Acer okamotoanum and isoquercitrin improve cognitive function via attenuation of oxidative stress in high fat diet- and amyloid beta-induced mice
Obesity induced by high-fat diet (HFD) and accumulation of amyloid beta (Aβ) are known as a risk factor of Alzheimer’s disease. We previously identified isoquercitrin (IQ) as an active compound of Acer okamotoanum. In the present study, we investigated protective effects of active ethylacetate (EtOAc) fraction from A. okamotoanum and IQ on the HFD and Aβ25-35-induced cognitive impairment mice. C57BL/6J mice were fed with HFD for 10 weeks and then Aβ25-35 was injected intracerebroventricular (i.c.v.). The EtOAc fraction of A. okamotoanum and IQ were administered orally for 4 weeks at 100 mg/kg/day and 10 mg/kg/day, respectively. Learning and memory functions were evaluated using behavioral tests including T-maze, object recognition and Morris water maze test. The HFD and Aβ25-35 injection significantly impaired cognitive and memory function. However, administration of A. okamotoanum and IQ improved spatial cognition ability and object recognition ability in T-maze and novel object recognition test. In addition, A. okamotoanum and IQ–administered groups enhanced learning and memory function, compared with HFD and Aβ25-35-induced cognitive impairment mice in Morris water maze test. Furthermore, administration of A. okamotoanum and IQ attenuated oxidative stress in the brain via inhibition of reactive oxygen species production, lipid peroxidation, and nitric oxide formation. Therefore, we suggest that A. okamotoanum and IQ improve HFD- and Aβ25-35-induced cognitive impairment by inhibition of oxidative stress, and A. okamotoanum and IQ might be potential candidates for prevention or treatment of obesity- and Aβ-induced cognitive impairment.