Honokiol Ameliorates Amyloidosis and Neuroinflammation and Improves Cognitive Impairment in Alzheimer's Disease Transgenic Mice

The present study examined the effects of honokiol on amyloid- (A )-induced cognitive impairment and the underlying mechanisms in APPswe/PS1dE9 transgenic mice. The results showed that honokiol administration (20 mg/kg per day, intraperitoneally) for 6 weeks effectively improved spatial memory defic...

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Published in:The Journal of pharmacology and experimental therapeutics 2018-09, Vol.366 (3), p.470-478
Main Authors: Wang, Dongmei, Dong, Xiaohui, Wang, Chenying
Format: Article
Language:English
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Summary:The present study examined the effects of honokiol on amyloid- (A )-induced cognitive impairment and the underlying mechanisms in APPswe/PS1dE9 transgenic mice. The results showed that honokiol administration (20 mg/kg per day, intraperitoneally) for 6 weeks effectively improved spatial memory deficits in APPswe/PS1dE9 transgenic mice. Honokiol significantly lowered A production and senile plaque deposition by downregulating -site amyloid precursor protein cleavage enzyme 1 and enhancing A phagocytosis by microglia. Honokiol reduced glial cell activation and the production of proinflammatory cytokines (TNF- , IL-1 , and IL-6). Honokiol increased the transcriptional activity and protein levels of peroxisome proliferator-activated receptor- (PPAR However, all of the beneficial effects of honokiol on pathologic changes, including biochemistry and cognitive function, could be blocked by GW9662, a specific PPAR inhibitor. These findings suggested that honokiol may be a natural PPAR agonist, acting to attenuate A generation and neuroinflammation. Therefore, honokiol may be a potential therapeutic approach for Alzheimer's disease.
ISSN:0022-3565
1521-0103
DOI:10.1124/jpet.118.248674