Network Pharmacology Approach for Predicting Targets of Zishen Yutai Pills on Premature Ovarian Insufficiency

Background and Purpose. Premature ovarian insufficiency (POI) is a serious reproductive disease in females that is characterized by menstrual and ovulation disorders and infertility. The clinical efficacy of complementary and alternative medicine (CAM) has been reported in POI, including compound Chinese medicine. Zishen Yutai Pills (ZSYTP), a well-known patented Chinese medicine, has been widely used for treating POI; however, the pharmacological mechanism and molecular targets of ZSYTP remain unknown. Here, we systematically elucidated the pharmacological mechanism of ZSYTP on POI using a network pharmacology approach and further validated our findings with molecular docking. Methods. A comprehensive strategy based on several Chinese herb databases and chemical compound databases was established to screen active compounds of ZSYTP and predict target genes. For network pharmacological analysis, network construction and gene enrichment analysis were conducted and further verified by molecular docking. Results. A total of 476 target genes of ZSYTP were obtained from 205 active compounds. 13 herbs of ZSYTP overlapped on 8 active compounds based on the compound-target-disease network (C-T network). 20 biological processes and 9 pathways were strongly connected to the targets of ZSYTP in treating POI, including negative regulation of gene expression, mRNA metabolic process, hypoxia-inducible factor 1 (HIF-1) signaling pathway, and gluconeogenesis. Finally, molecular docking was visualized. Conclusion. Intriguingly, the signal pathways and biological processes uncovered in this study implicate inflamm-aging and glucose metabolism as potential pathological mechanisms of POI. The therapeutic effect of ZSYTP could be mediated by regulating glucose metabolism and HIF-1 signal pathway. Collectively, this study sheds light on the therapeutic potential of ZSYTP on POI.

Automated summary

This study systematically elucidated the pharmacological mechanism of Zishen Yutai Pills (ZSYTP) on Premature ovarian insufficiency (POI) using a network pharmacology approach and molecular docking. The results suggest that ZSYTP may regulate inflamm-aging and glucose metabolism pathways to potentially treat POI, shedding light on its therapeutic potential in this reproductive disease.