School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Drug Des Devel Ther. 2021 May 17;15:2059-2089. doi: 10.2147/DDDT.S307015. eCollection 2021.
One of the most common types of male infertility is recognized as oligoasthenozoospermia (OA), characterized by low sperm count and quality in males. As a traditional Chinese medicine (TCM), coupled-herbs (CSMFCH) has been known to act a curative effect on OA for thousands of years. Nevertheless, the substantial basis and molecular mechanism of CSMFCH in treating OA remain elusive.
Herein, an integrated approach, including network pharmacology, molecular docking, and experiment validation, was utilized to reveal the new candidate active component and mechanism of CSMFCH in treating OA.
The results show that kaempferol is the most significant bioactive component of CSMFCH on OA. The mechanism and targets of CSMFCH against OA are relevant to hormone regulation, oxidant stress, and reproductive promotion. In order to validate network pharmacology results, molecular docking and experiment validation were conducted. In detail, molecular docking was employed to verify the strong binding interactions between kaempferol and the core targets. UHPLC-Q-Orbitrap-MS was used to identify kaempferol in the CSMFCH extract. In vitro and in vivo experiments further proved CSMFCH and kaempferol could enhance the mouse Leydig (TM3) and mouse Sertoli (TM4) cell viability, improve the male reproductive organ weights, sperm quality, and decrease testis tissue damage in the OA mouse model induced by CP.
Our results not only identify the new candidate active component of CSMFCH in treating OA but also provide new insights into the mechanisms of CSMFCH against OA.
男性不育症最常见的类型之一是少精子症（OA），其特征是男性精子数量和质量低。作为一种中药（TCM），复方生精汤（CSMFCH）几千年来一直被认为对 OA 有治疗作用。然而，CSMFCH 治疗 OA 的实质性基础和分子机制仍不清楚。
本研究采用网络药理学、分子对接和实验验证相结合的方法，揭示 CSMFCH 治疗 OA 的新候选活性成分和作用机制。
结果表明，山奈酚是 CSMFCH 治疗 OA 的最重要的生物活性成分。CSMFCH 治疗 OA 的机制和靶点与激素调节、氧化应激和生殖促进有关。为了验证网络药理学的结果，进行了分子对接和实验验证。具体来说，采用分子对接验证了山奈酚与核心靶点之间的强结合相互作用。采用 UHPLC-Q-Orbitrap-MS 鉴定了 CSMFCH 提取物中山奈酚的存在。体外和体内实验进一步证明 CSMFCH 和山奈酚可以提高 OA 模型小鼠睾丸间质细胞（TM3）和支持细胞（TM4）的活力，增加雄性生殖器官重量，改善精子质量，并减少 CP 诱导的 OA 小鼠睾丸组织损伤。
本研究不仅鉴定了 CSMFCH 治疗 OA 的新候选活性成分，还为 CSMFCH 治疗 OA 的机制提供了新的见解。
