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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2017, Vol. 22 ›› Issue (9): 1002-1007.

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Effect of fisetin on learning and memory impairment induced by cerebral ischemia reperfusion and HPA axis

ZHU Jiejin, WU Yong, YE Xiaoli, YE Huajin, WANG Gang, FEI Fei   

  1. Department of Pharmacy, Hangzhou First People's Hospital, Hangzhou Hospital Affiated to Nanjing Medical University,Hangzhou 310006, Zhejiang, China
  • Received:2017-01-06 Revised:2017-02-08 Online:2017-09-26 Published:2017-09-30

Abstract:

AIM: To investigate the effect of fisetin on learning memorial ability deficit after cerebral ischemia reperfusion and its possible mechanism.  METHODS: Adult male Wistar rats were randomly divided into seven groups: the sham operation, the IR model group, fisetin group(10, 20, 40 mg/kg, p.o.). The four-vessel occlusion method was used to build rat model of cerebral ischemia reperfusion. All rats were tested for Morris water maze(MWM). The serum level of corticosterone was detected using the enzyme linked immunosorbent assay. At the end, the expressions of corticotropin releasing hormone (CRH) mRNA and glucocorticoid receptor (GR) mRNA in the hippocampus were analyzed by RT-PCR and semi-quantitative in situ hybridization, respectively. RESULTS:Compared with the sham group, the learning ability of the IR rats decreased significantly (P<0.01), fisetin(20, 40 mg/kg)could improve the ability of learning memory significantly(P<0.05 or P<0.01). The serum level of corticosterone increased in IR rats, and fisetin(20, 40 mg/kg)could also decline the level of this stress hormone(P<0.05). At the end, the expression of CRH mRNA in the hippocampus of IR rats was increased and fisetin(40 mg/kg)reversed the expression of this gene(P<0.05); the GR receptor expressions in the hippocampus was reduced and fisetin(40 mg/kg)reversed these changes in IR rats(P<0.05).CONCLUSION: Fisetin reverses the learning memory damage after cerebral ischemia reperfusion injury, and the mechanism may be mediated by regulating the function of the hypothalamo-pituitary-adrenal (HPA) axis and the expression.

Key words: fisetin, HPA axis, cerebral ischemia reperfusion, corticotropin releasing hormone

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