Exploring the Mechanism of Shenling Baizhu San in Mitigating Chemotherapy-Induced Intestinal Mucositis Based on Network Pharmacology and Multi-Omics Analysis.

Abstract

INTRODUCTION: This study aimed to predict the potential mechanism of Shenling Baizhu San (SBS) against Chemotherapy-induced Intestinal Mucositis (CIM) using an integrated approach combining network pharmacology, molecular docking, and molecular dynamics simulation, with its pharmacological effects and underlying mechanisms validated experimentally. METHODS: To evaluate the therapeutic effect of SBS on CIM, this study established a CIM rat model using 5-Fluorouracil (5-FU). Subsequently, we conducted a comprehensive evaluation of the model through general observation, histopathological evaluation, ELISA, immunohistochemistry, and immunofluorescence. Based on network pharmacology predictions, we validated the effect of SBS on PI3K-Akt pathway proteins by immunohistochemical staining of colon tissues. In addition, we explored the mechanism of SBS using 16S rDNA sequencing and quantitative analysis of short-chain fatty acids in feces. RESULTS: SBS significantly mitigated CIM induced by 5-FU in rats. Network pharmacology analysis revealed that quercetin and kaempferol are the primary active components of SBS. These compounds exert their effects by acting on core targets such as ESR1, HSP90AA1, and GSK3B, and modulating pathways including PI3K-Akt. Immunohistochemical staining confirmed SBS's inhibitory effect on PI3K and Akt. 16S rDNA sequencing analysis showed that SBS intervention significantly increased the richness and α-diversity of gut microbiota. Quantitative analysis of SCFAs showed that SBS significantly increased the content of acetic, propanoic, butanoic, isobutyric, valeric, isovaleric, and hexanoic acids. DISCUSSION: The integration of network pharmacology and experimental validation demonstrates that SBS primarily exerts its therapeutic effects against CIM by modulating the PI3K-Akt pathway. Analyses of gut microbiota and metabolism revealed that SBS reduces gut microbiota imbalance and increases SCFA concentrations, which, in turn, aid the recovery of intestinal mucosa damaged by injury. CONCLUSION: Our findings indicate that SBS is a multi-component agent that acts against CIM by modulating the PI3K-Akt pathway, attenuating gut dysbiosis, and elevating SCFA concentrations. These findings provide a novel mechanistic framework and translational strategy for its clinical application.

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