Novel GSK-3β Inhibitor Neopetroside A Protects Against Murine Myocardial Ischemia/Reperfusion Injury
Hyoung Kyu Kim, Min Kim, Jubert Marquez, Seung Hun Jeong, Tae Hee Ko, Yeon Hee Noh, Pham Trong Kha, Ha Min Choi, Dong‐Hyun Kim, Jong‐Tae Kim, Young Il Yang, Kyung Soo Ko, Byoung Doo Rhee, Larisa K. Shubina, Tatyana N. Makarieva, Dmitry Y. Yashunsky, Alexey G. Gerbst, Nikolay E. Nifantiev, Valentin A. Stonik, Jin Han
Abstract
Recent trends suggest novel natural compounds as promising treatments for cardiovascular disease. The authors examined how neopetroside A, a natural pyridine nucleoside containing an α-glycoside bond, regulates mitochondrial metabolism and heart function and investigated its cardioprotective role against ischemia/reperfusion injury. Neopetroside A treatment maintained cardiac hemodynamic status and mitochondrial respiration capacity and significantly prevented cardiac fibrosis in murine models. These effects can be attributed to preserved cellular and mitochondrial function caused by the inhibition of glycogen synthase kinase-3 beta, which regulates the ratio of nicotinamide adenine dinucleotide to nicotinamide adenine dinucleotide, reduced, through activation of the nuclear factor erythroid 2-related factor 2/NAD(P)H quinone oxidoreductase 1 axis in a phosphorylation-independent manner.