Explanation of the potential mechanism of Sophora flavescens Ait and processed products treating ulcerative colitis based on the analysis method of “chemical composition characterization-target prediction”

Abstract

Processing is often used to prepare decoctions of traditional Chinese medicine (TCM) with reduced toxicity and enhanced efficacy. While Sophora flavescens Ait (SFA) is often used directly, processing with rice-washed water (RSFA) was performed in ancient times, and processing with wheat bran (WSFA) is a more modern method. Processing has been shown to enhance the anti-inflammatory and antibacterial effects of SFA, though the mechanisms underlying this change are unclear. In this study, a total of 106 active components of SFA, RSFA, and WSFA, mostly alkaloid and flavonoid derivatives, were identified using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and a total of 159 potential molecular targets in the treatment of ulcerative colitis were identified by network pharmacology. Relationships among key targets, including epidermal growth factor receptor, heat shock protein 90, SRC, and p100α, were identified through development of a protein–protein interaction network. GO enrichment indicated that peptidyl-tyrosine phosphorylation, peptidyl-tyrosine modification, and cellular response to chemical stress are important in the action of SFA against ulcerative colitis, and KEGG enrichment showed that the phosphoinositide 3-kinase-AKT signaling pathway is another key target. Molecular docking showed that the active components have strong affinities for phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha and protein kinase C alpha. In vitro cell experiments have demonstrated that five active components in SFA can exert anti-inflammatory effects by modulating IL-6 and IL-10. We found that processing results in changes in the chemical composition of SFA that influence the treatment of UC. This study provides a reference for further research into the pharmacodynamic basis for the enhanced efficacy of processed SFA in the treatment of ulcerative colitis.