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1.
Behav Brain Res ; 466: 114976, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38599249

ABSTRACT

Although there are various treatments available for depression, some patients may experience resistance to treatment or encounter adverse effects. Centella asiatica (C. asiatica) is an ancient medicinal herb used in Ayurvedic medicine for its rejuvenating, neuroprotective and psychoactive properties. This study aims to explore the antidepressant-like effects of the major constituents found in C. asiatica, i.e., asiatic acid, asiaticoside, madecassic acid, and madecassoside at three doses (1.25, 2.5, and 5 mg/kg, i.p), on the behavioural and cortisol level of unpredictable chronic stress (UCS) zebrafish model. Based on the findings from the behavioural study, the cortisol levels in the zebrafish body after treatment with the two most effective compounds were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, a molecular docking study was conducted to predict the inhibitory impact of the triterpenoid compounds on serotonin reuptake. The in vivo results indicate that madecassoside (1.25, 2.5, and 5 mg/kg), asiaticoside and asiatic acid (5 mg/kg) activated locomotor behaviour. Madecassoside at all tested doses and asiaticoside at 2.5 and 5 mg/kg significantly decreased cortisol levels compared to the stressed group, indicating the potential regulation effect of madecassoside and asiaticoside on the hypothalamic-pituitary-adrenal axis overactivity. This study highlights the potential benefits of madecassoside and asiaticoside in alleviating depressive symptoms through their positive effects on behaviour and the hypothalamic-pituitary-adrenal (HPA)- axis in a chronic unpredictable stress zebrafish model. Furthermore, the in silico study provided additional evidence to support these findings. These promising results suggest that C. asiatica may be a valuable and cost-effective therapeutic option for depression, and further research should be conducted to explore its potential benefits.


Subject(s)
Antidepressive Agents , Centella , Molecular Docking Simulation , Pentacyclic Triterpenes , Triterpenes , Zebrafish , Animals , Triterpenes/pharmacology , Centella/chemistry , Antidepressive Agents/pharmacology , Pentacyclic Triterpenes/pharmacology , Hydrocortisone/metabolism , Disease Models, Animal , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Depression/drug therapy , Behavior, Animal/drug effects , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Biomarkers/metabolism , Male
2.
Infect Disord Drug Targets ; 22(7): 49-55, 2022.
Article in English | MEDLINE | ID: mdl-35532251

ABSTRACT

BACKGROUND: Fourier Transform Infrared (FTIR) spectroscopy and reverse phase highperformance liquid chromatography, RP-HPLC analysis have been used for the quantitative determination of local l commercially available Pitavastatin products. METHODS: The FTIR method of analysis is not widely used in pharmaceutical quality control laboratories. This technique is non-destructive, reliable, precise, and efficient, and the samples can be prepared easily. These features emphasized that the FTIR technique can be considered as a potential analytical method for quantitative analysis in pharmaceutical laboratories. RESULTS: It is strongly recommended that FTIR analytical method can be applied simultaneously with RP-HPLC techniques for quality control purposes of drug analysis. Both methods of analysis have shown comparable precision and good repeatability and reproducibility for analysis of Pitavastatin which can be generalized for other pharmaceutical products. CONCLUSION: In addition, FTIR is not only used for the determination of vibrational modes and structure in the fingerprint region, but it can be also generally applied in quantitative analysis for many pharmaceutical products.

3.
Curr Drug Discov Technol ; 18(2): 317-332, 2021.
Article in English | MEDLINE | ID: mdl-32208118

ABSTRACT

AIMS AND OBJECTIVE: In this study, a novel quantitative structure activity relationship (QSAR) model has been developed for inhibitors of human 5-alpha reductase type II, which are used to treat benign prostate hypertrophy (BPH). METHODS: The dataset consisted of 113 compounds-mainly nonsteroidal-with known inhibitory concentration. Then 3D structures of compounds were optimized and molecular structure descriptors were calculated. The stepwise multiple linear regression was used to select descriptors encoding the inhibitory activity of the compounds. Multiple linear regression (MLR) was used to build up the linear QSAR model. RESULTS: The results obtained revealed that the descriptors which best describe the activity were atom type electropological state, carbon type, radial distribution function (RDF), barysz matrix and molecular linear free energy relation. The suggested model could achieve satisfied square correlation coefficient of R2 = 0.72, higher than of many previous studies, indicating its superiority. Rigid validation criteria were met using external data with Q2 ˃ 0.5 and R2 = 0.75, reflecting the predictive power of the model. CONCLUSION: The QSAR model was applied for screening botanical components of herbal preparations used to treat BPH, and could predict the activity of some, among others, making reasonable attribution to the proposed effect of these preparations. Gamma tocopherol was found to be an active inhibitor, in consistence with many previous studies, anticipating the power of this model in the prediction of new candidate molecules and suggesting further investigations.


Subject(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase , 5-alpha Reductase Inhibitors/pharmacology , Membrane Proteins , Prostatic Hyperplasia , Quantitative Structure-Activity Relationship , gamma-Tocopherol/pharmacology , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , Dihydrotestosterone/metabolism , Drug Discovery , Humans , Isoenzymes , Male , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/metabolism , Plant Preparations/pharmacology , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/metabolism
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