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

Kenneth Kin Leung Kwan; Huang Yun; Tina Ting Xia Dong; Karl Wah Keung Tsim

doi:10.1016/j.jgr.2020.09.005

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

J Ginseng Res. 2021 Jul;45(4):473-481. doi: 10.1016/j.jgr.2020.09.005. Epub 2020 Oct 1.

Authors

Kenneth Kin Leung Kwan^{1

2}, Huang Yun^{1

2}, Tina Ting Xia Dong^{1

2}, Karl Wah Keung Tsim^{1

2}

Affiliations

¹ Shenzhen Key Laboratory of Edible and Medicinal Bioresources, Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen, China.
² Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

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: Alzheimer disease; Extracellular flux analyzer; Mitochondrial dynamics; Panax ginseng; ROS.