title: Curcumin alleviates matrix metalloproteinase-3 and -9 activities during eradication of Helicobacter pylori infection in cultured cells and mice.
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-activated receptor-γ and inhibitor of kappa B-α. These data indicate that curcumin-mediated healing of Hp-infection involves regulation of MMP-3 and -9 activities.
authors.affiliation: Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Parag
authors.initials: P
authors.lastname: Kundu
authors.forename: Ronita
authors.initials: R
authors.lastname: De
authors.forename: Ipsita
authors.initials: I
authors.lastname: Pal
authors.forename: Asish K
authors.initials: AK
authors.lastname: Mukhopadhyay
authors.forename: Dhira Rani
authors.initials: DR
authors.lastname: Saha
authors.forename: Snehasikta
authors.initials: S
authors.lastname: Swarnakar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016481:Helicobacter Infections / Q000188:drug therapy*; D006801:Humans; D007249:Inflammation; D018836:Inflammation Mediators; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D013270:Stomach / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D003474:Curcumin