Effects of zerumbone on chronic gastritis remain unclear. The purpose of this study was to investigate the mechanism of the protective effect of zerumbone on the treatment of chronic gastritis in rats. The animal models of chronic gastritis in rats were established, and the surface damage of gastric mucosa was observed by gross anatomy; the changes of gastric mucosal tissue and surface morphology were observed by pathological sections of gastric mucosal tissues; the expressions of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor 2 (Nrf-2) proteins of gastric mucosal tissues in each group were detected by western blot analysis; the activities of superoxide dismutase (SOD) and catalase (CAT) as well as the contents of reduced glutathione (GSH) and malondialdehyde (MDA) in gastric mucosal tissues were detected by kits. The results indicated that zerumbone could significantly relieve red and swelling as well as erosion of the gastric mucosal tissues in rats with chronic gastritis; zerumbone could significantly ameliorate the loose arrangement of cells in the lamina propria of gastric mucosa, epithelial cell deformation and abscission, and inflammatory cell infiltration. The results of western blot analysis showed that compared with the model group, zerumbone could significantly upregulate the expression of HO-1 and Nrf-2 in gastric mucosal tissues. Compared with the model group, the activities of SOD and CAT as well as GSH levels in gastric mucosal tissues of rats in the zerumbone groups were obviously increased, but MDA contents were significantly decreased. Zerumbone has a protective effect on chronic gastritis in rats, which is achieved by improving the antioxidant capacity of gastric mucosal tissues through inhibiting lipid peroxidation.

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