Urolithin A alleviates myocardial ischemia/reperfusion injury via PI3K/Akt pathway

Lu Tang; Yingli Mo; Yunpeng Li; Yongkang Zhong; Shangfei He; Ya Zhang; Ying Tang; Shanshan Fu; Xianbao Wang; Aihua Chen

doi:10.1016/j.bbrc.2017.03.119

Urolithin A alleviates myocardial ischemia/reperfusion injury via PI3K/Akt pathway

Biochem Biophys Res Commun. 2017 May 6;486(3):774-780. doi: 10.1016/j.bbrc.2017.03.119. Epub 2017 Mar 23.

Authors

Lu Tang¹, Yingli Mo², Yunpeng Li³, Yongkang Zhong³, Shangfei He³, Ya Zhang³, Ying Tang³, Shanshan Fu³, Xianbao Wang³, Aihua Chen⁴

Affiliations

¹ Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Gongye Road, Guangzhou 510280, China; Department of Cardiology, Yiyang Central Hospital, Kangfu Road 118, Yiyang, Hunan 413000, China.
² Department of Internal Medicine, Yiyang Medical College, Yingbin Road 516, Yiyang, Hunan 413000, China; Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
³ Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Gongye Road, Guangzhou 510280, China.
⁴ Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Gongye Road, Guangzhou 510280, China. Electronic address: aihuachenzjphd@hotmail.com.

PMID: 28343995
DOI: 10.1016/j.bbrc.2017.03.119

Abstract

Ischemia/reperfusion (I/R) induces additional damage to the restoration of blood flow to ischemic myocardium. This study examined the effects of urolithin A (UA) on myocardial injury of ischemia/reperfusion in vivo and vitro and explored its underlying mechanisms. Mice were subjected to myocardial ischemia followed by reperfusion. Cells were subjected to hypoxia followed by reoxygenation. UA alleviated hypoxia/reoxygenation (H/R) injury in myocardial cells, reduced myocardial infarct size and cell death in mice after ischemia/reperfusion. Meanwhile, UA enhanced antioxidant capacity in cardiomyocytes following hypoxia/reoxygenation. UA reduced myocardial apoptosis following ischemia/reperfusion. The protection of UA was abolished by LY294002, a PI3K/Akt-inhibitor. These results demonstrated that UA alleviates myocardial ischemia/reperfusion injury probably through PI3K/Akt pathway.

Keywords: Ischemia; Myocardial; PI3K/Akt; Reperfusion; Urolithin A.

MeSH terms

Animals
Animals, Newborn
Apoptosis / drug effects
Cardiotonic Agents / antagonists & inhibitors
Cardiotonic Agents / pharmacology*
Cell Survival / drug effects
Chromones / pharmacology
Coumarins / antagonists & inhibitors
Coumarins / pharmacology*
Gene Expression Regulation
Male
Mice
Mice, Inbred C57BL
Morpholines / pharmacology
Myocardial Reperfusion Injury / drug therapy*
Myocardial Reperfusion Injury / genetics
Myocardial Reperfusion Injury / metabolism
Myocardial Reperfusion Injury / pathology
Myocardium / metabolism
Myocardium / pathology
Myocytes, Cardiac / drug effects*
Myocytes, Cardiac / metabolism
Myocytes, Cardiac / pathology
Oxidative Stress / drug effects
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism
Phosphoinositide-3 Kinase Inhibitors*
Primary Cell Culture
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / genetics*
Proto-Oncogene Proteins c-akt / metabolism
Rats, Sprague-Dawley
Signal Transduction

Substances

Cardiotonic Agents
Chromones
Coumarins
Morpholines
Phosphoinositide-3 Kinase Inhibitors
3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Proto-Oncogene Proteins c-akt