms of processing challenges and applicability in preparing ASDs. The latter two technologies are similar in being fusion and non-solvent techniques to improve solubility. This review compares both HME and KinetiSol® techniques regarding mechanism, equipment design, formulation, and process parameters involved and scalability.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030050
Authors: Nika Andriushchenko Kira Nebogina Yana Zorkina Olga Abramova Eugene Zubkov Aleksandra Ochneva Valeria Ushakova Konstantin Pavlov Olga Gurina Vladimir Chekhonin Anna Morozova
The search for potential effective antidepressants with minimal side effects is necessary. Peptides are possible applicants for this role. We investigated the antidepressant effect of neuropeptide Y (NY), alone and in combination with clomipramine, in models of acute and chronic stress induced by ultrasound of variable frequencies. Rats were divided into the following groups: the control group, stress group, and stress groups with intranasal administration of NY (100 μg/kg) or clomipramine (7.5 mg/kg), or their combination. Rat behavior was evaluated using a sucrose preference test and forced swimming test in an acute stress model, and a sucrose preference test, forced swimming test, social interaction test, open field test, and Morris water maze test in a chronic stress model. The results of our experiment demonstrated a protective effect of intranasal NY in a model of acute stress, which was comparable to the antidepressant effect of clomipramine. When the same dose was chronically administered, NY also demonstrated an antidepressant action, although expressed in a lesser degree than clomipramine. The combination of NY and clomipramine was much less effective in the chronic stress paradigm compared to the separated drug administration, but was just as effective in the acute stress paradigm. Until now, there was no convincing evidence for the efficacy of the chronic administration of neuropeptide Y; we demonstrated its effectiveness in the animal model of depressive-like behavior. However, our hypothesis that neuropeptide Y can enhance the effect of a classical antidepressant was not confirmed.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030049
Authors: Maryna Lieshchova Viktor Brygadyrenko
The pharmacological effects of medicinal plants play a primary role in the mild correction of body weight in humans and animals, reducing the accumulation of fat in their bodies during a state of obesity. Origanum vulgare L. and Scutellaria baicalensis Georgi are widely used as food additives and medicinal plants, but their comprehensive physiological evaluation in model animals in a state of obesity has not been carried out. In a 30-day laboratory experiment on male rats which had developed obesity through a hypercaloric diet, the effects of adding the dry crushed grass O. vulgare or dry crushed roots of S. baicalensis to their feed was evaluated. During the experiment, the rats fed with O. vulgare increased in body weight to only 105.5% of their initial weight, while the body weight of the control group increased to 111.5%, and that of animals fed on S. baicalensis increased to 124.0% of their initial body weight. The average daily increase in the rats’ body weight when O. vulgare was added to their diet decreased to 205 mg/day, and when S. baicalensis was added, on the contrary, it increased to 1417 mg/day, compared to 700 mg/day among the control group. Under the influence of O. vulgare, the lipid metabolism of the rats normalized: the atherogenic index decreased to 33.7%, compared with the values of the control group, due to an increase in the concentration of high-density lipoproteins from cholesterol. The concentration of triglycerides decreased, and the concentration of glucose decreased. The roots of S. baicalensis being added into the diet of rats increased the activity of alkaline phosphatase and decreased the concentration of urea. The atherogenic index also decreased (by up to 35.5% in the control group) and the concentration of high-density lipoprotein cholesterol increased, while the concentrations of triglycerides and glucose decreased. The physical activity of the rats showed a slight tendency to decrease when both O. vulgare and S. baicalensis were added to their diet. Both plant species contributed to a decrease in the emotional status of animals, which was most pronounced when the O. vulgare grass was added to the feed. The results of the study demonstrate the potential of the use of O. vulgare and S. baicalensis as herbal supplementations for the correction of hyperlipidemia and type-2 diabetes mellitus in overweight patients.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030048
Authors: Jeysson Sánchez-Suárez Luisa Villamil Luis Díaz Ericsson Coy-Barrera
The search for novel photoprotective substances has become a challenge in cosmeceutical research. Streptomyces-derived compounds can serve as a promising source of photoprotective agents to formulate skin photoprotection products, such as sunscreens. This study aimed to identify specialized metabolites with the potential to modulate UV-induced cellular damage in the skin by identifying potential multi-target-directed ligands. Using a combination of ligand- and target-based virtual screening approaches, a public compound library comprising 6524 Streptomyces-derived specialized metabolites was studied for their photoprotective capability. The compounds were initially filtered by safety features and then examined for their ability to interact with key targets in the photodamage pathway by molecular docking. A set of 50 commercially available UV filters was used as the benchmark. The protein–ligand stability of selected Streptomyces-derived compounds was also studied by molecular dynamics (MD) simulations. From the compound library, 1981 compounds were found to meet the safety criteria for topically applied products, such as low skin permeability and low or non-toxicity-alerting substructures. A total of 34 compounds had promising binding scores against crucial targets involved in UV-induced photodamage, such as serotonin-receptor subtype 5-HT2A, platelet-activating factor receptor, IL-1 receptor type 1, epidermal growth factor receptor, and cyclooxygenase-2. Among these compounds, aspergilazine A and phaeochromycin F showed the highest ranked interactions with four of the five targets and triggered complex stabilization over time. Additionally, the predicted UV-absorbing profiles also suggest a UV-filtering effect. Streptomyces is an encouraging biological source of compounds for developing topical products. After in silico protein–ligand interactions, binding mode and stabilization of aspergilazine A and phaeochromycin F led to the discovery of potential candidates as photodamage multi-target inhibitors. Therefore, they can be further explored for the formulation of skin photoprotection products.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030047
Authors: Suriyan Thengyai Yuewei Guo Khanit Suwanborirux Heinz Berner Helmut Spreitzer Peter Wolschann Supa Hannongbua Anuchit Plubrukarn
A series of scalarane sesterterpenes were prepared using heteronemin (1) as a primary precursor. Combined with the scalarane derivatives obtained from natural sources, a total of 22 antitubercular scalaranes were used to build QSAR models based in the 2D-QSAR and CoMFA approaches. Both models indicated the influences of substitutions in the vicinity of C-12 and C-16 of the scalaranes. A 2D-QSAR model suggested the necessity of hydrophilic functionalities on the peripherals with hydrophobic cores, and the lowering steric repulsion to improve the potential energy. This was complemented by the pictorial CoMFA model, which indicated the importance of the positive electrostatic with shortened steric extension crowning over C-12 and the lengthy negative functionalities extended from C-16.
]]>Scientia Pharmaceutica doi: 10.3390/scipharm90030046
Authors: Edward A. Wetzel Grace C. Corriero Sandra Brown-Ford Daniel S. Sem William A. Donaldson
Estrogen receptors (ER) are nuclear hormone receptors which are responsible for sex hormone signaling in women. A series of (1,4-disubstituted)-1,2,3-triazoles 5–21 were prepared by reaction of azidophenols with terminal alkynes under Fokin reaction conditions. The products were purified by column chromatography or recrystallization and characterized by NMR and HRMS. The compounds were tested for binding to ERβ via a ligand displacement assay, and 1-(4-hydroxyphenyl)-α-phenyl-1,2,3-triazole-4-ethanol (21) was found to be the most potent analog (EC50 = 1.59 μM). Molecular docking of 5–21 within the ligand binding pocket of ERβ (pdb 2jj3) was performed and the docking scores exhibited a general qualitative trend consistent with the measured EC50 values.
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