基于系统药理学和分子对接探讨青娥丸治疗绝经后骨质疏松症的作用机制

目的从分子层面探讨青娥丸治疗绝经后骨质疏松症的作用机制,并探索青娥丸的潜在治疗靶点。方法利用TCMSP及BATMAN-TCM数据库筛选青娥丸的化合物成分,随后在PharmMapper数据库进行潜在靶点识别。通过Gene Cards、PubMed及CTD数据库,检索绝经后骨质疏松症的相关靶点。而后使用David软件对青娥丸作用于绝经后骨质疏松症的关键靶点进行GO富集及KEGG通路富集分析,运用Bio GPS数据库对关键靶点进行器官定位,利用i GEMDOCK软件进行分子对接分析。结果通过网络药理学方法分析青娥丸的4味中药,发现其有效化学成分32个,对应100个作用靶点;通过GO分析,45个关键靶点富集出150个生物学过程、28个细胞组成及38个分子功能;通过KEGG分析得出关键靶点显著富集的信号通路有36条;通过Bio GPS软件进行器官定位分析,发现靶点富集于肺、肝、心、肾和卵巢等5个关键器官;通过分子对接分析发现关键靶点CYP3A4与主要化合物hirsutin_qt有较高结合度。结论青娥丸具有多成分、多靶点的作用特点,并通过参与多种生物过程,调控多条信号通路,调节多个组织器官以干预绝经后骨质疏松症发挥其药理疗效。

Study on the mechanism of Qing'e pill in the treatment of postmenopausal osteoporosis based on systemic pharmacology and molecular docking

Objective To explore the molecular mechanism of Qing''e pill in the treatment of postmenopausal osteoporosis, and to explore the potential therapeutic target of Qing''e pill. Methods TCMSP and BATMAN-TCM database were used to screen the compounds of Qing''e pill. The potential targets were identified in the PharMapper database. The related targets of postmenopausal osteoporosis were searched through GeneCards, PubMed, and CTD database. David software was used to perform the GO enrichment and KEGG pathway enrichment analysis on the key targets of Qing''e pill acting on postmenopausal osteoporosis. The key targets were located with the BioGPS database, and the molecular docking analysis was carried out with iGEMDOCK software. Results There were 32 effective chemical components, corresponding to 100 targets, through the network pharmacology analysis of 4 traditional Chinese medicines in Qing''e pill. 150 biological processes, 28 cell components, and 38 molecular functions were found through the GO analysis. 36 signal pathways with significant target enrichment were found through the KEGG analysis. The targets were enriched in the lung, liver, heart, kidney, and ovary through the organ positioning analysis with the bBioGPS software. Through molecular docking analysis, it was found that the key target of CYP3A4 had a high binding degree with hirsutin_qt. Conclusion Qing''e pill has the multi-component and multi-target characteristics. It can play its pharmacological role in regulating multiple signal pathways, regulating multiple tissues and organs by participating in a variety of biological processes to interfere postmenopausal osteoporosis.