Yao Xueting, Mei Yingbing, Mao Wanyu
Department of Traditional Chinese Medicine, Wuhan Third Hospital, Wuhan, China.
Department of Geriatrics, Hubei Provincial Hospital of Traditional Chinese Medicine, Hubei, China.
Evid Based Complement Alternat Med. 2021 Nov 27;2021:1386078. doi: 10.1155/2021/1386078. eCollection 2021.
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.
功能性消化不良（FD）是最常见的功能性胃肠疾病之一，由于其发病机制复杂，其治疗策略有限。氧化应激诱导的胃黏膜上皮细胞损伤与FD的发病机制和发展有关。槲皮素（Que）是枳实的活性成分之一，具有抗氧化、抗凋亡和抗炎作用。本研究旨在探讨Que对氧化应激诱导的胃黏膜上皮细胞损伤的影响及其潜在分子机制。用200μM的HO处理胃黏膜上皮细胞系GES-1，构建氧化应激诱导的损伤模型。然后用不同浓度的Que处理HO细胞。结果表明，高浓度的Que（100μM）在HO诱导的GES-1细胞中显示出细胞毒性。然而，适当浓度的Que（25和50μM）减轻了HO诱导的氧化应激损伤，表现为增殖增加、ROS生成减少、凋亡减少、炎症减轻以及线粒体功能和细胞屏障的改善。此外，Que增加了被HO降低的PI3K和AKT磷酸化的激活。为了研究Que是否通过PI3K/AKT信号通路减轻GES-1细胞中的氧化应激损伤，将GES-1细胞用Que（25μM）联合或不联合PI3K抑制剂LY294002处理。结果表明，LY294002抑制了Que对HO诱导的GES-1细胞的减轻作用。总之，本研究表明，Que通过改善线粒体功能和黏膜屏障以及通过调节PI3K/AKT信号通路抑制炎症来减轻GES-1细胞中的氧化应激损伤，表明Que对FD具有潜在的治疗作用。
