Flavonoids from Chroogomphus rutilus attenuate DSS-induced colitis, exhibiting anti-inflammatory, antioxidant, and gut microbiota-modulating effects.

INTRODUCTION: Chroogomphus rutilus (CR) is an edible mushroom valued for its bioactive polysaccharides and flavonoids. It possesses antioxidant and anti-inflammatory properties; however, whether it can confer protection against the onset of ulcerative colitis (UC) remains unclear. METHODS: Initial network pharmacology analysis was performed to evaluate the potential influence of the flavonoid fraction of CR (CRF) on UC-related targets involved in inflammatory signaling and oxidative stress. The effects of CRF pretreatment were subsequently investigated in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Mice received oral CRF pretreatment at doses of 100 or 400 mg/kg, followed by induction of acute colitis with 3% DSS. RESULTS: CRF pretreatment suppressed colonic proinflammatory cytokine expression and preserved antioxidant defense. 16S rRNA gene sequencing revealed that CRF modulated the gut microbiota composition by suppressing potentially harmful bacteria, such as Bacteroides and Erysipelatoclostridium, and enriching beneficial genera including Bifidobacterium, Dubosiella, and Faecalibaculum. DISCUSSION: These correlative findings suggest that CRF pretreatment attenuates DSS-induced colitis, and that this attenuation is accompanied by reduced inflammation, alleviated oxidative stress, and microbiota remodeling. The data support the hypothesis that CRF acts through multi-target preventive effects, highlighting its potential as a candidate functional food ingredient for further development.