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 prescription 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.