Anti-inflammatory properties of uvaol on DSS-induced colitis and LPS-stimulated macrophages

BACKGROUND: L., we did a phytochemistry study and investigated anti-Inflammatory effects of compounds and explored the underlying mechanisms. METHODS: L. leaf and detected the most effective compound by NO inhibition assay. We investigated anti-Inflammatory effects on dextran sulfate sodium (DSS)-induced colitis mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The disease activity index was determined by scores of body weight loss, diarrhea and rectal bleeding; histological damage was analyzed by H&E staining; macrophages change in the colon were analyzed by immunohistochemistry (IHC); myeloperoxidase activity was measured by myeloperoxidase assay kits; levels of proinflammatory cytokines were determined by qPCR and ELISA; protein production such as COX-2, iNOS, STAT3 and ERK1/2 were determined by western blotting. RESULTS: L. leaf and found uvaol has excellent potential of inhibiting NO production. We further found uvaol could attenuate disease activity index (DAI), colon shortening, colon injury, and colonic myeloperoxidase activity in DSS-induced colitis mice. Moreover, uvaol significantly reduces mRNA expression and production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1) and infiltration of macrophages in colonic tissues of colitis mice. Studies on LPS challenged murine macrophage RAW246.7 cells also revealed that uvaol reduces mRNA expression and production of pro-inflammatory cytokines and mediators. Mechanically, uvaol inhibits the pro-inflammatory ERK/STAT3 axis in both inflamed colonic tissues and macrophages. CONCLUSIONS: leaf contains uvaol and uvaol has potent anti-inflammatory effects on DSS-induced experimental colitis and LPS-stimulated RAW264.7 macrophage cells. These results suggest uvaol is a prospective anti-inflammatory agent for colonic inflammation.