Oxymatrine Prevents NF-kappa B Nuclear Translocation And Ameliorates Acute Intestinal Inflammation

Abstract

Oxymatrine is a traditional Chinese herbal product that exhibits anti-inflammatory effects in models of heart, brain and liver injury. We investigated the impact of oxymatrine in an acute model of intestinal injury and inflammation. Oxymatrine significantly decreased LPS-induced NF-kappa B-driven luciferase activity, correlating with diminished induction of Cxcl2, Tnf alpha and Il6 mRNA expression in rat IEC-6 and murine BMDC. Although oxymatrine decreased LPS-induced p65 nuclear translocation and binding to the Cxcl2 gene promoter, this effect was independent of I kappa B alpha degradation/phosphorylation. DSS-induced weight loss and histological damage were ameliorated in oxymatrine-treated C57BL/6-WT-mice. While this effect correlated with reduced colonic Il6 and Il1 beta mRNA accumulation, global NF-kappa B activity as measured in NF-kappa B-EGFP mice was unaffected. Our data demonstrate that oxymatrine reduces LPS-induced NF-kappa B nuclear translocation and activity independently of I kappa B alpha status, prevents intestinal inflammation through blockade of inflammatory signaling and ameliorates overall intestinal inflammation in vivo.