Scutellarin Ameliorates Learning and Memory Deficit via Suppressing beta-Amyloid Formation and Microglial Activation in Rats with Chronic Cerebral Hypoperfusion

摘要

Chronic cerebral hypoperfusion is considered as a pivotal factor of cognitive impairment that occurs in cerebrovascular diseases. This study investigated the ameliorating effect of scutellarin (SCT) on spatial cognitive impairment and beta-amyloid (A beta) formation in rats with chronic cerebral hypoperfusion induced by permanent bilateral common carotid artery occlusion (pBCAO). SCT is a flavonoid in medicinal herb of Erigeron breviscapus (vant.) Hand. Mazz. known to have neuroprotective, antioxidative and anti-inflammatory effects. However, the beneficial effect and pivotal mechanism of SCT on cognitive impairment are still unclear. SCT was treated orally with two doses (10 or 30 mg/kg) for 4 weeks. Results of Morris water maze test performed on the ninth week after pBCAO revealed that SCT (30 mg/kg)-treated rats had significantly shortened escape latencies in acquisition training trials, significantly prolonged swimming time at the platform and its surrounding zone, significant increase in memory score, significant reduction in the number of target heading, and significant reduction in the time required for the first target heading during the retention trial compared to rats in the sham-control group. SCT significantly inhibited the production of A beta((1-40)) and A beta((1-42)) in brain tissues. However, SCT significantly upregulated the expression levels of amyloid precursor protein and beta-site APP-converting enzyme-1 in the hippocampus. In addition, SCT significantly inhibited the activation of Ibal-expressing microglia in brain tissues. The results suggest that SCT can exert ameliorating effect on spatial cognitive impairment caused by chronic cerebral hypoperfusion through suppressing A beta formation and microglial activation in brain tissues. Therefore, SCT can be used as a beneficial drug for vascular dementia and Alzheimer's disease.