Urolithin B, a Gut Microbiota Metabolite, Protects against Myocardial Ischemia/Reperfusion Injury via p62/Keap1/Nrf2 Signaling Pathway

Publication date: Available online 26 January 2020Source: Pharmacological ResearchAuthor(s): Dechong Zheng, Zumei Liu, You Zhou, Ning Hou, Wei Yan, Yuan Qin, Qianfang Ye, XinYi Cheng, Qing Xiao, Yonglin Bao, Jiandong Luo, Xiaoqian WuAbstractIschemia/reperfusion (IR) induces additional damage during the restoration of blood flow to ischemic myocardium. Urolithin B (UB) is one of the gut metabolites of ellagitannins, a class of antioxidant polyphenols, which was found to be protective against oxidative stress in multiple organs. However, the role of UB in cardiovascular disease remains elusive. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation for 30 minutes followed by 120 minutes of reperfusion, with or without UB treatment. In vitro, the H9c2 cardiomyocytes were subjected to hypoxia (94%N2/5%CO2/1%O2) for 3 hours, followed by reoxygenation (74%N2/5%CO2/21%O2) for 3 hours (HR). UB was found to decrease myocardial infarct size and attenuate the cardiac dysfunction in the rats after IR, and protect against HR injury in H9c2 cardiomyocytes. Mechanistically, UB inhibited autophagy by activating Akt/mTOR/ULK1 pathway and protected against oxidative stress and caspase 3-dependent cell apoptosis. In particular, UB induced accumulation of p62 and its interaction with Keap1, which promoted Nrf2 nuclear translocation during HR insult. Of note, the protection of UB against superoxide production and apoptotic cell death was compromised with Nrf2...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research