Molecular mechanism of Guizhi Fuling Capsule for treatment of dysmenorrhea, pelvic inflammatory disease, and hysteromyoma via network pharmacology / 中草药

ABSTRACT

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 PGE2, PGF2α, and leukotriene B4).