Abstract
BACKGROUND: Gegen Qinlian Decoction (GQD), a traditional Chinese medicine formula, has shown significant therapeutic potential for colitis. However, the specific mechanisms by which GQD exerts its effects remain poorly understood, limiting its application in UC treatment. PURPOSE: In this study, we utilized a dextran sodium sulfate-induced colitis model in mice to evaluate the efficacy of GQD and to elucidate its underlying mechanisms. METHODS: Network pharmacology was employed to explore the potential targets and signaling pathways of GQD, which were subsequently validated using Western blot. The effects of GQD on gut barrier integrity, inflammation, and oxidative damage were assessed through immunofluorescence, immunohistochemistry, and ELISA. Additionally, 16S rRNA high-throughput sequencing was conducted to examine alterations in the gut microbiota composition. RESULTS: The results demonstrated that GQD alleviated the colitis symptoms in mice, as evidenced by an increase in goblet cell numbers, upregulation of ZO-1, MUC-2, and Occludin expression, and a decrease in apoptosis in intestinal epithelial cells. GQD effectively suppressed the expression of pro-inflammatory and oxidative mediators, including interleukin-6, tumor necrosis factor-α, interleukin-1β, nitric oxide, malondialdehyde, and myeloperoxidase, with inhibition rates ranging from 47% to 66%. According to the results from Western blot, the phosphorylation levels of p53, Akt, STAT3, and MAPK inflammatory signaling pathway-related proteins (p38, ERK, and JNK) were significantly inhibited with GQD treatment. Furthermore, GQD re-regulated composition of gut microbiota, including inhibiting the harmful bacteria (Proteobacteria, Bacteroides, and Romboutsia) enrichment and restoring the probiotics (Lactobacillus and Allobaculum). The correlation analysis revealed that the abundances of gut microbiota were closely related to the key protein expression in colon. CONCLUSION: This study revealed GQD can alleviate colitis by attenuating inflammation, restoring intestinal mucosal barrier and modulating gut microbiota.