In Vivo and In Silico Evaluation of Citrus sinesis Peel Extracts on Oxidative Stress, Inflammation and Hormonal Parameters in Testosterone Induced Benign Prostate Hyperplasia in Male Wistar Rats
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Date
2023-12
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Lead City University
Abstract
Benign prostate hyperplasia (BPH) is a noncancerous enlargement of the prostate gland that makes urinating challenging. Citrus sinesis peel (CSP) has been reported to have antioxidant, anti-inflammatory, and antitumour properties. This study investigated the in vivo and in silico effects of CSP extracts on testosterone-induced Benign Prostate Hyperplasia (BPH). Forty-eight rats were randomized into eight groups of six animals each: non-castrated control, castrated control, castrated rats that received testosterone propionate (TP) subcutaneously, castrated rats received TP and 250mg/kg MECSP, castrated rats that received TP and 500mg/kg MECSP, castrated rats that received TP and 250mg/kg HECSP, castrated rats that received TP and
500mg/kg HECSP and castrated rats that received TP and Dutasteride (standard drug). Molecular docking analysis was conducted using Autodock Vina from PyRX. Results indicated that BPH rats had significantly (p < 0.05) increased relative organ weight, 5α-reductase activity and MDA levels in serum, prostate and liver in the BPH rats and oxidative stress biomarkers were altered significantly. Liver enzyme activities (AST and ALT) and inflammatory markers (PPARα and NFkB) were significantly increased in the serum of the BPH rats. There was significant reduction in testosterone, progesterone and Luteinizing hormone and histology of the prostate revealed hyperplasia. Treatment with MECSP, HECSP and Dutasteride, respectively attenuated
these changes. GC-MS analysis showed 40 compounds in MECSP and 34 compounds in HECSP. Molecular docking shows that interaction of compounds from MESCP with 5α-reductase and Prostrate specific membrane antigen. Cholestan-7-one, cyclic 1, 2-ethanediol acetal, (5.alpha.) and Vitamin E had the highest binding affinities for 5α-reductase and 4H-1-Benzopyran-4-one, 2-(1,3- benzodioxol-5-yl)-5,7-dimethoxy-and Vitamin E had the highest binding affinity for prostate- specific membrane antigen. CSP extracts elicited protective effects on BPH via restoring the relative organ weight, 5α-reductase activity, biomarkers of oxidative stress, inflammatory biomarkers, and hormonal parameters. These extracts contain bioactive compounds that might be chemopreventive against Benign prostate hyperplasia.
Keywords: Benign prostate hyperplasia, citrus sinesis peel, 5α-reductase, in silico, oxidative stress
Word Count: 300
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Keywords
Benign prostate hyperplasia, citrus sinesis peel, 5α-reductase, in silico, oxidative stress
Citation
Kate Turabian