Activation of the Nrf2 Signaling Pathway by a Ginseng-Salvia-Notoginseng Composite Alleviates Ulcerative Colitis via Restoring Gut Microbiota and Intestinal Barrier

Current treatments for ulcerative colitis (UC) often fail to adequately address its multifactorial pathogenesis, involving oxidative stress, barrier dysfunction, and gut microbiota dysbiosis. This study evaluated the therapeutic potential and multi-targeting mechanism of a ginseng, salvia root, and notoginseng oral solution (GSNS) in a DSS-induced mouse colitis model. Based on HPLC-MS/MS technology, 24 major bioactive components were identified. Following the induction of UC with 3.5% dextran sulfate sodium (DSS) in C57BL/6J mice, the animals were treated with GSNS (40, 80, or 160 mg/kg/day) or 5-Amino Salicylic Acid (5-ASA). The therapeutic efficacy was assessed via disease activity, histopathological staining, cytokines, and oxidative stress analysis, and barrier integrity test. Combined data from Western blot, qPCR, immunohistochemistry, electron microscopy, and 16S rRNA sequencing indicate that the therapeutic effect of GSNS against colitis is attributable to its dual role in dampening pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and potentiating antioxidant defenses via the Nrf2/HO-1 signaling pathway. It also upregulated Occludin expression, repaired tight junctions, and beneficially reshaped the gut microbiota by increasing Prevotellaceae and suppressing Escherichia-Shigella. These findings demonstrated that GSNS exerts a multi-target effect against colitis by synergistically enhancing antioxidant defense, repairing the intestinal barrier, and modulating microbial ecology, supporting its potential as a promising natural compound-based candidate for UC treatment.