Research Paper Volume 15, Issue 19 pp 10237—10252

Ginkgolide attenuates memory impairment and neuroinflammation by suppressing the NLRP3/caspase-1 pathway in Alzheimer’s disease

Guang-Zhi Liu1, , Tian-Tong Niu1, , Qian Yu2, , Bao-Lei Xu3, , Xiao-Qing Li1, , Bo-Yi Yuan1, , Guo-Bin Yuan1, , Ting-Ting Yang1, , Hui-Qin Li4, , Yi Sun4, ,

  • 1 Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
  • 2 Beijing D.A. Medical Laboratory, Beijing 102600, China
  • 3 National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
  • 4 Research and Development Centre, Chengdu Baiyu Pharmaceutical Co., Ltd., Chengdu 611130, China

Received: April 3, 2023       Accepted: July 17, 2023       Published: October 3, 2023
How to Cite

Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer’s disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aβ analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aβ1–42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1β and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1β, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aβ1–42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.


AChEIs: acetylcholinesterase inhibitors; AD: Alzheimer’s disease; APP: amyloid precursor protein; ASC: apoptosis-associated speck-like protein containing a CARD; ECL: electrochemiluminescence; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; H&E: hematoxylin and eosin; HRP: horseradish peroxidase; IL: interleukin; NF-κB: nuclear factor kappa B; NLRP3: nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3; PS1: presenilin 1; qRT-PCR: quantitative reverse transcription polymerase chain reaction; RIPA: radioimmunoprecipitation assay; ROS: reactive oxygen species; SDS: sodium dodecyl sulfate; WT: wild-type.