TY - JOUR T1 - Honokiol Ameliorates Amyloidosis and Neuroinflammation and Improves Cognitive Impairment in Alzheimer’s Disease Transgenic Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 470 LP - 478 DO - 10.1124/jpet.118.248674 VL - 366 IS - 3 AU - Dongmei Wang AU - Xiaohui Dong AU - Chenying Wang Y1 - 2018/09/01 UR - http://jpet.aspetjournals.org/content/366/3/470.abstract N2 - 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. ER -