Systematic Pharmacology-Based Strategy to Explore the Molecular Network Mechanism of Modified Taohong Siwu Decoction in the Treatment of Premature Ovarian Failure

Abstract

Objective. To explore the molecular network mechanism of modified Taohong Siwu Decoction (MTHSWD) to interfere with premature ovarian failure based on systematic pharmacological strategy. Methods. The network pharmacology strategy was used to explore the potential mechanism of MTHSWD intervention in POF, and then it was verified through animal experiments. Mouse zona pellucida 3 was used as an antigen to subcutaneously immunize BALB/c female mice to establish an immune POF model. Mice were divided into MTHSWD low-, medium-, and high-dose groups, positive control group, model group, and normal group. After 30 days of drug intervention, ovarian tissue was taken for pathological hematoxylin-eosin (HE) staining, and immunohistochemical methods were used to detect the expression of TGF-β1 and TGF-βRII and Smad2/3 protein expression in follicular wall granular cells and ovarian tissue, respectively. Results. Network pharmacology studies have shown that MTHSWD may interfere with the TGF-β signaling pathway. Animal experimental research shows that, compared with the model group, the number of ovarian mature follicles in the MTHSWD groups and the positive group was significantly increased, and the number of atresia follicles decreased. Immunohistochemistry showed that, compared with the control group, the expression of TGF-β1, TGF-βRII, and Smad2/3 in the follicular wall granulosa cells and ovarian tissues of MTHSWD groups was significantly higher than that of the model group ( $P<0.05$ ). Conclusion. MTHSWD may improve the ovarian function of POF mice by upregulating the protein expression of granulosa cells TGF-β1, TGF-βRII, and Smad2/3.