Abstract
It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. Natural compounds from Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with various beneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has been shown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microglia cells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitory effects on NO production of DMC at 65 μM for 24-96 h were assessed by monitoring nitrite levels. Expression of iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.
Highlights
Intestinal mucosa acts as a barrier to protect the gut from various chemicals and foreign pathogens
Decrease in nitric oxide (NO) production by DMC was concomitant with down-regulation of inducible nitric oxide synthase (iNOS) at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls
In the immunologic inflammatory bowel disease (IBD) mouse model, iNOS, 8-nitroguanine, 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) and proliferating cell nuclear antigen (PCNA) were expressed in epithelial cells indicating nitrative and oxidative DNA damage followed by proliferation of these cells, which may contribute to IBD carcinogenesis (Ding et al, 2005)
Summary
Intestinal mucosa acts as a barrier to protect the gut from various chemicals and foreign pathogens. The expression of iNOS mRNA was significantly increased during neoplastic transformation of colonic mucosa in ulcerative colitis patients (Svec, et al, 2010). These data implicate that iNOS/NO plays a role. It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. The role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut
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