PDF(Pubmed)
Abstract：
Androgenic alopecia (AGA) is a dermatological disease with psychosocial consequences for those who experience hair loss. AGA is linked to an increase in androgen levels caused by an excess of dihydrotestosterone in blood capillaries produced from testosterone by 5α-reductase type II (5αR2), which is expressed in scalp hair follicles; 5αR2 activity and dihydrotestosterone levels are elevated in balding scalps. The diverse health benefits of flavonoids have been widely reported in epidemiological studies, and research interest continues to increase. In this study, a virtual screening approach was used to identify compounds that interact with active site residues of 5αR2 by screening a library containing 241 flavonoid compounds. Here, we report two potent flavonoid compounds, eriocitrin and silymarin, that interacted strongly with 5αR2, with binding energies of -12.1 and -11.7 kcal/mol, respectively, which were more significant than those of the control, finasteride (-11.2 kcal/mol). Molecular dynamic simulations (200 ns) were used to optimize the interactions between compounds and 5αR2 and revealed that the interaction of eriocitrin and silymarin with 5αR2 was stable. The study shows that eriocitrin and silymarin provide developmental bases for novel 5αR2 inhibitors for the management of AGA.
摘要：
雄激素性脱发（AGA）是一种皮肤病，对那些经历脱发的人具有心理社会后果。AGA与由II型5α-还原酶（5αR2）产生的睾丸激素产生的毛细血管中二氢睾丸激素过量引起的雄激素水平升高有关，在头皮毛囊中表达；秃顶头皮中5αR2活性和二氢睾酮水平升高。黄酮类化合物的多种健康益处已在流行病学研究中得到广泛报道,研究兴趣不断提高。在这项研究中,通过筛选含有241个类黄酮化合物的文库,采用虚拟筛选方法鉴定与5αR2活性位点残基相互作用的化合物.这里,我们报告了两种有效的类黄酮化合物，毛皮和水飞蓟素，与5αR2强烈相互作用，结合能为-12.1和-11.7kcal/mol，分别,比对照组更重要，非那雄胺（-11.2千卡/摩尔）。使用分子动力学模拟（200ns）来优化化合物与5αR2之间的相互作用，并揭示了麦草苷和水飞蓟素与5αR2的相互作用是稳定的。该研究表明，赤霉素和水飞蓟素为新型5αR2抑制剂管理AGA提供了开发基础。
