Shengjiang San modification promotes colonic mucosal repair in ulcerative colitis rats by inhibiting lauric acid-Shigella synergistic damage via PKC signaling pathway.

OBJECTIVES: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease. Recent research has focused on microbial dysbiosis within the gut environment. Although Shengjiang San modification ameliorates inflammation via activation of the PKC signaling pathway, the specific molecular mechanisms underlying its anti-inflammatory effects remain unclear. This study aimed to systematically investigate the anti-inflammatory mechanisms of Shengjiang San modification. METHODS: UC models were established in 50 male SD rats using Dextran Sulfate Sodium Salt (DSS). Rats were divided into model group, mesalazine group, and Shengjiang San modification high/mid/low-dose groups. After 14 days of intervention, samples were collected. General condition, gross colon morphology, and histopathological changes were observed. Untargeted metabolomics was used to detect serum metabolites, 16S rRNA sequencing was performed to analyze gut microbiota, and combined multi-omics analysis was conducted. RESULTS: Shengjiang San modification significantly improved colonic pathological injury and restored body weight. Metabolomics identified 18 aberrant metabolites, with 16 returning to near-normal levels after treatment, primarily involving the protein kinase C (PKC) signaling pathway. Gut microbiota analysis revealed decreased pathogenic bacteria and significantly increased beneficial bacteria. Notably, the lauric acid-Shigella correlation was disrupted. Compared to the control group, the high-dose group showed superior efficacy in restoring the Firmicutes/Bacteroidetes (F/B) ratio. CONCLUSIONS: Shengjiang San modification exerts anti-inflammatory effects and promotes colonic mucosal repair in UC rats by blocking lauric acid-Shigella synergistic damage via the PKC signaling pathway. The high-dose formulation demonstrated optimal therapeutic efficacy.