Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Notoginseng leaf triterpenes ameliorates mitochondrial oxidative injury via the NAMPT-SIRT1/2/3 signaling pathways in cerebral ischemic model rats

  • Weijie, Xie (Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences) ;
  • Ting, Zhu (Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences) ;
  • Ping, Zhou (Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences) ;
  • Huibo, Xu (Jilin Academy of Chinese Medicine) ;
  • Xiangbao, Meng (Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences) ;
  • Tao, Ding (Jilin Academy of Chinese Medicine) ;
  • Fengwei, Nan (Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences) ;
  • Guibo, Sun (Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences) ;
  • Xiaobo, Sun (Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences)
  • Received : 2020.05.09
  • Accepted : 2020.11.16
  • Published : 2023.03.02
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Abstract

Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.

Keywords

Acknowledgement

This work was supported by the National Natural Science Foundation of China (No. 81773938), the National Key Research and Development Project (No. 2017YFC1702504), the Key Laboratory Construction Project of Chinese Academy of Medical Sciences (No. 2018PT35030), the National Natural Science Foundation of China (No. 81891012), and the Clinical Research Project of Chinese Medicine "Qiye Tongmai Capsule" (No. 2015ZX09101020). We express our sincere gratitude to the foundations. In additions, it was appreciated that PNGL samples were provided by Jilin Academy of Chinese Medicine.

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