Curcumin promotes degradation of inducible nitric oxide synthase and suppresses its enzyme activity in RAW 264.7 cells.

Curcumin, a natural polyphenolic compound, has been reported to possess anti-inflammatory properties. Previous works showed that curcumin decreased lipopolysaccharide (LPS)-induced iNOS up-regulation at transcription level. However, whether curcumin could regulate iNOS at the post-translational level is still unclear. In the present study, we demonstrated that curcumin promoted the degradation of iNOS which is expressed under LPS stimulation in murine macrophage-like RAW 264.7 cells. Mechanically, such degradation of iNOS protein is due to ubiquitination and proteasome-dependency since it was almost completely blocked by N-benzoyloxycarbonyl-Leu-Leu-leucinal (MG132), a specific inhibitor of proteasome. Furthermore, curcumin decreased iNOS tyrosine phosphorylation through inhibiting ERK 1/2 activation and subsequently suppressed iNOS enzyme activity. In conclusion, our research displays a new finding that curcumin can promote the ubiqitination and degradation of iNOS after LPS stimulation. Copyright Â