EGb761 improves cognitive function and regulates inflammatory responses in the APP/PS1 mouse

Exp Gerontol. 2016 Aug:81:92-100. doi: 10.1016/j.exger.2016.05.007. Epub 2016 May 22.


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.

Keywords: Alzheimer's disease; Amyloid beta; EGb761; Microglia; Neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Cognition / drug effects*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Ginkgo biloba
  • Male
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / pharmacology*
  • Plaque, Amyloid / prevention & control


  • Amyloid beta-Peptides
  • Cytokines
  • Plant Extracts
  • Ginkgo biloba extract
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse