目的 探索桂枝茯苓胶囊治疗痛经、子宫肌瘤和盆腔炎的分子作用机制和潜在活性成分群。方法 通过文献挖掘、多个数据库联用检索与痛经、盆腔炎以及子宫肌瘤疾病相关的130个靶蛋白基础上,利用分子计算结合网络特征分析获得桂枝茯苓胶囊的主要活性成分和潜在的靶点蛋白,并将其投射到KEGG数据库阐释桂枝茯苓胶囊的分子作用机制。结果 数据分析结果表明,与蛋白相互作用较强的115个活性分子主要分布在桂枝和茯苓中,进一步的网络特征分析发现高网络度和介数的分子主要为五环三萜类和甾醇类化合物;与化合物作用的绝大部分靶蛋白(78.57%)分布在与痛经、盆腔炎及子宫肌瘤密切相关的15条生物通路中,而这些通路涉及到子宫平滑肌的增殖和收缩,子宫内的血管形成和血液循环,雌激素和黄体酮等多种激素的分泌,以及前列腺素等炎症因子合成或释放和相关钙通道的调控等。结论 桂枝茯苓胶囊主要是由其所含的五环三萜类和甾醇类化合物与多个靶点蛋白作用,调控多条生物通路(如arachidonic acid metabolism,calcium signaling pathway,GnRH signaling pathway,complement and coagulation cascades,progesterone-mediated oocyte maturation)来抑制子宫平滑肌收缩和增殖、改善微循环、降低激素分泌和炎症反应(如PGF₂,PGF_2α,leukotriene B4),从而起到缓解痛经和盆腔炎引起的疼痛、改善子宫肌瘤患者的生活质量的作用。

Objective To investigate the molecular maechanism and potential active constituents population of Guizhi Fuling Capsule(GFC) for the treatment of dysmenorrhea, pelvic inflammatory disease(PID), and hysteromyoma. Methods One handred and thirty target proteins related with dysmenorrhea, PID, and hysteromyoma were selected through mining literature, retrieving in DrugBank and TTD database, the main active constituents and potential target proteins from GFC were computed and analyzed by DOVIS2.0 and Cytoscape 3.0. The potential target proteins were then projected into the KEGG databases to illustrate the molecular mechanism of GFC. Results The results of data analysis showed that the 115 active molecules with stronger interaction with protein were distributed in Cinnamomi Ramulus and Poria. The High network degree and betweenness of molecules were found to be pentacyclic triterpenes and steroids by further analysis of network characteristics. The most of the potential target proteins(78.57%) interacted wth the compounds in GFC were from 15 biological pathways closely related with dysmenorrhea, PID, and hysteromyoma in KEGG database, which was involved in cell proliferation, angiogenesis, coagulation, dysregulation of inflammatory process, uterine contractions, and release of estrogen or progesterone in uterus. As well as the synthesis or release of inflammatory factors such as prostaglandin and the regulation of calcium channels and so on. Conclusion GFC has the function by the interaction of pentacyclic triterpenes and steroids with multi target proteins, such as arachidonic acid metabolism, calcium signaling pathway, GnRH signaling pathway, complement and coagulation cascades, and progesterone-mediated oocyte maturation, to alleviate the pain of dysmenorrhea and PID, or improve the quality of life for the patients with hysteromyoma through inhibiting uterine contractions, improving microcirculation, and reducing the release of estrogen or promegestone and inflammatory response(such as PGF₂, PGF_2α, and leukotriene B4).

国家重大新药创制——现代中药创新集群与数字制药技术平台(2013ZX09402203)