Hispidulin Protects Against Focal Cerebral Ischemia Reperfusion Injury in Rats
- 115 Downloads
Focal cerebral ischemia is associated with ischemia/reperfusion (I/R) injury. Hispidulin is a flavonoid compound with a variety of pharmacological properties. The neuroprotective effects of hispidulin have not been fully elucidated. Herein, we demonstrated that pretreatment of animals with hispidulin improved the neurological outcomes and decreased the infarct size and brain edema in the cerebral focal I/R model. Mechanistically, we showed in vivo and in vitro that hispidulin exerted a protective effect against I/R injury by inducing the Nrf2 antioxidant pathway through modulation of AMPK/GSK3β signaling. Taken together, our results suggest that hispidulin may be a useful neuroprotective agent against ischemia/reperfusion (I/R) injury.
KeywordsHispidulin Ischemia/reperfusion (I/R) injury Nrf2 AMPK/GSK3β
The study was supported by Shandong Province Chinese Medicine Science and Technology Development Project (2017-321) and Qingdao medical scientific research guidance program (2016-WJZD024).
Compliance with Ethical Standards
The experimental protocol was approved by the Medical Ethics Committee of The Affiliated Qingdao Hiser Hospital of Qingdao University.
Conflict of Interest
The authors declare that they have no conflict of interest.
- Duan J, Yin Y, Cui J, Yan J, Zhu Y, Guan Y, Wei G, Weng Y, Wu X, Guo C, Wang Y, Xi M, Wen A (2016) Chikusetsu saponin IVa ameliorates cerebral ischemia reperfusion injury in diabetic mice via adiponectin-mediated AMPK/GSK-3beta pathway in vivo and in vitro. Mol Neurobiol 53(1):728–743. https://doi.org/10.1007/s12035-014-9033-x CrossRefPubMedGoogle Scholar
- Gursoy-Ozdemir Y, Can A, Dalkara T (2004) Reperfusion-induced oxidative/nitrative injury to neurovascular unit after focal cerebral ischemia. Stroke 35(6):1449–1453. https://doi.org/10.1161/01.STR.0000126044.83777.f4 CrossRefPubMedGoogle Scholar
- Kavvadias D, Sand P, Youdim KA, Qaiser MZ, Rice-Evans C, Baur R, Sigel E, Rausch WD, Riederer P, Schreier P (2004) The flavone hispidulin, a benzodiazepine receptor ligand with positive allosteric properties, traverses the blood-brain barrier and exhibits anticonvulsive effects. Br J Pharmacol 142(5):811–820. https://doi.org/10.1038/sj.bjp.0705828 CrossRefPubMedPubMedCentralGoogle Scholar
- Li M, Zhang X, Cui L, Yang R, Wang L, Liu L, Du W (2011) The neuroprotection of oxymatrine in cerebral ischemia/reperfusion is related to nuclear factor erythroid 2-related factor 2 (nrf2)-mediated antioxidant response: role of nrf2 and hemeoxygenase-1 expression. Biol Pharm Bull 34(5):595–601CrossRefPubMedGoogle Scholar
- Song JS, Kim EK, Choi YW, Oh WK, Kim YM (2016) Hepatocyte-protective effect of nectandrin B, a nutmeg lignan, against oxidative stress: role of Nrf2 activation through ERK phosphorylation and AMPK-dependent inhibition of GSK-3beta. Toxicol Appl Pharmacol 307:138–149. https://doi.org/10.1016/j.taap.2016.08.003 CrossRefPubMedGoogle Scholar
- Urakawa S, Hida H, Masuda T, Misumi S, Kim TS, Nishino H (2007) Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats. Neuroscience 144(3):920–933. https://doi.org/10.1016/j.neuroscience.2006.10.038 CrossRefPubMedGoogle Scholar
- Vereczki V, Martin E, Rosenthal RE, Hof PR, Hoffman GE, Fiskum G (2006) Normoxic resuscitation after cardiac arrest protects against hippocampal oxidative stress, metabolic dysfunction, and neuronal death. J Cereb Blood Flow Metab 26(6):821–835. https://doi.org/10.1038/sj.jcbfm.9600234 CrossRefPubMedPubMedCentralGoogle Scholar
- Wang P, Xu TY, Guan YF, Tian WW, Viollet B, Rui YC, Zhai QW, Su DF, Miao CY (2011) Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway. Ann Neurol 69(2):360–374. https://doi.org/10.1002/ana.22236 CrossRefPubMedGoogle Scholar