Hyperoside Alleviates Helicobacter pylori-Induced Gastric Epithelial Cell Injury by Regulating Nrf2/HO-1 Signaling.

Abstract

Infection with Helicobacter pylori is the major causative factor of chronic gastritis, peptic ulcer, gastric cancer, and other diseases. Gastric mucosal epithelial injury characterized by abnormal apoptosis, oxidative stress, and inflammation is a crucial mechanism of H. pylori infection. Hyperoside (HYP) is a flavonol glycoside derived from many herbal plants, which exhibits potent anti-apoptotic, antioxidant, and anti-inflammatory properties. Our research explored whether it exerts protective effects on H. pylori-infected human gastric epithelial cells. GES-1 cells were first treated for 24 h with HYP (0, 10, 20, 40, 80, 100, or 120 μM) to determine the cytotoxicity of HYP. Subsequently, GES-1 cells were pre-treated for 4 h with HYP (80 μM), followed by exposure to H. pylori for 24 h. CCK-8 assay, flow cytometry assay, ELISA, RT-qPCR, DCFH-DA staining, the commercial assay kits, immunofluorescence staining, and western blotting were used to assess cell viability, cell apoptosis, pro-inflammatory cytokine levels, oxidative stress marker levels, and Nrf2/HO-1 signaling-related molecule levels. The Nrf2 inhibitor ML385 was employed to verify the beneficial role of Nrf2 activation in HYP-mediated GES-1 cell injury induced by H. pylori. The results showed that HYP pre-treatment reversed H. pylori-induced cell apoptosis, inflammation, and oxidative stress in GES-1 cells. Furthermore, HYP downregulated Nrf2, HO-1, and NQO1 protein levels in H. pylori-infected GES-1 cells. ML385 overturned the protective effects of HYP against H. pylori-induced GES-1 cell apoptosis, inflammation, and oxidative stress. In conclusion, HYP protects gastric epithelial cells against H. pylori-induced cell injury by activating the Nrf2/HO-1 pathway.