Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOS/NO-Regulated Oxidative Stress

• Published in: Oxidative medicine and cellular longevity 2018-01, Vol.2018 (2018), p.1-15
• Main Authors: Tang, Qi-Zhu, Liao, Hai-Han, Yuan, Yuan, Liu, Chen, Duan, Ming-Xia, Xiao, Yang, Wu, Qing-Qing, Yang, Zheng, Meng, Yan-yan
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Cell culture; Cell cycle; Cell Line; Coronary vessels; Disease Models, Animal; Echocardiography; Endoplasmic reticulum; Heart attacks; Hemodynamics - drug effects; Immunoglobulins; Immunohistochemistry; In Situ Nick-End Labeling; Inflammation; Infrared imaging systems; Iridoid Glucosides - therapeutic use; Kinases; Laboratory animals; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction - drug therapy; Myocardial Infarction - metabolism; Myocardium - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Neurosciences; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide Synthase Type I - metabolism; Nitrogen Oxides - metabolism; Oxidative stress; Oxidative Stress - drug effects; Physiology; Proteins; Rats; Reactive Oxygen Species - metabolism; Rodents; Signal transduction; Surgery; Thioredoxins - metabolism; Veins & arteries; Ventricular Remodeling - drug effects
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2018/4327901

Whether aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of aucubin on cardiac remodeling. Taken together, aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.