Integration of LC-LTQ-Orbitrap-MS and Network Pharmacology to Analyze the Active Components of Sijunzi Decoction and their Mechanism of Action Against Cytotoxicity-associated Premature Ovarian Insufficiency.

Abstract

Sijunzi Decoction (SJZD) is a classical prescription in traditional Chinese medicine that enhances neuroimmune endocrine function to alleviate inflammatory aging, a key pathogenic mechanism underlying premature ovarian insufficiency (POI). However, the mechanism through which SJZD alleviates POI remains unknown. Hence, we aimed to identify the active components of SJZD and its mechanism of therapeutic action against POI. We identified compounds in SJZD using liquid chromatography-linear trap quadrupole-Orbitrap-mass spectrometry (LC-LTQ-Orbitrap-MS) and the TCMSP, HERB, Swiss, SEA, and STRING databases. We analyzed Gene Ontology (GO) terms and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using RStudio and constructed a visual network using Cytoscape. We identified 98 compounds using LC-LTQ-Orbitrap-MS, among which 29 were bioactive and screened using the databases. The screen yielded 151 predicted targets of these compounds that were associated with POI. The results of the GO and KEGG analyses showed that these compounds play key roles in cell growth, division, migration, and survival signaling pathways. Therefore, phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK), and epidermal growth factor receptor (EGFR) pathways might be closely associated with the pharmacological effects of SJZD on the pathological processes of POI. Our findings provide a scientific basis for rapidly analyzing bioactive compounds in SJZD and their pharmacological mechanisms.