Curcumin Alleviates Matrix Metalloproteinase-3 and -9 Activities during Eradication of Helicobacter pylori Infection in Cultured Cells and Mice

Parag Kundu,Ronita De,Snehasikta Swarnakar,Ipsita Pal,Asish K Mukhopadhyay,Dhira Rani Saha,Joy Sturtevant

doi:10.1371/journal.pone.0016306

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.

Highlights

Helicobacter pylori (Hp) has been implicated in the pathogenesis of most important gastroduodenal diseases, such as gastritis, peptic ulcer, gastric carcinoma and has been defined as a Class I carcinogen [1]
Since matrix metalloproteinases (MMPs)-3 and -9 plays a pivotal role in degrading majority of gastric ECM proteins during Hp-induced pathogenesis, we investigated the effects of curcumin on the levels MMP-3 and -9 in Hp-infected cultured cells
The negative regulation of curcumin on the secretion of MMP-3 and -9 was much pronounced than the other treatments in AGS cells cocultured with SS1 as evident in casein and gelatine zymography (Figure 2)

Summary

Introduction

Helicobacter pylori (Hp) has been implicated in the pathogenesis of most important gastroduodenal diseases, such as gastritis, peptic ulcer, gastric carcinoma and has been defined as a Class I carcinogen [1]. The most preferred Hp eradication therapy (tripletherapy) employ, one proton pump inhibitor and two antibiotics [4]. Such multiple therapy regimens have not been very successful in clinical practice, since the overuse or rather misuse of antibacterial agents have resulted in the emergence of antibioticresistant strains which is the prime cause of treatment failure apart from potential side effects [4,5]. Increasing complications in the conventional triple-therapy (TT) stimulate an urgent need to develop new non-antibiotic antibacterial agents against Hp-infection that are safe, highly effective and have specific cellular targets

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Conclusion