Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rg1 ameliorates Alzheimer's disease pathology via restoring mitophagy

  • Ni Wang (Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University) ;
  • Junyan Yang (Department of Clinical Laboratory, Stomatological Hospital, Chongqing Medical University) ;
  • Ruijun Chen (School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong) ;
  • Yunyun Liu (Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University) ;
  • Shunjie Liu (Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University) ;
  • Yining Pan (School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong) ;
  • Qingfeng Lei (Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University) ;
  • Yuzhou Wang (Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University) ;
  • Lu He (Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University) ;
  • Youqiang Song (School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong) ;
  • Zhong Li (Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University)
  • Received : 2022.05.11
  • Accepted : 2022.12.12
  • Published : 2023.05.01
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Abstract

Background: Alzheimer's disease (AD) is a common form of dementia, and impaired mitophagy is a hallmark of AD. Mitophagy is mitochondrial-specific autophagy. Ginsenosides from Ginseng involve in autophagy in cancer. Ginsenoside Rg1 (Rg1 hereafter), a single compound of Ginseng, has neuroprotective effects on AD. However, few studies have reported whether Rg1 can ameliorate AD pathology by regulating mitophagy. Methods: Human SH-SY5Y cell and a 5XFAD mouse model were used to investigate the effects of Rg1. Rg1 (1µM) was added to β-amyloid oligomer (AβO)-induced or APPswe-overexpressed cell models for 24 hours. 5XFAD mouse models were intraperitoneally injected with Rg1 (10 mg/kg/d) for 30 days. Expression levels of mitophagy-related markers were analyzed by western blot and immunofluorescent staining. Cognitive function was assessed by Morris water maze. Mitophagic events were observed using transmission electron microscopy, western blot, and immunofluorescent staining from mouse hippocampus. The activation of the PINK1/Parkin pathway was examined using an immunoprecipitation assay. Results: Rg1 could restore mitophagy and ameliorate memory deficits in the AD cellular and/or mouse model through the PINK1-Parkin pathway. Moreover, Rg1 might induce microglial phagocytosis to reduce β-amyloid (Aβ) deposits in the hippocampus of AD mice. Conclusion: Our studies demonstrate the neuroprotective mechanism of ginsenoside Rg1 in AD models. Rg1 induces PINK-Parkin mediated mitophagy and ameliorates memory deficits in 5XFAD mouse models.

Keywords

Acknowledgement

We thank all members of Dr. Gao Bo's lab (The University of Hong Kong) for supporting experimental materials. We thank Dr. Ling Li, Mr. Md. Farhad Hossain, and Miss Hongting Xu for discussing and editing this paper.

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