目的 基于分子对接及分子动力学模拟方法从中药活性成分中寻找潜在的II型5α-还原酶（5αR2）抑制剂。方法 采用分子对接方法对中药来源的26种单体成分进行对接，根据对接结果，对与蛋白结合较强的化合物进行分子动力学模拟，采用MM/PBSA方法计算体系的结合自由能；通过体外微量酶反应体系进行生物活性验证。结果 26种单体成分与5αR2具有不同程度的结合能，其中女贞苷、红花黄色素和扁柏双黄酮的结合能较低，结合能力强；分子动力学模拟结果与对接结果相一致（结合能力：女贞苷-蛋白 > 红花黄色素-蛋白 > 扁柏双黄酮-蛋白）；活性实验结果显示3种成分对5αR2具有一定的抑制作用，女贞苷半数抑制浓度（IC₅₀）值为（42.12±3.83）μmol/L，红黄黄色素IC₅₀值为（69.06±6.35）μmol/L，扁柏双黄酮IC₅₀值为（191.28±5.90）μmol/L。结论 筛选的26个单体成分中，女贞苷、红花黄色素和扁柏双黄酮具有预防和治疗雄激素依赖型疾病新药研发的潜力，为探索新型5αR2抑制剂提供参考。

Objective To screen the potential type II 5α-reductase inhibitors from active ingredients of traditional Chinese medicine (TCM) based on molecular docking and molecular dynamics (MD) simulation technology. Methods The molecular docking was used to screen 26 monomer compositions from TCM. Based on the docking results, MD was performed to evaluate the binding strength of compounds with protein. The binding free energy of the system was calculated using the MM/PBSA method. The in vitro micro-reaction system was used to investigate biological activity. Results The binding energies of 26 monomer compositions from TCM to type II 5-alpha Reductase were different. Among them, ligustroflavone, safflower yellow and hinokiflavone have low binding energies to type II 5-alpha reductase, and their binding abilities were strong. The molecular dynamics simulation results are consistent with the docking results (binding capacity:ligustroflavone-protein > safflower yellow-protein > hinokiflavone-protein). The three components ligustroflavone, safflower yellow and hinokiflavone have a certain inhibitory activity on type II 5α-reductase with the IC₅₀ value of (42.12±3.83), (69.06±6.35), and (191.28±5.90) μmol/L, respectively. Conclusion Among the screened 26 monomer compositions, ligustroflavone, safflower yellow and hinokiflavone have the potential to be used in the study of treatment and prevention of androgen-dependent diseases, which provides a reference for further exploration and discovery of type II 5α-reductase inhibitors.

广东省科技厅应用型研发专项（2015B020234009）；国家重点研发计划"中医药现代化"重点专项项目（2018YFC1707100）