Poster Topical Area: Dietary Bioactive Components
Location: Hall D
Poster Board Number: 324
Objective:It is well known that dietary intake of curcumin might produce anti-inflammatory effects in the colon. However, the metabolic fate of curcumin in the colon and the role of the colonic metabolites of curcumin in anti-inflammation remain unknown. In this study, we identified the colonic metabolites of curcumin in mice fed curcumin and determined their role in anti-inflammation in cell culture. Our results showed that the metabolism of curcumin in the gastrointestinal tract was mediated by phase I & II enzymes in the gastrointestinal epithelium as well as the action of gut microbiota.
Method: After oral administration of curcumin for 6 weeks, four major curcumin metabolites were identified in the colonic mucosa of the mice, i.e. tetrahydro-curcumin (THC), hexahydro-curcumin (HHC), octahydro-curcumin (OHC), and Ferulic acid (FA). More, importantly, the abundance of these metabolites was similar or even higher than that of curcumin in the colonic mucosa. The anti-inflammatory effects of curcumin, its metabolites and their combinations were determined in the lipopolysaccharide (LPS)-treated RAW264.7 macrophages at the concentrations equivalent to those found in the colonic mucosa of the curcumin-fed mice.
Results: The results showed that curcumin showed a dose-dependent inhibition on the production of nitric oxide (NO) induced by LPS in the macrophages, while the mixture of four metabolites did not significantly inhibited NO production. However, the combination of curcumin and the metabolites showed much stronger inhibitory effects than that of curcumin or the metabolite mixture alone. More importantly, the isobologram analysis confirmed that the enhanced anti-inflammatory effects of the combination of curcumin and the metabolites were highly synergistic. The Western blotting analysis demonstrated that the combination of curcumin and its metabolites effectively suppressed the expression of iNOS and COX-2 in LPS-treated macrophages, and these effects were stronger than that produced by curcumin or the metabolite mixture alone.
Conclusion: Our findings demonstrated the significant role of the colonic metabolites of curcumin in mediating the anti-inflammatory effects of orally administered curcumin, which provided a novel mechanism of anti-inflammatory effects of curcumin.
University of Massachusetts Amherst