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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
  • View Affiliations / Copyright

    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
    Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4253-4261
    |
    Published online on: September 16, 2019
       https://doi.org/10.3892/mmr.2019.10686
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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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1 

Frank A, Bonney M, Bonney S, Weitzel L, Koeppen M and Eckle T: Myocardial ischemia reperfusion injury: From basic science to clinical bedside. Semin Cardiothorac Vasc Anesth. 16:123–132. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Binder A, Ali A, Chawla R, Aziz HA, Abbate A and Jovin IS: Myocardial protection from ischemia-reperfusion injury post coronary revascularization. Expert Rev Cardiovasc Ther. 13:1045–1057. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Cao JX, Zhang QY, Cui SY, Cui XY, Zhang J, Zhang YH, Bai YJ and Zhao YY: Hypnotic effect of jujubosides from Semen Ziziphi Spinosae. J Ethnopharmacol. 130:163–166. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Jia YH, Zhang YX, Li LJ, Liu YW, Li CH, Fu XQ, Zeng P, Wu WK and Sun XG: Dingxin recipe prevents ischemia/reperfusion-induced arrhythmias via up-regulating prohibitin and suppressing inflammatory responses. Chin J Integr Med. 18:120–129. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Liu J, Zhai WM, Yang YX, Shi JL, Liu QT, Liu GL, Fang N, Li J and Guo JY: GABA and 5-HT systems are implicated in the anxiolytic-like effect of spinosin in mice. Pharmacol Biochem Behav. 128:41–49. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Lee Y, Jeon SJ, Lee HE, Jung IH, Jo YW, Lee S, Cheong JH, Jang DS and Ryu JH: Spinosin, a C-glycoside flavonoid, enhances cognitive performance and adult hippocampal neurogenesis in mice. Pharmacol Biochem Behav. 145:9–16. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Ko SY, Lee HE, Park SJ, Jeon SJ, Kim B, Gao Q, Jang DS and Ryu JH: Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. Spinosa ameliorates abeta1-42 oligomer-induced memory impairment in Mice. Biomol Ther (Seoul). 23:156–164. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Xu F, He B, Xiao F, Yan T, Bi K, Jia Y and Wang Z: Neuroprotective effects of spinosin on recovery of learning and memory in a mouse model of Alzheimer's disease. Biomol Ther (Seoul). 27:71–77. 2019. View Article : Google Scholar : PubMed/NCBI

9 

Wang J, Yang H, Hu X, Fu W, Xie J, Zhou X, Xu W and Jiang H: Dobutamine-mediated heme oxygenase-1 induction via PI3K and p38 MAPK inhibits high mobility group box 1 protein release and attenuates rat myocardial ischemia/reperfusion injury in vivo. J Surg Res. 183:509–516. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Guo X, Cao W, Yao J, Yuan Y, Hong Y, Wang X and Xing J: Cardioprotective effects of tilianin in rat myocardial ischemia-reperfusion injury. Mol Med Rep. 11:2227–2233. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Colareda GA and Consolini AE: Low-flow ischaemia and reperfusion in rat hearts: Energetic of stunning and cardioprotection of genistein. J Pharm Pharmacol. 70:1174–1187. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Dou MM, Zhang ZH, Li ZB, Zhang J and Zhao XY: Cardioprotective potential of Dendrobium officinale Kimura et Migo against myocardial ischemia in mice. Mol Med Rep. 14:4407–4414. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Djavaheri-Mergny M, Amelotti M, Mathieu J, Besançon F, Bauvy C, Souquère S, Pierron G and Codogno P: NF-kappaB activation represses tumor necrosis factor-alpha-induced autophagy. J Biol Chem. 281:30373–30382. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Bravo-San Pedro JM, Kroemer G and Galluzzi L: Autophagy and mitophagy in cardiovascular disease. Circ Res. 120:1812–1824. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Weikel KA, Cacicedo JM, Ruderman NB and Ido Y: Knockdown of GSK3β increases basal autophagy and AMPK signalling in nutrient-laden human aortic endothelial cells. Biosci Rep. 36(pii): e003822016. View Article : Google Scholar : PubMed/NCBI

16 

Juhaszova M, Zorov DB, Yaniv Y, Nuss HB, Wang S and Sollott SJ: Role of glycogen synthase kinase-3beta in cardioprotection. Circ Res. 104:1240–1252. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Romano B, Pagano E, Montanaro V, Fortunato AL, Milic N and Borrelli F: Novel insights into the pharmacology of flavonoids. Phytother Res. 27:1588–1596. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Sinning C, Westermann D and Clemmensen P: Oxidative stress in ischemia and reperfusion: Current concepts, novel ideas and future perspectives. Biomark Med. 11:11031–11040. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Zorov DB, Juhaszova M and Sollott SJ: Mitochondrial ROS-induced ROS release: An update and review. Biochim Biophys Acta. 1757:509–517. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Ghaderi S, Alidadiani N, Dilaver N, Heidari HR, Parvizi R, Rahbarghazi R, Soleimani-Rad J and Baradaran B: Role of glycogen synthase kinase following myocardial infarction and ischemia-reperfusion. Apoptosis. 22:887–897. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Marchand B, Arsenault D, Raymond-Fleury A, Boisvert FM and Boucher MJ: Glycogen synthase kinase-3 (GSK3) inhibition induces prosurvival autophagic signals in human pancreatic cancer cells. J Biol Chem. 290:5592–5605. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Choi HI, Kim HJ, Park JS, Kim IJ, Bae EH, Ma SK and Kim SW: PGC-1α attenuates hydrogen peroxide-induced apoptotic cell death by upregulating Nrf-2 via GSK3β inactivation mediated by activated p38 in HK-2 Cells. Sci Rep. 7:43192017. View Article : Google Scholar : PubMed/NCBI

23 

Boya P, Reggiori F and Codogno P: Emerging regulation and functions of autophagy. Nat Cell Biol. 15:713–720. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Rabinowitz JD and White E: Autophagy and metabolism. Science. 330:1344–1348. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Zhang YJ, Yang SH, Li MH, Iqbal J, Bourantas CV, Mi QY, Yu YH, Li JJ, Zhao SL, Tian NL and Chen SL: Berberine attenuates adverse left ventricular remodeling and cardiac dysfunction after acute myocardial infarction in rats: Role of autophagy. Clin Exp Pharmacol Physiol. 41:995–1002. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Lin C, Liu Z, Lu Y, Yao Y, Zhang Y, Ma Z, Kuai M, Sun X, Sun S, Jing Y, et al: Cardioprotective effect of Salvianolic acid B on acute myocardial infarction by promoting autophagy and neovascularization and inhibiting apoptosis. J Pharm Pharmacol. 68:941–952. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Rogov V, Dotsch V, Johansen T and Kirkin V: Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol Cell. 53:167–178. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Gottlieb RA: Autophagy in health and diseaseAcademic Press; London, Waltham, MA: 2013

29 

Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM and Kelly DP: Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest. 106:847–856. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A and Reed SI: SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis. Genes Dev. 22:252–264. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Xu R, Hu Q, Ma Q, Liu C and Wang G: The protease Omi regulates mitochondrial biogenesis through the GSK3β/PGC-1α pathway. Cell Death Dis. 5:e13732014. View Article : Google Scholar : PubMed/NCBI

32 

Loboda A, Damulewicz M, Pyza E, Jozkowicz A and Dulak J: Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: An evolutionarily conserved mechanism. Cell Mol Life Sci. 73:3221–3247. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Qiao L, Liu Y, Chen X, Xie J, Zhang Y, Yang K, Zhou H, Duan Y, Zheng W and Xie W: A HPLC-MS/MS method for determination of 6‴-feruloylspinosin in rat plasma and tissues: Pharmacokinetics and tissue distribution study. J Pharm Biomed Anal. 121:77–83. 2016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Gu M, He P, Lyu C, Liu X, Xu Y, Cheng S, Gu Y and Jia Y: Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats. Mol Med Rep 20: 4253-4261, 2019.
APA
Gu, M., He, P., Lyu, C., Liu, X., Xu, Y., Cheng, S. ... Jia, Y. (2019). Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats. Molecular Medicine Reports, 20, 4253-4261. https://doi.org/10.3892/mmr.2019.10686
MLA
Gu, M., He, P., Lyu, C., Liu, X., Xu, Y., Cheng, S., Gu, Y., Jia, Y."Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats". Molecular Medicine Reports 20.5 (2019): 4253-4261.
Chicago
Gu, M., He, P., Lyu, C., Liu, X., Xu, Y., Cheng, S., Gu, Y., Jia, Y."Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats". Molecular Medicine Reports 20, no. 5 (2019): 4253-4261. https://doi.org/10.3892/mmr.2019.10686
Copy and paste a formatted citation
x
Spandidos Publications style
Gu M, He P, Lyu C, Liu X, Xu Y, Cheng S, Gu Y and Jia Y: Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats. Mol Med Rep 20: 4253-4261, 2019.
APA
Gu, M., He, P., Lyu, C., Liu, X., Xu, Y., Cheng, S. ... Jia, Y. (2019). Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats. Molecular Medicine Reports, 20, 4253-4261. https://doi.org/10.3892/mmr.2019.10686
MLA
Gu, M., He, P., Lyu, C., Liu, X., Xu, Y., Cheng, S., Gu, Y., Jia, Y."Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats". Molecular Medicine Reports 20.5 (2019): 4253-4261.
Chicago
Gu, M., He, P., Lyu, C., Liu, X., Xu, Y., Cheng, S., Gu, Y., Jia, Y."Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats". Molecular Medicine Reports 20, no. 5 (2019): 4253-4261. https://doi.org/10.3892/mmr.2019.10686
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