NETWORK PHARMACOLOGY ANALYSIS OF YI-SHEN-GU-TAI-KE-LI FOR RECURRENT SPONTANEOUS ABORTION IN FEMALE FITNESS AND ATHLETIC POPULATIONS

Abstract

Background: Yi-Shen-Gu-Tai-Ke-Li (YSGTKL), a renowned traditional herbal formula, has demonstrated clinical efficacy in addressing recurrent spontaneous abortion (RSA). Despite its widespread utilization in China, the current body of evidence regarding the effectiveness of its herbal components remains insufficient, and the underlying mechanisms of action remain enigmatic. This study endeavors to unravel the mechanisms responsible for the therapeutic effectiveness of YSGTKL in treating RSA, particularly within the context of female fitness and athletic populations.

Methods: YSGTKL comprises various herbal plants, selected based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Specific drug targets associated with RSA were meticulously identified and corroborated using multiple reputable sources, including DrugBank, GeneCards, and Online Mendelian Inheritance in Man. The GEO database was leveraged to pinpoint differentially expressed genes (DEGs) relevant to RSA within female fitness and athletic populations. Subsequently, a comprehensive drug-compound-gene-disease network was meticulously constructed and visualized using Cytoscape software. Functional insights were gleaned through Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Within this network, a subset of hub genes was discerned through a protein-protein interaction (PPI) network analysis, specifically tailored to female fitness and athletic populations. To validate key active ingredients and core targets, molecular docking analyses were meticulously performed, taking into account the unique physiological aspects of female athletes and fitness enthusiasts.

Results: A total of 195 active compounds were extracted from the 10 herbs constituting YSGTKL. Additionally, 8,905 common targets associated with RSA were identified from multiple comprehensive databases, with a specific focus on their relevance to female fitness and athletic populations. Subsequently, 432 DEGs were identified through the analysis of GEO datasets within this unique demographic, with 13 overlapping genes extracted from the integrated datasets. The resultant drug-compound-gene-disease network comprised 10 herbs, 123 compounds, and 13 pivotal targets, all tailored to the specific context of female fitness and athletic populations. These identified genes exhibited enrichment in several disease-related signaling pathways pertinent to this demographic. Notably, GF2, linked to MET, IGFBP3, and ERBB3, emerged as the hub genes in the PPI network within the context of female athletes and fitness enthusiasts. Molecular docking analyses were conducted to investigate the interaction between quercetin and IGF2, considering the unique physiological characteristics of this demographic. Importantly, downregulation of IGF2 was observed in villus samples from RSA patients within female fitness and athletic populations compared to normal pregnant women. Furthermore, it was found that quercetin promoted trophoblast cell proliferation, migration, and invasion while concurrently inhibiting IGF2 expression, highlighting its potential relevance for this demographic.

Conclusion: This study showcases the utility of network pharmacology in elucidating the effective compounds and mechanisms of action underlying the therapeutic efficacy of the YSGTKL formula in the treatment of RSA, particularly within the unique context of female fitness and athletic populations.