2. Academic Validation
  3. Protective effects of Gypenoside XVII against cerebral ischemia/reperfusion injury via SIRT1-FOXO3A- and Hif1a-BNIP3-mediated mitochondrial autophagy

Protective effects of Gypenoside XVII against cerebral ischemia/reperfusion injury via SIRT1-FOXO3A- and Hif1a-BNIP3-mediated mitochondrial autophagy

  • J Transl Med. 2022 Dec 27;20(1):622. doi: 10.1186/s12967-022-03830-9.
Weijie Xie # 1 2 3 4,  Ting Zhu # 1 2 3 5,  Shuxia Zhang 1 2 3,  Xiaobo Sun 6 7 8
Affiliations

Affiliations

  • 1 Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100193, China.
  • 2 Key Laboratory of Material Basis and Resource Utilization of Chinese Herbal Medicine, Beijing, 100193, China.
  • 3 State Administration of Traditional Chinese Medicine Key Laboratory of Efficacy evaluation of Traditional Chinese Medicine in intervention of disorders of glucose and Lipid Metabolism, Beijing, 100193, China.
  • 4 Shanghai Mental Health Centre, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China.
  • 5 Institute of Neuroregeneration & Neurorehabilitation, Department of Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China.
  • 6 Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100193, China. sun-xiaobo@163.com.
  • 7 Key Laboratory of Material Basis and Resource Utilization of Chinese Herbal Medicine, Beijing, 100193, China. sun-xiaobo@163.com.
  • 8 State Administration of Traditional Chinese Medicine Key Laboratory of Efficacy evaluation of Traditional Chinese Medicine in intervention of disorders of glucose and Lipid Metabolism, Beijing, 100193, China. sun-xiaobo@163.com.
  • # Contributed equally.
PMID: 36572901 DOI: 10.1186/s12967-022-03830-9
Abstract

Background: Mitochondrial Autophagy maintains mitochondrial function and cellular homeostasis and plays a critical role in the pathological process of cerebral ischemia/reperfusion injury (CIRI). Whether Gypenoside XVII (GP17) has regulatory effects on mitochondrial Autophagy against CIRI remains unclear. The purpose of this study was to investigate the pharmacodynamic effects and mechanisms of GP17 on mitochondrial Autophagy after CIRI.

Methods: A rat middle cerebral artery occlusion/reperfusion (MCAO/R) model was used to assess the effects of GP17 against CIRI and to explore the underlying mechanisms. An oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was used to verify the ameliorative effects on mitochondrial damage and to probe the Autophagy pathways involved in combating neural injuries.

Results: The in vivo results showed that GP17 significantly improved mitochondrial metabolic functions and suppressed cerebral ischemic injury, possibly via the Autophagy pathway. Further research revealed that GP17 maintains moderate activation of Autophagy under ischemic and OGD conditions, producing neuroprotective effects against CIRI, and that the regulation of mitochondrial Autophagy is associated with crosstalk between the SIRT1-FOXO3A and Hif1a-BNIP3 signalling pathway that is partially eliminated by the specific inhibitors AGK-7 and 2-ME.

Conclusion: Overall, this work offers new insights into the mechanisms by which GP17 protects against CIRI and highlights the potential of therapy with Notoginseng leaf triterpene compounds as a novel clinical strategy in humans.

Keywords

BNIP3; Cerebral ischemia/reperfusion injury; FOXO3A; Gypenoside XVII; Mitochondrial autophagy.

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