Attenuation Of The Expression Of Cyclooxygenase-2 In Small Intestinal Mucosa By Berberine Hydrochloride During Acute Endotoxemia And Related Signaling Pathways Investigation

Bacterial endotoxin plays an important role in the formation of regional intestinal inflammation such as inflammatory bowel diseases (IBD), necrotizing enterocolitis (NEC), etc, as well as the formation of intestinal injury from systemic inflammation. Endotoxin directly triggers immune and inflammatory response, namely, it induces the release of cytokines including nitric oxide (NO), tumor necrosis factor alpha (TNFa), interleukin (IL-1,6,8) and production of mediators such as cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2). These stimuli may exacerbate intestinal mucosal impairment with the evidence of intestinal mucosal necrosis, fall off and intestinal epithelial cell apoptosis. In the context of breakdown of intestinal barrier, bacteria (Gram positive /negative bacteria and anaerobe) in the intestine and their lysates such as endotoxin an exotoxin go into blood circulation resulting in formation of systemic infection that, in turn, compromises intestinal mucosal barrier. The intestinal tract is one of the biggest immune organs involved in immune and inflammatory reaction. Blockade of deleterious effects of endotoxin plays a key role in maintain the intestinal mucosal integrity. Abnormally high levels of cyclooxygenase-2 and PGE2 exert similar effects like lipopolysaccharide. There is evidence that intestinal epithelial cells may produce numerous cyclooxygenase-2 in response to bacterial endotoxin stimulation. Therefore, down-regulation of cyclooxygenase-2 expression in small intestinal mucosa will be a good strategy to protect intestinal mucosal barrier during acute endotoxemia.Berberine hydrochloride is one of the constituents of herbal drugs such as Huanglian, Hydrastis Canadensis and Berberis aquifolium. In clinic, Hydrochloride berberine has been used to treat various acute and chronic gastroenteritis, bacterial-associated diarrhea and cancer for years. Many experiments have demonstrated that this botanic alkaloid can effectively attenuate side effects of LPS on intestinal mucosal structure including mucosal edema, necrosis, fall off and cell apoptosis and inhibit the biosynthesis and release of pro-inflammatory cytokines and mediators, while increase the production of anti-inflammatory cytokines.We investigate alteration of COX-2 expression in distal ileal mucosa in a rat model of acute endotoxemia and clarify the roles of p38 and PPAR gamma signaling pathways in COX-2 induction. We provide the theory basis for the usage of berberine hydrochloride in clinical practice.