PT - JOURNAL ARTICLE AU - Dongmei Wang AU - Xiaohui Dong AU - Chenying Wang TI - Honokiol Ameliorates Amyloidosis and Neuroinflammation and Improves Cognitive Impairment in Alzheimer’s Disease Transgenic Mice AID - 10.1124/jpet.118.248674 DP - 2018 Sep 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 470--478 VI - 366 IP - 3 4099 - http://jpet.aspetjournals.org/content/366/3/470.short 4100 - http://jpet.aspetjournals.org/content/366/3/470.full SO - J Pharmacol Exp Ther2018 Sep 01; 366 AB - The present study examined the effects of honokiol on amyloid-β (Aβ)-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 Aβ production and senile plaque deposition by downregulating β-site amyloid precursor protein cleavage enzyme 1 and enhancing Aβ phagocytosis by microglia. Honokiol reduced glial cell activation and the production of proinflammatory cytokines (TNF-α, IL-1β, and IL-6). Honokiol increased the transcriptional activity and protein levels of peroxisome proliferator-activated receptor-γ (PPARγ). However, all of the beneficial effects of honokiol on pathologic changes, including biochemistry and cognitive function, could be blocked by GW9662, a specific PPARγ inhibitor. These findings suggested that honokiol may be a natural PPARγ agonist, acting to attenuate Aβ generation and neuroinflammation. Therefore, honokiol may be a potential therapeutic approach for Alzheimer’s disease.