Peimine Alleviates DSS-Induced Colitis by Modulating Gut Microbiota and Attenuating Inflammation and Oxidative Stress

Peimine (PM), a steroidal alkaloid derived from aged garlic (<i>Allium sativum</i> L.), demonstrates potent therapeutic efficacy against ulcerative colitis (UC) through multi-target mechanisms. Integrating network pharmacology and in vivo validation, we reveal that PM suppresses colitis by concurrently inhibiting PI3K-AKT, JAK-STAT, and HIF-1 signaling pathways-key drivers of inflammation and oxidative stress. In a murine model of dextran sulfate sodium (DSS)-induced UC, oral PM administration (4 mg/kg) significantly attenuated disease severity, evidenced by reduced disease activity index, restored colon length, and improved epithelial barrier integrity. PM treatment diminished pro-inflammatory cytokines TNF-α (4.2-fold) and IL-6 (3.1-fold) and oxidative damage while reshaping gut microbiota composition to enrich beneficial taxa (<i>Akkermansia muciniphila</i>, <i>Lactobacillus</i> spp.). Critically, PM rescued fecal short-chain fatty acid (SCFA) production (acetate, propionate, butyrate), directly linking microbial remodeling to mucosal healing. These findings establish PM as a novel natural compound targeting inflammation-redox-microbiota crosstalk, offering a promising pharmacological strategy for UC management.