curcumin alleviates matrix metalloproteinase-3 and -9 activities during eradication of helicobacter pylori infection in cultured cells and mice姜黄素减轻矩阵metalloproteinase-3和9活动在培养细胞和根除幽门螺杆菌感染的老鼠.pdfVIP

Curcumin Alleviates Matrix Metalloproteinase-3 and -9 Activities during Eradication of Helicobacter pylori Infection in Cultured Cells and Mice 1¤ 2 1 2 2 Parag Kundu , Ronita De , Ipsita Pal , Asish K. Mukhopadhyay , Dhira Rani Saha , Snehasikta Swarnakar1* 1 Indian Institute of Chemical Biology, Kolkata, India, 2 National Institute of Cholera and Enteric Diseases, Kolkata, India Abstract Current therapy-regimens against Helicobacter pylori (Hp) infections have considerable failure rates and adverse side effects that urge the quest for an effective alternative therapy. We have shown that curcumin is capable of eradicating Hp-infection in mice. Here we examine the mechanism by which curcumin protects Hp infection in cultured cells and mice. Since, MMP-3 and -9 are inflammatory molecules associated to the pathogenesis of Hp-infection, we investigated the role of curcumin on inflammatory MMPs as well as proinflammatory molecules. Curcumin dose dependently suppressed MMP-3 and -9 expression in Hp infected human gastric epithelial (AGS) cells. Consistently, Hp-eradication by curcumin-therapy involved significant downregulation of MMP-3 and -9 activities and expression in both cytotoxic associated gene (cag)+ve and cag-ve Hp-infected mouse gastric tissues. Moreover, we demonstrate that the conventional triple therapy (TT) alleviated MMP-3 and -9 activities less efficiently than curcumin and curcumin’s action on MMPs was linked to decreased pro-inflammatory molecules and activator protein-1 activation in Hp-infected gastric tissues. Although both curcumin and TT were associated with MMP-3 and -9 downregulation during Hp-eradication, but unlike TT, curcumin enhanced peroxisome proliferator- act