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Isorhapontigenin alleviates cerebral ischemia/reperfusion injuries in rats and modulated the PI3K/Akt signaling pathway

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Abstract

Isorhapontigenin (ISO) is one of the main bioactive components of Gnetum cleistostachyum and was shown to possess antioxidant and antitumor functions. Herein, we hope to examine the neuroprotection impacts of ISO in rats subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R, 2/24 h) injuries. ISO was injected intraperitoneally into the rats immediately after cerebral ischemia. After 24 h of the reperfusion, infarct volume, brain water contents, neurological deficit, and cerebral blood flow were assessed. Hippocampus histopathology change was detected by H&E and TUNEL staining. The expressions of cleaved caspase-3, Bax and Bcl-2, and phospho-Akt (p-Akt) were investigated by real-time RT-PCR or western blot analysis. We found that ISO significantly suppressed the infarct volumes, brain water contents, and neurological deficit, increased CBF, and relieved histopathologic change in a dose-dependent manner. Reduced malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD) and GSH and glutathione peroxidase (GSH-PX) were observed in ISO group. ISO remarkably decreased caspase-3 and Bax and increased levels of Bcl-2. Additionally, ISO upregulated p-Akt expression. Blocking of PI3K activities by wortmannin can abolish the ISO-caused decrease in infarct volumes and neurologic deficit scores and abrogate the promotion of p-Akt. The data indicated that ISO played neuroprotective impacts against focal I/R injuries, possibly related to the activating of PI3K/Akt signaling.

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References

  • Abbas AM (2016) Cardioprotective effect of resveratrol analogue isorhapontigenin versus omega-3 fatty acids in isoproterenol-induced myocardial infarction in rats. J Physiol Biochem 72:469–484

    Article  CAS  Google Scholar 

  • Aronowski J, Strong R, Grotta JC (1997) Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. J Cereb Blood Flow Metab 17:1048–1056

    Article  CAS  Google Scholar 

  • Fang Y, Yu Y, Hou Q, Zheng X, Zhang M, Zhang D, Li J, Wu XR, Huang C (2012) The Chinese herb isolate isorhapontigenin induces apoptosis in human cancer cells by down-regulating overexpression of antiapoptotic protein XIAP. J Biol Chem 287:35234–35243

    Article  CAS  Google Scholar 

  • Fang L, Gao H, Zhang W, Zhang W, Wang Y (2015) Resveratrol alleviates nerve injury after cerebral ischemia and reperfusion in mice by inhibiting inflammation and apoptosis. Int J Clin Exp Med 8:3219

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gray JJ, Bickler PE, Fahlman CS, Zhan X, Schuyler JA (2005) Isoflurane neuroprotection in hypoxic hippocampal slice cultures involves increases in intracellular Ca2+ and mitogen-activated protein kinases. Anesthesiology 102:606–615

    Article  CAS  Google Scholar 

  • Huang J, Upadhyay UM, Tamargo RJ (2006) Inflammation in stroke and focal cerebral ischemia. Surg Neurol 66:232–245

    Article  Google Scholar 

  • Hung L-M, Su M-J, Chen J-K (2004) Resveratrol protects myocardial ischemia–reperfusion injury through both NO-dependent and NO-independent mechanisms. Free Radic Biol Med 36:774–781

    Article  CAS  Google Scholar 

  • Jean WC, Spellman SR, Nussbaum ES, Low WC (1998) Reperfusion injury after focal cerebral ischemia: the role inflammation and the The rapeutic Horizon. Neurosurgery 43:1382–1396

    CAS  PubMed  Google Scholar 

  • Li H-L, Wang AB, Huang Y, Liu DP, Wei C, Williams GM, Zhang CN, Liu G, Liu YQ, Hao DL, Hui RT, Lin M, Liang CC (2005) Isorhapontigenin, a new resveratrol analog, attenuates cardiac hypertrophy via blocking signaling transduction pathways. Free Radic Biol Med 38:243–257

    Article  Google Scholar 

  • Lin Y, Chen F, Zhang J, Wang T, Wei X, Wu J, Feng Y, Dai Z, Wu Q (2013) Neuroprotective effect of resveratrol on ischemia/reperfusion injury in rats through TRPC6/CREB pathways. J Mol Neurosci 50:504–513

    Article  CAS  Google Scholar 

  • Liu Y, Liu G (2004) Isorhapontigenin and resveratrol suppress oxLDL-induced proliferation and activation of ERK1/2 mitogen-activated protein kinases of bovine aortic smooth muscle cells. Biochem Pharmacol 67:777–785

    Article  CAS  Google Scholar 

  • Ray PS, Maulik G, Cordis GA, Bertelli AA, Bertelli A, Das DK (1999) The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radic Biol Med 27:160–169

    Article  CAS  Google Scholar 

  • Shen M et al (2012) Resveratrol attenuates ischemia/reperfusion injury in neonatal cardiomyocytes and its underlying mechanism. PLoS One 7:e51223

    Article  CAS  Google Scholar 

  • Soriano SG, Coxon A, Wang YF, Frosch MP, Lipton SA, Hickey PR, Mayadas TN (1999) Mice deficient in mac-1 (CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury. Stroke 30:134–139

    Article  CAS  Google Scholar 

  • Wang QL, Lin M, Liu GT (2001) Antioxidative activity of natural isorhapontigenin. Jpn J Pharmacol 87:61–66

    Article  CAS  Google Scholar 

  • Wang HY, Wang GL, Yu YH, Wang Y (2009) The role of phosphoinositide-3-kinase/Akt pathway in propofol-induced postconditioning against focal cerebral ischemia-reperfusion injury in rats. Brain Res 1297:177–184. https://doi.org/10.1016/j.brainres.2009.08.054

    Article  CAS  PubMed  Google Scholar 

  • Wang J-K, Yu L-N, Zhang F-J, Yang M-J, Yu J, Yan M, Chen G (2010) Postconditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury via PI3K/Akt pathway. Brain Res 1357:142–151

    Article  CAS  Google Scholar 

  • Xu X, Chua CC, Gao J, Chua K-W, Wang H, Hamdy RC, Chua BH (2008) Neuroprotective effect of humanin on cerebral ischemia/reperfusion injury is mediated by a PI3K/Akt pathway. Brain Res 1227:12–18

    Article  CAS  Google Scholar 

  • Zhang X et al (2013) Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. Autophagy 9:1321–1333

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Neurology Department, Sishui County People’s Hospital, Jining City, Shandong province, 273200, People’s Republic of China

    Xin Sun

  2. Pediatric Department, The Affiliated Hospital of Jining Medical University, No. 89 Guhuai Road, Jining City, Shandong province, 272029, People’s Republic of China

    Xin Cui

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  1. Xin Sun
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  2. Xin Cui
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Correspondence to Xin Cui.

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Animal Care and Use Committee of The Affiliated Hospital of Jining Medical University approved all our experiments. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Sun, X., Cui, X. Isorhapontigenin alleviates cerebral ischemia/reperfusion injuries in rats and modulated the PI3K/Akt signaling pathway. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1753–1760 (2020). https://doi.org/10.1007/s00210-019-01794-0

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