Effect of ginkgolide K on calcium channel activity in Alzheimer's disease

Liu,Hongbin; Li,Qinyun; Zhang,Xiaodan; Shi,Yun; Li,Jinyi

doi:10.3892/etm.2022.11353

Effect of ginkgolide K on calcium channel activity in Alzheimer's disease

Authors:
- Hongbin Liu
- Qinyun Li
- Xiaodan Zhang
- Yun Shi
- Jinyi Li
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Affiliations: No. 2 Department of Geriatrics, Beijing Geriatric Hospital, Beijing 100095, P.R. China, Dolu Health Consultant Co., Ltd., Tangshan, Hebei 063000, P.R. China
Published online on: May 5, 2022 https://doi.org/10.3892/etm.2022.11353
Article Number: 426
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative dementia with the key pathological hallmark of amyloid deposits that may induce mitochondrial dysfunction. Ginkgolide K (GK) has been proven to have neuroprotective effects. The present study sought to explore the neuroprotective effect of GK through regulation of the expression of mitochondrial Ca2+ uniporter (MCU) in the pathology of AD. SH‑SY5Y cells were cultured and the expression of MCU was enhanced by transfection of MCU recombinant vectors or knockdown by MCU small interfering RNA. The cells were treated with GK and amyloid β (Aβ). Thereafter, the effects of GK, MCU expression and Aβ on viability and apoptosis of SH‑SY5Y cells were examined via a WST‑1 assay, flow cytometry and Caspase‑3/8 activity assays, respectively. The effects of GK, MCU expression and Aβ on the calcium levels in mitochondria were also examined. The regulatory effect of GK on MCU expression was examined by reverse transcription‑quantitative PCR and western blot analysis. Furthermore, APP/PS1 mice received supplementation with GK and their cognitive ability was then examined through water maze tests, while the expression of MCU was examined using immunohistochemistry. The results indicated that enhancing the expression of MCU inhibited cell viability and promoted apoptosis. GK protected cells from amyloid‑induced cytotoxicity by promoting cell viability and preventing cell apoptosis. The neuroprotective effect of GK was abolished when MCU expression was knocked down. GK decreased the expression of MCU in vitro and downregulation of MCU decreased the calcium level in mitochondria. Treatment with GK in APP/PS1 mice downregulated the expression of MCU in the brains and alleviated cognitive impairment. In conclusion, the present study demonstrated that the administration of GK protected neurons by preventing apoptosis. Furthermore, the neuroprotective effect of GK in neuronal cells was indicated to be related to the inhibition of MCU expression. Therefore, administration of GK may be a promising strategy for treating AD.

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