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The present study examined the effects of honokiol on amyloid- β (A β )-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 β production and senile plaque deposition by downregulating β -site amyloid precursor protein cleavage enzyme 1 and enhancing A β phagocytosis by microglia. Honokiol reduced glial cell activation and the production of proinflammatory cytokines (TNF- α , IL-1 β , and IL-6). Honokiol increased the transcriptional activity and protein levels of peroxisome proliferator-activated receptor- γ (PPAR γ) However, all of the beneficial effects of honokiol on pathologic changes, including biochemistry and cognitive function, could be blocked by GW9662, a specific PPAR γ inhibitor. These findings suggested that honokiol may be a natural PPAR γ agonist, acting to attenuate A β generation and neuroinflammation. Therefore, honokiol may be a potential therapeutic approach for Alzheimer's disease.

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