Qili Qiangxin, a compound herbal medicine formula, alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro  

作　　者：Cai-lian Fan Wan-jun Cai Meng-nan Ye Miao Chen Yi Dai 

机构地区：[1]Department of Cardiology,the First Affiliated Hospital of Jinan University,Jinan University,Guangzhou 510632,Guangdong Province,China [2]College of Pharmacy,Jinan University,Guangzhou 510632,Guangdong Province,China

出　　处：《Journal of Integrative Medicine》2022年第4期365-375,共11页结合医学学报（英文版）

基　　金：supported by Guangdong Basic and Applied Basic Research Foundation (No. 2021A1515110055)。

摘　　要：Objective: Qili Qiangxin(QLQX), a compound herbal medicine formula, is used effectively to treat congestive heart failure in China. However, the molecular mechanisms of the cardioprotective effect are still unclear. This study explores the cardioprotective effect and mechanism of QLQX using the hypoxiareoxygenation(H/R)-induced myocardial injury model.Methods: The main chemical constituents of QLQX were analyzed using high-performance liquid chromatography-evaporative light-scattering detection. The model of H/R-induced myocardial injury in H9c2 cells was developed to simulate myocardial ischemia–reperfusion injury. Apoptosis, autophagy,and generation of reactive oxygen species(ROS) were measured to assess the protective effect of QLQX. Proteins related to autophagy, apoptosis and signalling pathways were detected using Western blotting.Results: Apoptosis, autophagy and the excessive production of ROS induced by H/R were significantly reduced after treating the H9c2 cells with QLQX. QLQX treatment at concentrations of 50 and 250 μg/mL caused significant reduction in the levels of LC3Ⅱ and p62 degradation(P < 0.05), and also suppressed the AMPK/mTOR signalling pathway. Furthermore, the AMPK inhibitor Compound C(at 0.5 μmol/L),and QLQX(250 μg/mL) significantly inhibited H/R-induced autophagy and apoptosis(P < 0.01), while AICAR(an AMPK activator, at 0.5 mmol/L) increased cardiomyocyte apoptosis and autophagy and abolished the anti-apoptotic effect of QLQX. Similar phenomena were also observed on the expressions of apoptotic and autophagic proteins, demonstrating that QLQX reduced the apoptosis and autophagy in the H/R-induced injury model via inhibiting the AMPK/mTOR pathway. Moreover, ROS scavenger,N-Acetyl-L-cysteine(NAC, at 2.5 mmol/L), significantly reduced H/R-triggered cell apoptosis and autophagy(P < 0.01). Meanwhile, NAC treatment down-regulated the ratio of phosphorylation of AMPK/AMPK(P < 0.01), which showed a similar effect to QLQX.Conclusion: QLQX plays a cardioprotective role by alleviating apop

关 键 词：Herbal medicine Qili Qiangxin formula Hypoxia–reoxygenation Reactive oxygen species Autophagy Apoptosis AMPK/mTOR pathway 

分 类 号：R285[医药卫生—中药学]