Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Obstetrics and Gynecology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Bioengineered. 2021 Dec;12(2):10345-10362. doi: 10.1080/21655979.2021.1996317.
Bushen Huoxue (BSHX) has been applied in clinical traditional Chinese medicine treatment, and has definitive clinical efficacy in the treatment of Premature Ovarian Insufficiency (POI) in China. However, little is known of the underlying mechanism of BSHX. The purpose of this paper is to study the pharmacological mechanisms of BSHX acting on POI based on a pharmacology and experimental validation. The pharmacological database of chinese medicine system and analysis platform (TCMSP) were used to search the effective active ingredients and potential action targets of BSHX. Drugbank, Online Mendelian Inheritance in Man (OMIM), Genecards, and Disgenet databases were used to obtain relevant targets of POI. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and the visual network of protein-protein interaction network were constructed by FunRich3.1. Pymol software, and Auto Dock tools 1.5.6 were used for molecular docking. Murine model of POI was used to further investigate the mechanism of BSHX against on POI. Finally, 127 active compounds were collected from TCMSP database, and 215 active targets were identified. There were 1366 targets related to POI and 99 targets of BSHX for the treatment of POI. Quercetin, kaempferol, and stigmasterol were recognized as the most effective compounds corresponding to targets. The top three genes according to degree value are TP53, Akt1, and VEGFA. Further, the results of GO and KEGG enrichment analysis revealed that those core targets were mainly enriched on TRAIL and TGF-β receptor signaling. The results of molecular docking showed that stigmasterol had good binding ability to Akt1. Moreover, experimental validation suggests that BSHX significantly Increased the expression of TGF-β1 and Smad2/3, regulating the release of serum sex hormones, which include Follicular stimulating hormone (FSH), Estradiol (E2), and Antimullerin hormone (AMH).
补肾活血（BSHX）已应用于临床中医治疗，在中国治疗卵巢早衰（POI）方面具有明确的临床疗效。然而，BSHX 的潜在作用机制知之甚少。本文旨在基于药理学和实验验证研究 BSHX 作用于 POI 的药理机制。采用中药系统药理学数据库和分析平台（TCMSP）搜索 BSHX 的有效活性成分和潜在作用靶点。Drugbank、Online Mendelian Inheritance in Man（OMIM）、Genecards 和 Disgenet 数据库用于获得 POI 的相关靶点。使用 FunRich3.1 构建基因本体（GO）富集、京都基因与基因组百科全书（KEGG）通路富集和蛋白质-蛋白质相互作用网络可视化网络。使用 Pymol 软件和 Auto Dock tools 1.5.6 进行分子对接。建立 POI 小鼠模型进一步研究 BSHX 治疗 POI 的机制。最后，从 TCMSP 数据库中收集了 127 种活性化合物，鉴定出 215 个活性靶点。有 1366 个与 POI 相关的靶点和 99 个与 BSHX 治疗 POI 相关的靶点。槲皮素、山奈酚和豆甾醇被认为是对应靶点最有效的化合物。根据度值排名前三位的基因是 TP53、Akt1 和 VEGFA。此外，GO 和 KEGG 富集分析的结果表明，这些核心靶点主要富集在 TRAIL 和 TGF-β 受体信号通路。分子对接的结果表明，豆甾醇与 Akt1 具有良好的结合能力。此外，实验验证表明，BSHX 可显著增加 TGF-β1 和 Smad2/3 的表达，调节血清性激素的释放，包括卵泡刺激素（FSH）、雌二醇（E2）和抗苗勒管激素（AMH）。
