Spinosin and 6''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats
Autor: | Xiaoyu Liu, Yu-Ling Xu, Minhua Gu, Jia Yuhua, Yong Gu, Chenfei Lyu, Pei-Kun He, Saibo Cheng |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cardiac function curve Male Cancer Research autophagy Myocardial Ischemia SZS Apoptosis Myocardial Reperfusion Injury Pharmacology Biochemistry AMI 03 medical and health sciences 0302 clinical medicine spinosin Genetics medicine Myocyte Animals Myocytes Cardiac Myocardial infarction Phosphorylation Receptor Glycogen synthase Molecular Biology Flavonoids Glycogen Synthase Kinase 3 beta Oncogene biology Molecular Structure business.industry GSK3β Heart Articles medicine.disease Molecular medicine Rats Disease Models Animal 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Molecular Medicine business Biomarkers Drugs Chinese Herbal Signal Transduction |
Zdroj: | Molecular Medicine Reports |
ISSN: | 1791-3004 |
Popis: | Investigating active compounds from Chinese herbal medicine that can rescue myocardial cells is a good approach to preserve cardiac function. Several herbal formulae that containing Semen Ziziphi Spinosae (SZS), also called Suanzaoren in Chinese, are clinically effective in the treatment of patients with acute myocardial infarction (AMI). The present study aimed to investigate the cardioprotective effects of spinosin and 6'''‑feruloylspinosin, two flavonoid glycosides from SZS, in a rat model of myocardial ischemia and reperfusion. The left anterior descending artery (LAD) was occluded to induce myocardial ischemia. Spinosin or 6'''‑feruloylspinosin (5 mg/kg) was intraperitoneally injected into rats 30 min before LAD ligation. The protein levels of myocardial enzymes in the serum, the extent of tissue injury and the rate of apoptosis were examined after AMI in rats with or without pretreatment with spinosin or 6'''‑feruloylspinosin. Western blotting was performed to investigate the potential mechanisms underlying the function of these two flavonoid glycosides. The present results suggested that pretreatment with spinosin or 6'''‑feruloylspinosin significantly attenuated myocardial tissue injury, and reduced myocardial enzyme release and cell apoptosis in AMI rats. In addition, spinosin treatment increased light chain 3B‑II and 6'''‑feruloylspinosin, and reduced p62, indicating that autophagy was promoted after drug treatments. Treatments of spinosin and 6'''‑feruloylspinosin led to the reduction of glycogen synthase kinase‑3β (GSK3β) phosphorylation at Tyr216, and the increase of peroxisome proliferator‑activated receptor γ coactivator (PGC)‑1α and its downstream signaling proteins, including nuclear factor (erythroid‑derived 2)‑like 2 (Nrf2) and hemeoxygenase1 (HO‑1). The present data suggested that SZS flavonoids could protect myocardial cells against acute heart ischemia‑reperfusion, probably via the inhibition of GSK3β, which increased autophagy and the activity of the PGC‑1α/Nrf2/HO‑1 pathway. |
Databáze: | OpenAIRE |
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