Deciphering the Nrf2/ARE Mechanism: GanCaoXieXin Decoction Combats Oxidative Stress in Ulcerative Colitis Pathogenesis
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
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.
