Quercetin Improves Mitochondrial Function and Inflammation in HO-Induced Oxidative Stress Damage in the Gastric Mucosal Epithelial Cell by Regulating the PI3K/AKT Signaling Pathway.

Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, the therapeutic strategy of which it is limited due to its complex pathogenesis. Oxidative stress-induced damage in gastric mucosal epithelial cells is related to the pathogenesis and development of FD. Quercetin (Que) is one of the active ingredients of Zhishi that showed antioxidant, antiapoptotic, and anti-inflammatory effects. The aim of this study is to investigate the effect of Que on oxidative stress-induced gastric mucosal epithelial cells damage and its underlying molecular mechanism. The gastric mucosal epithelial cell line GES-1 was treated with 200 M of HO to construct an oxidative stress-induced damage model. The HO cells were then administrated with different concentrations of Que. The results indicated that high concentration of Que (100 M) showed cytotoxicity in HO-induced GES-1 cells. However, appropriate concentration of Que (25 and 50 M) alleviated the oxidative stress damage induced by HO, as demonstrated by the increase of proliferation, decrease of ROS generation, apoptosis, inflammation, and alleviation of mitochondrial function and cell barrier. In addition, Que increased the activation of phosphorylation of PI3K and AKT decreased by HO. To investigate whether Que alleviated the oxidative stress damage in GES-1 cells by the PI3K/AKT signaling pathway, the GES-1 cells were treated with Que (25 M) combined with and without LY294002, the PI3K inhibitor. The results showed that LY294002 suppressed the alleviation effect on Que in HO-induced GES-1 cells. In conclusion, the current study demonstrates that Que alleviates oxidative stress damage in GES-1 cells by improving mitochondrial function and mucosal barrier and suppressing inflammation through regulating the PI3K/AKT signaling pathway, indicating the potential therapeutic effects of Que on FD.