Quercetin Protects Mice From Autoimmune Hepatitis

Objective Massive necrosis and apoptosis of liver cells is the common feature of different kinds of liver diseases, such as viral hepatitis, alcoholic hepatitis, autoimmune hepatitis, etc. Many studies have demonstrated that tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a critical regulator of hepatocyte physiology in a variety of pathophysiologic conditions. In most cases, the apoptosis of liver cells is mediated by the TRAIL-induced expression of a variety of genes, in which the transcription factor NF-κB plays a central role. Disruption of the NF-κB or TRAIL pathway can reduce inflammation and autoimmune diseases. Consequently, we suggest some potential strategies to mediate liver disease. Quercetin, [2-(3, 4-dihydroxyphenyl)-3, 5, 7-trihydroxy-4H-1-benzopyran-4-one dehydrate], is one of the major flavonoids in certain species of plants. It has been reported that quercetin can effectively blockade the activation of NF-κB.The present study was designed to investigate the effects of quercetin on the activation of nuclear factor kappa B (NF-κB) and the expression of TRAIL in an experimental model of autoimmune hepatitis induced by Intravenous injection of Con A.Methods In this study, we examined the effect of quercetin in a mouse model of autoimmune hepatitis. Mice were treated with Concanavalin A (Con A) and were injected with quercetin half an hour later. After 2 hours of injection of Con A, the serum was obtained from mouse to assay the injury of hepatocyte. Liver injury was also assessed by HE stain. Cytokine expression was measured by real time PCR. The inhibition of NF-κB was also determined by theimmunohistochemistry in liver tissues embedded in paraffin. Results In the quercetin-treated mice, the serum levels of ALT and AST were significantly decreased. There were fewer tumor necrosis factor a (TNF-a)-induced apoptotic cells in liver cells treated with quercetin than in non-treated liver cells. Quercetin decreased the expression levels of mRNA transcripts encoding TNF-ot and NF-kBn TRAIL. No adverse consequences were showed in gross measures such as weight loss> ruffling of fm\ life spam behavior or feeding. None of pathologic changes in liver ^ lung> kidney, etc. have been found by microscopic examination, besides wildly spleen proliferation in only quercetin treated mice. Conclusions1 -, Quercetin markedly attenuated an increase of enzyme activity caused byintravenous injection of Con A;2 .. Quercetin significantly inhibited expression levels of mRNA transcriptsencoding TNF-cc;3 ^ Quercetin inhibited NF-kB as assessed by immunohistochemical andinhibited expression levels of mRNA transcripts encoding NF-kB; 4^ Quercetin significantly inhibited expression levels of mRNA transcriptsencoding TRAIL;The present study paves the basis for the further investigation of quercetin. It may be of importance to the further exploration of the potential application of this kind of flavonoids in the treatment of chronic hepatitis and hepatic fibrosis. One could also achieve better by combining quercetin with other anti-inflammation drugs. These findings may provide a new strategy for treatment of hepatitis induced by Con A through the induction of quercetin. Quercetin should, thus, be considered as a novel candidate for the therapy of liver injury.