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.