Deciphering the Nrf2/ARE Mechanism: GanCaoXieXin Decoction Combats Oxidative Stress in Ulcerative Colitis Pathogenesis
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Background
GanCaoXieXin (GCXX) decoction, a classic prescription, has shown clinical efficacy in treating ulcerative colitis (UC). However, its mechanism remains incompletely understood.
Objective
This study aims to explore how GCXX modulates the Nrf2/ARE signaling pathway to mitigate oxidative stress (OS)-induced damage and thereby ameliorate UC.
Materials and methods
Network pharmacology and bioinformatics analyses identified key targets of GCXX in UC treatment. Ultra-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC-MS/MS) analyzed GCXX’s effective compounds. A 2.5% Dextran Sulfate Sodium Salt (DSS)-induced UC mouse model was used. Immunohistochemistry (IHC) assessed tight junction proteins. Enzyme-linked immunosorbent assay (ELISA) measured intestinal permeability and oxidative stress markers. Western blot (WB) analyzed Nrf2/ARE signaling proteins. In 800μmol/L H2O2-induced oxidative stress (OS) state HT-29 cells, cell viability, apoptosis, oxidative stress indicators, and apoptosis-related proteins were evaluated. Immunofluorescence (IF) detected Nrf2/ARE signaling axis proteins.
Results
The results of network pharmacology and bioinformatics analysis revealed that GCXX could intervene in UC by regulating OS-related pathways. GCXX contained antioxidant components like quercetin, berberine, and baicalin. In vivo , GCXX alleviated mucosal damage, reduced intestinal permeability, downregulated MDA, upregulated SOD, suppressed Keap1, and promoted tight junction and Nrf2/ARE pathway proteins. In vitro , GCXX increased cell survival, improved antioxidant capacity, reduced MDA and apoptosis in OS state cells. Immunofluorescence confirmed Nrf2/ARE pathway as crucial in GCXX’s protective effects.
Conclusions
GCXX elevates the expression level of Nrf2, HO-1 and NQO1, thus reducing entercell OS-induced damage, intestinal cell apoptosis, alleviating UC intestinal mucosal damaget.
