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19 August 2017 : Animal Research  

Apigenin Ameliorates Post-Stroke Cognitive Deficits in Rats Through Histone Acetylation-Mediated Neurochemical Alterations

Fengxia Tu1BCE, Qiongyi Pang1BCD, Tingting Huang1BCD, Yun Zhao1BCD, Meixia Liu1CDF, Xiang Chen1AG*

DOI: 10.12659/MSM.902770

Med Sci Monit 2017; 23:4004-4013

Abstract

BACKGROUND: To identify the effect of apigenin on cognitive deficits of rats after cerebral ischemia and reperfusion injury, and to investigate the potential molecular mechanisms.

MATERIAL AND METHODS: The rats were given sodium butyrate (NaB) or apigenin (20 or 40 mg/kg) for 28 days. Cognition was investigated by the Morris water maze (MWM) test. On day 28, the rats were euthanized and their hippocampal brain regions were used to identify biochemical and neurochemical alterations. The content of histone deacetylase (HDAC) was measured by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to determine the levels of BDNF, phosphorylated cAMP response element-binding protein (pCREB), acetylated H3, and acetylated H4. The mRNA expressions of brain-derived neurotrophic factor (BDNF) and synapsin-I (Syn-I) were examined by polymerase chain reaction (PCR).

RESULTS: The rats with chronic administration of apigenin (20 and 40 mg/kg) showed better performance in the MWM task than the model rats; there was no significant difference between the apigenin-treated and NaB-treated rats. At the higher apigenin dose of 40 mg/kg, the HDAC content was decreased, the BDNF level was markedly increased, and acetylated H3 and acetylated H4 expressions and Syn-I expressions in the hippocampus was upregulated compared with the model group. Apigenin at 20 mg/kg did not show reversal of the neurochemical alterations.

CONCLUSIONS: The improvement effect of apigenin on cognitive impairments after cerebral ischemia and reperfusion injury may involve multiple mechanisms, such as the inhibition of HDAC, induction of BDNF and Syn-I expression, and regulation of histone acetylation.

Keywords: Apigenin, Brain-Derived Neurotrophic Factor, Histone Deacetylases, Infarction, Middle Cerebral Artery, Memory Disorders

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750