Ebenyi Lilian N, Chigozie Victor U, Destiny Demian, Anyanwu Chidinma B
Department of Biotechnology, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria.
Department of Pharmaceutical Microbiology and Biotechnology, David Umahi Federal University of Health Sciences, Uburu, Ebonyi State, Nigeria.
Nat Prod Res. 2024 Sep 28:1-8. doi: 10.1080/14786419.2024.2409384.
Benign prostate hyperplasia (BPH) remains one of the major age-related urological problems in the world. (soursop) leaf has been reported to exhibit antiproliferative, antioxidant, and anti-inflammatory activities, among others, in the literature. Here, we aimed to unravel the antioxidative, antiandrogenic, and inhibitory activities of the ethanol extract of leaf (EEAML) on sex hormones-induced benign prostate hyperplasia (BPH) through and studies. Thirty-six male rats were segmented into six groups of six animals each, the control group received water, and the BPH group and the remaining four groups were parentally infused with testosterone (T) and oestradiol (E2) (0.08 and 0.04 mg/Kgbwt) once daily for 28 days to induce BPH. After that, the control and BPH groups received water and normal saline, while the remaining four groups received finasteride (FIN) (0.1 mg/kgbwt) and EEAML (200, 400, and 800 mg/kgbwt) for another 28 days before sacrifice, and serum was collected for biochemical analysis. Additionally, the active ingredients of EEAML were identified using a Gas Chromatography Flame Ionisation Detector (GC-FID) followed by molecular docking (MD) against the human androgen receptor (hAR) target, and ADMET analysis of selected EEAML compounds was carried out. EEAML (200, 400, and 800 mg/kgbwt) restored the T and E2-induced depletion of reduced glutathione level, superoxide dismutase and catalase activities, and elevation of malondialdehyde, prostate-specific antigen, testosterone, and dihydrotestosterone levels in the serum of BPH rats. GC-FID analysis of EEAML showed the presence of 21 compounds from which 15 compounds were subjected to MD revealing that flavone, followed by ribalinidine, flavonone, anthocyanin, and naringenin displayed desirable binding affinities against the hAR target. ADMET analysis of these top-five EEAML compounds revealed that they were excellent oral bioavailable drug candidates with predicted minimal toxicities. In conclusion, EEAML exhibited antioxidative, antiandrogenic, and inhibitory activities owing to its phytoconstituents, which in turn could serve as drug templates for much better efficacy.
良性前列腺增生(BPH)仍然是世界上主要的与年龄相关的泌尿系统问题之一。文献报道,(刺果番荔枝)叶具有抗增殖、抗氧化和抗炎等活性。在此,我们旨在通过体内和体外研究,揭示刺果番荔枝叶乙醇提取物(EEAML)对性激素诱导的良性前列腺增生(BPH)的抗氧化、抗雄激素和抑制活性。将36只雄性大鼠分成6组,每组6只动物,对照组给予水,BPH组和其余4组每天经腹腔注射睾酮(T)和雌二醇(E2)(0.08和0.04mg/Kgbwt),持续28天以诱导BPH。之后,对照组和BPH组给予水和生理盐水,而其余4组在处死前再给予非那雄胺(FIN)(0.1mg/kgbwt)和EEAML(200、400和800mg/kgbwt),持续28天,然后收集血清进行生化分析。此外,使用气相色谱火焰离子化检测器(GC-FID)鉴定EEAML的活性成分,随后针对人雄激素受体(hAR)靶点进行分子对接(MD),并对选定的EEAML化合物进行ADMET分析。EEAML(200、400和800mg/kgbwt)恢复了T和E2诱导的BPH大鼠血清中还原型谷胱甘肽水平、超氧化物歧化酶和过氧化氢酶活性的降低,以及丙二醛、前列腺特异性抗原、睾酮和双氢睾酮水平的升高。EEAML的GC-FID分析显示存在21种化合物,其中15种化合物进行了MD分析,结果表明黄酮,其次是利巴利定、黄酮酮、花青素和柚皮苷对hAR靶点表现出理想的结合亲和力。对这5种EEAML化合物的ADMET分析表明,它们是具有优异口服生物利用度且预测毒性最小的候选药物。总之,EEAML由于其植物成分而表现出抗氧化、抗雄激素和抑制活性,这反过来可以作为具有更好疗效的药物模板。