A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Zuogui Yin in the Treatment of Male Infertility

Background and Aim: Traditional Chinese medicine (TCM), as a complementary and alternative therapy, has played increasingly important roles in clinical treatment and disease prevention. Zuogui Yin (ZGY) is one of the well-known TCM prescriptions used for the treatment of male infertility. To fully reveal the potential mechanisms underlying the therapeutic effects of ZGY on male infertility, a network pharmacology approach was conducted at the molecular level. Methods: Network pharmacology approach was used in this study, which mainly included active compound screening, target prediction, gene enrichment analysis, and network analysis. Results: The network analysis successfully identified 148 potential active ingredients of ZGY and 155 predicted targets that were associated with male infertility. ZGY might play a role in the treatment of male infertility by regulating ten hub targets (VEGFA, CASP3, TNF, AKT1, EGF, EGFR, IL-6, MAPK1, TP53, and PTGS2) and six pathways (TNF signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Toll-like receptor signaling pathway, VEGF signaling pathway, and MAPK signaling pathway). Conclusion: This study explored the pharmacological activity and molecular mechanisms of ZGY against male infertility from a holistic perspective. The underlying molecular mechanisms were closely related to the intervention of oxidative stress and apoptosis with CASP3, TP53, AKT1, and MAPK1 being possible targets.