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Ginsenosides attenuate bioenergetics and morphology of mitochondria in cultured PC12 cells under the insult of amyloid beta-peptide

  • Kwan, Kenneth Kin Leung (Shenzhen Key Laboratory of Edible and Medicinal Bioresources, Shenzhen Research Institute) ;
  • Yun, Huang (Shenzhen Key Laboratory of Edible and Medicinal Bioresources, Shenzhen Research Institute) ;
  • Dong, Tina Ting Xia (Shenzhen Key Laboratory of Edible and Medicinal Bioresources, Shenzhen Research Institute) ;
  • Tsim, Karl Wah Keung (Shenzhen Key Laboratory of Edible and Medicinal Bioresources, Shenzhen Research Institute)
  • Received : 2020.07.04
  • Accepted : 2020.09.21
  • Published : 2021.07.01

Abstract

Background: Mitochondrial dysfunction is one of the significant reasons for Alzheimer's disease (AD). Ginsenosides, natural molecules extracted from Panax ginseng, have been demonstrated to exert essential neuroprotective functions, which can ascribe to its anti-oxidative effect, enhancing central metabolism and improving mitochondrial function. However, a comprehensive analysis of cellular mitochondrial bioenergetics after ginsenoside treatment under Aβ-oxidative stress is missing. Methods: The antioxidant activities of ginsenoside Rb1, Rd, Re, Rg1 were compared by measuring the cell survival and reactive oxygen species (ROS) formation. Next, the protective effects of ginsenosides of mitochondrial bioenergetics were examined by measuring oxygen consumption rate (OCR) in PC12 cells under Aβ-oxidative stress with an extracellular flux analyzer. Meanwhile, mitochondrial membrane potential (MMP) and mitochondrial dynamics were evaluated by confocal laser scanning microscopy. Results: Ginsenoside Rg1 possessed the strongest anti-oxidative property, and which therefore provided the best protective function to PC12 cells under the Aβ oxidative stress by increasing ATP production to 3 folds, spare capacity to 2 folds, maximal respiration to 2 folds and non-mitochondrial respiration to 1.5 folds, as compared to Aβ cell model. Furthermore, ginsenoside Rg1 enhanced MMP and mitochondrial interconnectivity, and simultaneously reduced mitochondrial circularity. Conclusion: In the present study, these results demonstrated that ginsenoside Rg1 could be the best natural compound, as compared with other ginsenosides, by modulating the OCR of cultured PC12 cells during oxidative phosphorylation, in regulating MMP and in improving mitochondria dynamics under Aβ-induced oxidative stress.

Keywords

Acknowledgement

This work is supported by GBA Institute of Collaborate Innovation (GICI-022); Special project of Foshan University of science and technology in 2019 (FSUST19-SRI10); Shenzhen Science and Technology Innovation Committee (ZDSYS201707281432317; JCYJ20170413173747440; JCYJ20180306174903174), Zhongshan Municipal Bureau of Science and Technology (ZSST20SC03); Guangzhou Science and Technology Committee Research Grant (GZSTI16SC02; GZSTI17SC02); Hong Kong RGC Theme-based Research Scheme (T13-605/18-W); Hong Kong Innovation Technology Fund (UIM/340, UIM/385, ITS/500/18FP; TUYF19SC02; PD18SC01 and HMRF18SC06).

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