JACC: Basic to Translational Science (Nov 2022)
Novel GSK-3β Inhibitor Neopetroside A Protects Against Murine Myocardial Ischemia/Reperfusion Injury
- Hyoung Kyu Kim, PhD,
- Min Kim, PhD,
- Jubert C. Marquez, PhD,
- Seung Hun Jeong, PhD,
- Tae Hee Ko, PhD,
- Yeon Hee Noh, MS,
- Pham Trong Kha, PhD,
- Ha Min Choi, BS,
- Dong Hyun Kim, PhD,
- Jong Tae Kim, PhD,
- Young Il Yang, PhD,
- Kyung Soo Ko, PhD,
- Byoung Doo Rhee, PhD,
- Larisa K. Shubina, PhD,
- Tatyana N. Makarieva, PhD,
- Dmitry Y. Yashunsky, PhD,
- Alexey G. Gerbst, PhD,
- Nikolay E. Nifantiev, PhD,
- Valentin A. Stonik, PhD,
- Jin Han, PhD
Affiliations
- Hyoung Kyu Kim, PhD
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Health Sciences and Technology, Graduate School, Inje University, Busan, South Korea
- Min Kim, PhD
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Physiology, BK Plus Project Team, College of Medicine, Inje University, Busan, South Korea
- Jubert C. Marquez, PhD
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Health Sciences and Technology, Graduate School, Inje University, Busan, South Korea
- Seung Hun Jeong, PhD
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Physiology, BK Plus Project Team, College of Medicine, Inje University, Busan, South Korea
- Tae Hee Ko, PhD
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Physiology, BK Plus Project Team, College of Medicine, Inje University, Busan, South Korea
- Yeon Hee Noh, MS
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Physiology, BK Plus Project Team, College of Medicine, Inje University, Busan, South Korea
- Pham Trong Kha, PhD
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Physiology, BK Plus Project Team, College of Medicine, Inje University, Busan, South Korea
- Ha Min Choi, BS
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Physiology, BK Plus Project Team, College of Medicine, Inje University, Busan, South Korea
- Dong Hyun Kim, PhD
- Department of Pharmacology and Pharmaco-Genomics Research Center, College of Medicine, Inje University, Busan, South Korea
- Jong Tae Kim, PhD
- Paik Institute for Clinical Research, Inje University College of Medicine, Busan, South Korea
- Young Il Yang, PhD
- Paik Institute for Clinical Research, Inje University College of Medicine, Busan, South Korea
- Kyung Soo Ko, PhD
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Health Sciences and Technology, Graduate School, Inje University, Busan, South Korea
- Byoung Doo Rhee, PhD
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Health Sciences and Technology, Graduate School, Inje University, Busan, South Korea
- Larisa K. Shubina, PhD
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok, Russia
- Tatyana N. Makarieva, PhD
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok, Russia
- Dmitry Y. Yashunsky, PhD
- Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
- Alexey G. Gerbst, PhD
- Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
- Nikolay E. Nifantiev, PhD
- Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
- Valentin A. Stonik, PhD
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok, Russia
- Jin Han, PhD
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea; Department of Health Sciences and Technology, Graduate School, Inje University, Busan, South Korea; Department of Physiology, BK Plus Project Team, College of Medicine, Inje University, Busan, South Korea; Address for correspondence: Dr Jin Han, National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47393, South Korea.
- Journal volume & issue
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Vol. 7,
no. 11
pp. 1102 – 1116
Abstract
Summary: 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.
