Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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High fat diet-induced brain damaging effects through autophagy-mediated senescence, inflammation and apoptosis mitigated by ginsenoside F1-enhanced mixture

  • Hou, Jingang (Kaist Institute for BioCentury, KAIST) ;
  • Jeon, Byeongmin (Department of Biological Sciences, KAIST) ;
  • Baek, Jongin (Department of Biological Sciences, KAIST) ;
  • Yun, Yeejin (Department of Biological Sciences, KAIST) ;
  • Kim, Daeun (Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University) ;
  • Chang, Boyoon (Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University) ;
  • Kim, Sungyeon (Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University) ;
  • Kim, Sunchang (Kaist Institute for BioCentury, KAIST)
  • Received : 2020.10.13
  • Accepted : 2021.04.11
  • Published : 2022.01.01
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Abstract

Background: Herbal medicines are popular approaches to capably prevent and treat obesity and its related diseases. Excessive exposure to dietary lipids causes oxidative stress and inflammation, which possibly induces cellular senescence and contribute the damaging effects in brain. The potential roles of selective enhanced ginsenoside in regulating high fat diet (HFD)-induced brain damage remain unknown. Methods: The protection function of Ginsenoside F1-enhanced mixture (SGB121) was evaluated by in vivo and in vitro experiments. Human primary astrocytes and SH-SY5Y cells were treated with palmitic acid conjugated Bovine Serum Albumin, and the effects of SGB121 were determined by MTT and lipid uptake assays. For in vivo tests, C57BL/6J mice were fed with high fat diet for 3 months with or without SGB121 administration. Thereafter, immunohistochemistry, western blot, PCR and ELISA assays were conducted with brain tissues. Results and conclusion: SGB121 selectively suppressed HFD-induced oxidative stress and cellular senescence in brain, and reduced subsequent inflammation responses manifested by abrogated secretion of IL-6, IL-1β and TNFα via NF-κB signaling pathway. Interestingly, SGB121 protects against HFD-induced damage by improving mitophagy and endoplasmic reticulum-stress associated autophagy flux and inhibiting apoptosis. In addition, SGB121 regulates lipid uptake and accumulation by FATP4 and PPARα. SGB121 significantly abates excessively phosphorylated tau protein in the cortex and GFAP activation in corpus callosum. Together, our results suggest that SGB121 is able to favor the resistance of brain to HFD-induced damage, therefore provide explicit evidence of the potential to be a functional food.

Keywords

Acknowledgement

This work was supported by the Intelligent Synthetic Biology Center of the Global Frontier Project, funded by the Ministry of Education, Science and Technology (2011-0031955), Republic of Korea. Bio-Synergy Research Project (NRF-2021M3A9C4001028) of the Ministry of Science, ICT, Republic of Korea.

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