Quercetin Improves Mitochondrial Function and Inflammation in H2O2-Induced Oxidative Stress Damage in the Gastric Mucosal Epithelial Cell by Regulating the PI3K/AKT Signaling Pathway.

Xueting Yao,Wanyu Mao,Yingbing Mei,Yoke Keong Yong

doi:10.1155/2021/1386078

Abstract

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 μM of H2O2 to construct an oxidative stress-induced damage model. The H2O2 cells were then administrated with different concentrations of Que. The results indicated that high concentration of Que (100 μM) showed cytotoxicity in H2O2-induced GES-1 cells. However, appropriate concentration of Que (25 and 50 μM) alleviated the oxidative stress damage induced by H2O2, 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 H2O2. 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 μM) combined with and without LY294002, the PI3K inhibitor. The results showed that LY294002 suppressed the alleviation effect on Que in H2O2-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.

Highlights

Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, comprising three subtypes based on pathophysiology and aetiology: epigastric pain syndrome, postprandial distress syndrome, and a subtype with overlapping epigastric pain syndrome and postprandial distress syndrome [1]. e prevalence of FD varies widely worldwide
When the confluence reached 80–90%, the cells were treated for 24 h with different concentration of quercetin (Que, 0, 12.5, 25, 50, and 100 μM), followed by addition 200 μM H2O2 treatment. e cells in control group were treated with normal medium. e cells in the model group were only treated with 200 μM H2O2 [20]. e cell proliferation, apoptosis, inflammation, mitochondrial function, barrier, and the activity of phosphatidylinositol-3 kinase (PI3K)/AKT pathway were evaluated
When the confluence reached 80–90%, the cells were treated for 24 h with different concentration of quercetin (Que, 0, 12.5, 25, 50, and 100 μM) [20], followed by addition 200 μM H2O2 treatment. e cells were treated with addition of 10 μl of cell counting kit-8 (CCK-8) solution (Solarbio) and cultured for 4 h. en, the cells were subjected to a microplate reader (Allsheng) to detect the optical density of cell at 450 nm

Summary

Introduction

Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, comprising three subtypes based on pathophysiology and aetiology: epigastric pain syndrome, postprandial distress syndrome, and a subtype with overlapping epigastric pain syndrome and postprandial distress syndrome [1]. e prevalence of FD varies widely worldwide. Que alleviates H2O2-induced oxidative stress, apoptosis, and inflammatory in GES-1 cells. (d) Western blot was performed to detect the apoptosis-related proteins Bax, Bcl-2, and cleaved caspase 3 expression in GES-1 cells.

Results

Conclusion