Cerebrovascular protection of β-asarone in Alzheimer's disease rats: a behavioral, cerebral blood flow, biochemical and genic study.

OBJECTIVE

Recent studies have suggested that β-asarone have neuroprotective and cardiovascular protective effects in animal model. However, the influence of β-asarone on cerebrovascular system has not been explored so far. Therefore, present study was designed to determine whether repeated exposures to β-asarone resulted in positive effects on cerebrovascular function in AD rats.

METHODS

Alzheimer's disease induced rats was established by injecting both D-galactose (D-gal) and aluminum chloride (AlCl(3)) into abdominal cavity for 42 days. After injection of AlCl(3) and D-gal or saline for 28 days, the rats were treated with volume-matched vehicle or β-asarone (25mg/kg, 50mg/kg or 100mg/kg, i.h.) or Nimodipine (40mg/kg, i.g) once daily for consecutive 14 days, respectively. Behavioral responses of animals were assessed in a Morris water maze. CBF was measured by laser Doppler flowmetry. At the end of this period all rats were sacrificed, lactic acid, pyruvic acid content, Na+K+ATPase activity were determined in brain tissue homogenate to estimate the brain biochemical changes and mRNA expression of ET-1, eNOS and APP was measured with real-time RT-PCR method.

RESULTS

The spatial navigation task latencies, the times through platform zone and the time for the first through platform zone in the target quadrant in probe task, rCBF of right parietal lobe, the contents of lactic acid, pyruvic acid, and the activity of Na-K-ATP of cortex, and ET-1 and eNOS mRNA expression in hippocampus of AG rats were different from those of BG, P<0.05; The level of APP mRNA expression in model control group rats was higher than that in BG, though there was not a statistically significant difference, P>0.05; Compared with AG, HG rats spatial navigation task latencies were shorter, in probe task the times through platform zone in the target quadrant were bigger, rCBF and blood cell concentration of right parietal lobe were higher, the contents of pyruvic acid was lower, the activity of Na-K-ATP was higher, and ET-1 mRNA expression in hippocampus was lower, P<0.05; The level of eNOS and APP mRNA expression in HG rats was lower than that in AG, though there was not a statistically significant difference, P>0.05;

CONCLUSIONS

The present results suggested that β-asarone may be useful in memory impairment due to its cerebrovascular protection in AD rats and may develop as a therapeutic drug for treatment of AD patients.