Systems Pharmacology Uncovers Multiple Mechanisms of Erxian Decoction (二仙汤) for Treatment of Premature Ovarian Failure

Objective: To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction(二仙汤,EXD) as a treatment for premature ovarian failure(POF) using a systems pharmacology approach. Methods: The compounds present in EXD were obtained from three databases. The active ingredient was identified by analyzing the values of oral bioavailability(OB), drug-likeness(DL), and Lipinski's rule(LR). The active ingredients were further searched in research articles, drug targets in the Drug Bank database, and the C-T and T-P networks, as well as by pathway analysis using the Cytoscape platform. Results: A total of 728 compounds were identified in EXD. Of these, 59 were identified as active compounds that conformed to the criteria with OB 30% and DL 0.18. By further searches in the literature, 126 related targets were identified that could interact with the active compounds. Additionally, it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immune system, modulation of estrogen levels, and anti-oxidative activities, and that it may act in a synergistic or cooperative manner with other therapeutic agents. Conclusions: The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF. The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.