Gegen Qinlian Decoction acts on colorectal cancer by regulating the gut microbiota and participating in signaling pathways such as PI3K-Akt

Abstract Background The etiology of colorectal cancer(CRC) is complex, and the intestinal flora plays a crucial role in its occurrence and development. Gegen Qinlian Decoction can regulate the intestinal flora and may be effective for CRC, but there are few studies on the specific mechanisms involved. Methods Chemical components of four herbs in GQD were collected from TCMSP and BATMAN-TCM databases, with targets predicted by SwissTargetPrediction. CRC and IF related targets from Genecards, OMIM, TTD were used to find intersections. A PPI network of common targets was constructed via STRING and a “TCM-component-target- disease- flora” network established. CytoHubba in cytoscape 3.10.3 screened HUB genes. David database was used for KEGG and GO enrichment to predict GQD-related pathways in treating CRC through IF regulation, and a “TCM-component- disease- flora- target-pathway” network was drawn. Online CB-Dock2 database and molecular blind docking verified binding of high-degree active components to Hub genes. Results A total of 73 active components in GQD were collected, with 598 potential action targets. There were 26 common targets with IF and CRC. Nine core targets, TNF, IL6, PTGS2, STAT3, ESR1, MTOR, PPARG, IL2, and CCND1, were obtained through Hub gene screening. KEGG analysis indicated that the mechanism might be related to signaling pathways such as the cancer signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. Molecular docking demonstrated that the main active components of GQD could bind well to the Hub gene targets. Conclusion GQD might treat CRC by regulating IF to activate core targets such as MTOR and PTGS2 and participate in signaling pathways such as PI3K-Akt. In this study, we verified that "multi-component, multi-target, and multi-pathway" mechanism of GQD in treating CRC.