Effects of (-)Epicatechin on the Pathology of APP/PS1 Transgenic Mice.

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The clearance of Aß from the brain and anti-inflammation are potential important strategies to prevent and treat disease. In a previous study, we demonstrated the grape seed extract (GSE) could reduce brain Aß burden and microglia activation, but which polyphenol plays a major role in these events is not known. Here, we tested pharmacological effects of (-)epicatechin, one principle polyphenol compound in GSE, on transgenic AD mice. METHODS: APP/PS1 transgenic mice were fed with (-)epicatechin diet (40 mg/kg/day) and curcumin diet (47 mg/kg/day) at 3 months of age for 9 months, the function of liver, Aß levels in the brain and serum, AD-type neuropathology, plasma levels of inflammatory cytokines were measured. RESULTS: Toward the end of the experiment, we found long-term feeding of (-)epicatechin diet was well tolerated without fatality, changes in food consumption, body weight, or liver function. (-)Epicatechin significantly reduced total Aß in brain and serum by 39 and 40%, respectively, compared with control diet. Microgliosis and astrocytosis in the brain of Alzheimer's mice were also reduced by 38 and 35%, respectively. The (-)epicatechin diet did not alter learning and memory behaviors in AD mice. CONCLUSION: This study has provided evidence on the beneficial role of (-)epicatechin in ameliorating amyloid-induced AD-like pathology in AD mice, but the impact of (-)epicatechin on tau pathology is not clear, also the mechanism needs further research.