Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats

Gu,Minhua; He,Peikun; Lyu,Chenfei; Liu,Xiaoyu; Xu,Yuling; Cheng,Saibo; Gu,Yong; Jia,Yuhua

doi:10.3892/mmr.2019.10686

Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats

Authors:
- Minhua Gu
- Peikun He
- Chenfei Lyu
- Xiaoyu Liu
- Yuling Xu
- Saibo Cheng
- Yong Gu
- Yuhua Jia
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Affiliations: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: September 16, 2019 https://doi.org/10.3892/mmr.2019.10686
Pages: 4253-4261
Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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