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.