Network Pharmacology-based to Investigate Pharmacological Mechanisms of Active Ingredients in Gegen Qinlian Pill to Ameliorate Irinotecan-induced Diarrhea

Abstract Background: The application of natural extracts or compounds derived from Chinese medicine is deemed to a promising strategy to prevent irinotecan (CPT-11)-induced gut toxicity. Based on the protective activity of Gegen Qinlian decoction in our previous study, we speculated that Gegen Qinlian Pill (GQP) would exhibit similar therapeutic effects. However, the effective material basis and the potential mechanisms underlying the effect of GQP in the treatment of diarrhea induced by CPT-11 have not been fully elucidated. Herein, we primarily investigated amelioration effect of GQP on the CPT-11 induced gut toxicity, and further explore its anti-diarrhea mechanism.Methods: Firstly, the protective effect of GQP towards alleviating diarrhea in mice following CPT-11 administration was investigated. Furthermore, the effective ingredients of GQP in serum sample of mice by HPLC-Q-TOF-MS analysis was obtained. Next, based on these active components, an interaction network linking “compound-target-pathway” was established. Finally, a predicted mechanism within vivo validation of GQP based on Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were obtained. Results: A total of 19 chemical compounds derived from the GQP were identified in its serum sample. Then, an interaction network linking “compound-target-pathway” was established to illuminate the interaction between these components absorbed into serum and their targets for diarrhea. GQP exerted a curative effect on diarrhea and diarrhea-related diseases by targeting different targets, regulating inflammation, oxidative stress, and proliferation processes. Conclusion: Taken together, this study provides a novel and scientific strategy to discover the potential effective constituents of herbs or herbal formula, and elucidated basic pharmacological effects and underlying mechanisms of GQP in the treatment of CPT-11 induced gut toxicity.