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.
ABSTRACT
BACKGROUND: In recent years, many clinical studies have suggested that various Chinese patent medicines have the potential to treat functional dyspepsia (FD). This study aims to conduct a systematic review and Bayesian network meta-analysis to evaluate the effectiveness of different Chinese patent medicines for FD. METHODS: A comprehensive retrieval method will be executed in the following databases: PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), VIP Database, and Wanfang Database. Clinical randomized controlled trials (RCTs) of 9 Chinese patent medicines for FD are searched, and the retrieval time is from inception to October 2021. Three reviewers will screen the RCTs that meet the inclusion criteria and extract the data independently. The outcomes include total clinical efficiency, cure rate, recurrence rate, symptom score, and adverse events. Cochrane risk-of-bias tool will be carried to assess RCTs quality. The "gemtc" package and "rjags" package in R software will be used to manage data within the Bayesian framework. RESULTS: The results can provide relatively objective evidence to evaluate the effectiveness of these 9 Chinese patent medicines in treating FD, which may help clinicians to develop a more effective and safer treatment plan. CONCLUSION: This study aims to provide new options for Chinese patent medicine treatment of FD in terms of its efficacy and safety.
