title: EGb761 improves cognitive function and regulates inflammatory responses in the APP/PS1 mouse.
abstract: There is accumulating evidence that the Ginkgo biloba extract EGb761 may help to prevent Alzheimer's disease (AD). However, the underlying mechanism of its action remains to be elaborated. In this study, we examined the effects of EGb761 using the APP/PS1 transgenic mouse model of AD. Two-month-old APP/PS1 mice were supplemented with EGb761 daily for 6months. We found that this chronic treatment with EGb761 improved the cognitive function of these mice and also significantly alleviated amyloid plaque deposition. Although the level of insoluble amyloid beta (Aβ) was decreased, the soluble content of Aβ was not changed after administration of EGb761. We then determined the changes in central inflammation and observed that the activated microglia around amyloid plaque was increased in these treated mice. We also found that chronic EGb761 treatment downregulated pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS), and upregulated anti-inflammatory cytokines and Arginase-1 (Arg-1), suggesting that EGb761 regulated the phenotype of activated microglia in the APP/PS1 mouse brain. In support of this, pretreatment of the BV2 microglial cell line with EGb761 inhibited the inflammatory reaction to Aβ. Furthermore, the addition of conditioned media derived from BV2 cells that were co-treated with Aβ and EGb761, protected neurons against treatment of Aβ and inhibited apoptotic damage. Taken together, our results demonstrated that EGb761 provided a protective effect in APP/PS1 mouse. This protection was correlated with an inhibition of the pro-inflammatory effects of microglia and an induction of anti-inflammatory effects. These results strongly suggest that EGb761 provides a protective effect in APP/PS1 mouse via regulation of inflammation in the brain.
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wan
authors.affiliation: Department of Chinese Medicine, Dongfang Hospital, Tongji University, Shanghai, PR China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington D.C., USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Danielsen
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington D.C., USA.
authors.forename: Qianlei
authors.initials: Q
authors.lastname: Li
authors.affiliation: Geriatrics Department of Chinese Medicine & Shanghai Key Laboratory of Clinical Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Chen
authors.affiliation: Geriatrics Department of Chinese Medicine & Shanghai Key Laboratory of Clinical Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, PR China.
authors.forename: Yuanjin
authors.initials: Y
authors.lastname: Chan
authors.affiliation: Geriatrics Department of Chinese Medicine & Shanghai Key Laboratory of Clinical Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, PR China. Electronic address: doctorymli@163.com.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020441:Ginkgo biloba; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000517:prevention & control; D000096983:Ginkgo Extract
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C496317:Nos2 protein, mouse
keywords: Alzheimer's disease; Amyloid beta; EGb761; Microglia; Neuroinflammation