Exploration of the Underlying Mechanism of Jiawei Shixiao San in the Treatment of Endometriosis Using Network Pharmacology and Experimental Verification

Aim Shixiao San, composed of Pollen Typha and Faeces Trogopterori, is a traditional Chinese medicine used for the the treatment of endometriosis. Jiawei Shixiao San is a modified formula derived from Shixiao San, adding with Sanguis Draconis, Lignum Sappan, Fritillariae thunbergii bulbus, Semen Coicis, and Radix Notoginseng. The purpose of this study was to elucidate the mechanism of Jiawei Shixiao San in combating endometriosis at a systemic level through network pharmacology and experimental verification. Methods The targets of Jiawei Shixiao San and endometriosis were retrieved from multiple databases. An herbs-compounds-genes network and a protein-protein interaction network were constructed to analyze target interactions. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted using the DAVID database. Finally, CCK-8 assays and flow cytometry analyses were performed to evaluate the anti-endometriosis effects of the active compounds. Results A total of 157 common targets associated with herbs and endometriosis were identified for analysis. The key targets included AKT1, IL-6, TNF, ESR1, TP53, VEGFA, EGFR, and SRC. The potential active compounds identified were quercetin, pelargonidin, isorhamnetin, and kaempferol. Enrichment analysis suggested that Jiawei Shixiao San may treat endometriosis through the PI3K-Akt signaling pathway, resistance to EGFR tyrosine kinase inhibitors, endocrine resistance, and the AGE-RAGE signaling pathway. Further experimental validation demonstrated that kaempferol could inhibit the proliferation of endometrial stromal cells and induce apoptosis. Conclusion In summary, we conducted network pharmacology analysis combined with experimental verification to provide compelling evidence that Jiawei Shixiao San may treat endometriosis by regulating cell proliferation and apoptosis, as well as by modifying inflammation-related genes and signaling pathways.