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

## TL;DR

A composite of ginseng, salvia root, and notoginseng helps treat colitis by reducing inflammation, boosting antioxidants, and improving gut health in mice.

## Contribution

The study reveals a multi-target mechanism of a natural composite in treating colitis through Nrf2 activation and gut microbiota modulation.

## Key findings

- GSNS reduced inflammation and oxidative stress via the Nrf2/HO-1 pathway in colitis mice.
- GSNS repaired intestinal barriers by upregulating Occludin and restoring tight junctions.
- GSNS improved gut microbiota by increasing Prevotellaceae and reducing Escherichia-Shigella.

## Abstract

Current treatments for ulcerative colitis (UC) often fail to adequately address its multifactorial pathogenesis, which involves 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 mouse model of colitis induced by dextran sulfate sodium (DSS). Based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technology, 25 major bioactive components were identified. Following the induction of colitis with 3.5% DSS in C57BL/6J mice, the animals were treated with the 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 a barrier integrity test. Combined data from Western blot, qPCR, immunohistochemistry, electron microscopy, and 16S rRNA sequencing indicate that the therapeutic effect of the GSNS against colitis is attributable to its dual role in dampening pro-inflammatory cytokines and potentiating antioxidant defenses via the Nrf2/HO-1 signaling pathway. It also upregulated Occludin expression, repaired tight junctions, and was associated with beneficial alterations in the gut microbiota, as evidenced by increased Prevotellaceae and suppressing Escherichia-Shigella. These findings demonstrated that the 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 DSS-induced colitis treatment.