Comparison of protective effects of four polyphenols on neuropathology and behavior of APP/PS1-21 transgenic mice, a model of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is one of the most important neurodegenerative disorders, bringing about huge medical and social burden worldwide. It is a multifactorial disease, clinically characterized by progressive cognitive loss, neuropsychiatric and behavioral disorders. Neuropathological examination of the brains of AD patients reveals extracellular amyloid beta (Aβ) plaques in brain parenchyma and increased neuro-inflammation. Natural polyphenols, most common compounds in foods and herbal beverages, are a large class of phytochemical that are composed of aromatic and one or more phenolic rings. Four polyphenolic compounds (namely Hesperidin, Icariin, Dihydromyricetin and Baicalin) with potential neuroprotective properties were selected for further evaluation. In the current study, potential therapeutic effects of these four polyphenols were evaluated in the transgenic APP/PS1 mouse model of cerebral amyloidosis. 5-months old transgenic mice were treated by Hesperidin, Icariin, Dihydromyricetin, Baicalin (100 mg/kg body weight) or vehicle by gavage, respectively. Therapeutic effects of these polyphenols were monitored by behavioral tests of nesting construction and social interaction. Then, the mice were sacrificed and tissues were taken for the pathological investigation. After a relatively short-term treatment of 10 days, Hesperidin and Icariin treatment significantly restored deficits in nesting ability, in comparison to age-, gender-, and bodyweight- matched transgenic littermates. The social interactive behavior was improved after treatment with Hesperidin. Immunohistological results indicated that Hesperidin and Icariin significantly attenuated β-amyloid deposition and microglial activation in both cortex and hippocampus of these transgenic mice. However, neither the behavioral dysfunction nor histopathological changes were improved after the treatment of Dihydromyricetin and Baicalin. Our findings suggest that Hesperidin and Icariin might be considered potential therapeutic candidates of human AD or even other neurodegenerative diseases.