Demethoxycurcumin from Curcuma longa Rhizome Suppresses iNOS Induction in an in vitro Inflamed Human Intestinal Mucosa Model

Background: It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integralrole during intestinal inflammation, an important factor for colon cancer development. Natural compoundsfrom Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with variousbeneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has beenshown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microgliacells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinalmucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NOproduction of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitoryeffects on NO production of DMC at 65 μM for 24-96 h were assessed by monitoring nitrite levels. Expressionof iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in ourinflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS atmRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanismof action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest thatDMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.