Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury due to inhibition of NOX2-mediated calcium homeostasis dysregulation in mice

  • Han, Yuli (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Li, Xuewang (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Yang, Liu (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Zhang, Duoduo (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Li, Lan (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Dong, Xianan (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Li, Yan (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University) ;
  • Qun, Sen (Stroke Center & Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China) ;
  • Li, Weizu (Department of Pharmacology, Basic Medicine College, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University)
  • Received : 2021.05.08
  • Accepted : 2021.08.03
  • Published : 2022.07.01
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Abstract

Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca2+]i. The open-field test and poleclimbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca2+]i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

Keywords

Acknowledgement

The study is upheld by the Major projects of Anhui Provincial Department of Education (KJ2020ZD14) and the Key Research and Development Project of Anhui Province (202004j07020014) and the Hefei Science and Technology Bureau "Borrow, Transfer and Supplement" Project (J2019Y01).

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