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Besides its antioxidant activity, resveratrol was found to have antimicrobial effects by inhibiting the growth of multiple H. pylori strains. The infection by H. pylori induces an inflammatory response with the release of various cytokines and reactive oxygen species and changes in cell proliferation. The neutrophil attractant IL-8 is one of the most crucial chemokines in the host inflammatory response to H. pylori. The upregulation of IL-8 following H. pylori infection may lead to free-radical generation, and the release of proteolytic enzymes from activated neutrophils ultimately affects mucosal integrity. Pre-treatment of H. pylori-infected MKN-45 cells with resveratrol at 75 and 100 μmol/L for 4 h significantly suppressed IL-8 secretion. Moreover, ROS production was significantly suppressed by resveratrol pre-treatment at 10-100 μmol/L for the same time.
Another peculiarity of H. pylori infection is the increased severity in patients infected by strains expressing the CagA (cytotoxin associated gene A) which are endowed with an increased inflammatory potential. It has been documented that the interaction between CagA positive H. pylori strains and host cells is associated with morphological changes that lead to dysregulation of host cell functions, thereby contributing to pathogenesis. After CagA protein injection by H. pylori into the cells, CagA interacts with various intracellular signaling molecules including enzymes like Src kinases, eventually leading to increased cell motility and the hummingbird phenomenon. Resveratrol pre-treatment (100 μmol/L) for 2 h blocked the morphological changes induced by infection with a CagA positive H. pylori strain in the MKN-45 cells.
Resveratrol may be a particularly important preventive tool in GC since H. pylori strains isolated from gastric carcinoma biopsies show an increased susceptibility to resveratrol compared with strains isolated from patients with chronic gastritis alone. The hypothesis is that one target of the antibacterial action of resveratrol may be one or more F-type ATPases, which normally protect the bacteria from low pH levels by maintaining a proton gradient across membranes. In strains isolated from patients with gastric carcinoma, such an enzyme may be underexpressed, as an adaptive response to an environment that has lost its natural acidity. Thus, the bacterial defenses are reduced and then susceptibility to resveratrol is increased, so that it saturates its targets more quickly and efficiently.
Article Produced By
Aida Zulueta, Anna Caretti, Paola Signorelli, Riccardo Ghidoni, Department of Health Sciences, San Paolo Hospital, University of Milan, 20142 Milano, Italy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588085/
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