Inhibition of nitric oxide and cytokine production by curcumin, and antioxidative phytochemical.

摘要

Curcumin, a natural occuring phytochemical extracted from turmeric ( Curcuma longa), has been shown to attenuate chemical carcinogenesis in rodents and has also been reported to possess antioxidant and anti-inflammatory properties. The mechanism of its actions still remains unknown. Previous studies have shown that curcumin can scavenge reactive oxygen intermediates (ROIs), suppress the biosynthesis of prostaglandins, (PGs), and inhibit the activation of transcription factor activator protein-1 (AP-1). The objective of my study is to evaluate the anti-inflammatory activity of curcumin and its potential for in vivo application. Nitric oxide (NO) is an important free radical produced by nitric oxide synthase (NOS) of macrophages and neutrophils during inflammation. Murine peritoneal macrophages produce large amounts of nitric oxide in response to lipopolysaccaride (LPS) via the activation of inducible nitric oxide synthase (iNOS or NOS II). According to our experiments, curcumin and two other natural compounds, (-)epicatechin-3-gallate (EGCG) from green tea and carnosol from rosemary, decreased the production of nitric oxide by peritoneal exudated cells in a dose-dependent way without affecting the viability of cells. In the enzymatic activity assay, all these compounds had no influence on activity of their effective concentrations. Curcumin and EGCG attenuated the mRNA expression of iNOS of murine PEC in a concentration-dependent manner. Thus, the inhibition of nitric oxide production is at least partly due to the suppression of the transcription of the NOS gene. Since nitric oxide has been reported to play important roles in inflammatory reactions, the decrease in nitric oxide release must contribute to the anti-inflammatory properties of these agents. The effect of curcumin on the transcription of other mediators including COX-2, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta) was also evaluated. Our results suggest curcumin has a broad effect on the mRNA expression of a variety of inflammatory mediators. Some anti-inflammatory reagents also have broad effects on mediators produced during inflammation. Endotoxemia, of mice induced by LPS injection can express many inflammatory mediators including iNOS and cytokines. In my experiments, gavage feeding of 10 muM curcumin before LPS challenge could efficiently suppress the gene expression of NOS and cytokines in liver and spleen. In conclusion, curcumin is a potent natural compound in inhibiting the nitric oxide production and gene expression of inflammatory mediators. Its action can be delivered in vivo through an appropriate feeding scheme. Because the lower toxicity of curcumin, it might be a suitable compound that can be used for clinical applications.