2. Academic Validation
  3. Compound K inhibits autophagy-mediated apoptosis induced by oxygen and glucose deprivation/reperfusion via regulating AMPK-mTOR pathway in neurons

Compound K inhibits autophagy-mediated apoptosis induced by oxygen and glucose deprivation/reperfusion via regulating AMPK-mTOR pathway in neurons

  • Life Sci. 2020 Aug 1;254:117793. doi: 10.1016/j.lfs.2020.117793.
Qingxia Huang 1,  Tingting Lou 1,  Manying Wang 1,  Linyuan Xue 2,  Jing Lu 2,  He Zhang 2,  Zepeng Zhang 2,  Hui Wang 2,  Chenxu Jing 2,  Daqing Zhao 3,  Liwei Sun 4,  Xiangyan Li 5
Affiliations

Affiliations

  • 1 Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, China; Research Center of Traditional Chinese Medicine, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China.
  • 2 Research Center of Traditional Chinese Medicine, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China.
  • 3 Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, China; Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun, Jilin, China; Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, China.
  • 4 Research Center of Traditional Chinese Medicine, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China; Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun, Jilin, China. Electronic address: sunnylilwei@163.com.
  • 5 Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, China; Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun, Jilin, China; Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, China. Electronic address: xiangyan_li1981@163.com.
PMID: 32416164 DOI: 10.1016/j.lfs.2020.117793
Abstract

Aims: Oxygen and glucose deprivation and reperfusion (OGD/R) injury contributes to the pathophysiology after ischemic stroke, which needs to urgently develop treatment strategies. Previous studies have demonstrated that Autophagy in reperfusion period exerted adverse effects on the cerebral ischemic injury. Ginsenoside monomer compound K (CK) is the main intestinal metabolite of ginseng that exerts the pharmacological activities and has a protective effect against cerebral OGD/R injury. However, the specific molecular mechanism of CK protects against OGD/R injury in neurons is still unclear.

Materials and methods: In this study, cell viability, Reactive Oxygen Species (ROS) generation, CA2+ overload, mitochondrial membrane potential depolarization, Autophagy and Apoptosis were investigated in OGD/R-induced neuronal cells injury after pretreatment with CK and in combination with BML-275 or rapamycin.

Key findings: Our study found that pretreatment with CK protected neurons against OGD/R injury by increasing cell viability and decreasing the ROS generation, mitochondrial damage, and CA2+ overload. Moreover, CK cut down autophagy-mediated Apoptosis via promoting the process of forming autophagosomes into phagocytic precursors. Furthermore, our study clarified the neuroprotective of CK against OGD/R-induced neural Autophagy and Apoptosis through the regulation of the AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathway.

Significance: Taken together, our study provides credible experimental evidence and explains the potential molecular mechanism of CK as one of the main bioactive ingredients of ginseng for the treatment of cerebral ischemia/reperfusion injury.

Keywords

AMPK-mTOR pathway; Autophagy; Compound K; Neuron; Oxygen and glucose deprivation/reperfusion.

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