Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Mountain-cultivated ginseng protects against cognitive impairments in aged GPx-1 knockout mice via activation of Nrf2/ChAT/ERK signaling pathway

  • Bao Trong Nguyen (Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University) ;
  • Eun-Joo Shin (Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University) ;
  • Ji Hoon Jeong (Department of Global Innovative Drugs, Graduate School of Chung-Ang University, College of Medicine, Chung-Ang University) ;
  • Naveen Sharma (Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University) ;
  • Ngoc Kim Cuong Tran (Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University) ;
  • Yen Nhi Doan Nguyen (Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University) ;
  • Dae-Joong Kim (Department of Anatomy and Cell Biology, Medical School, Kangwon National University) ;
  • Myung Bok Wie (Department of Veterinary Toxicology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Yi Lee (Department of Industrial Plant Science & Technology, Chungbuk National University) ;
  • Jae Kyung Byun (Korea Society of Forest Environmental Research) ;
  • Sung Kwon Ko (Department of Oriental Medical Food & Nutrition, Semyung University) ;
  • Seung-Yeol Nah (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Hyoung-Chun Kim (Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University)
  • Received : 2022.06.13
  • Accepted : 2023.01.15
  • Published : 2023.07.01
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Abstract

Background: Escalating evidence shows that ginseng possesses an antiaging potential with cognitive enhancing activity. As mountain cultivated ginseng (MCG) is cultivated without agricultural chemicals, MCG has emerged as a popular herb medicine. However, little is known about the MCG-mediated pharmacological mechanism on brain aging. Methods: As we demonstrated that glutathione peroxidase (GPx) is important for enhancing memory function in the animal model of aging, we investigated the role of MCG as a GPx inducer using GPx-1 (a major type of GPx) knockout (KO) mice. We assessed whether MCG modulates redox and cholinergic parameters, and memory function in aged GPx-1 knockout KOmice. Results: Redox burden of aged GPx-1 KO mice was more evident than that of aged wild-type (WT) mice. Alteration of Nrf2 DNA binding activity appeared to be more evident than that of NFκB DNA binding activity in aged GPx-1 KO mice. Alteration in choline acetyltransferase (ChAT) activity was more evident than that in acetylcholine esterase activity. MCG significantly attenuated reductions in Nrf2 system and ChAT level. MCG significantly enhanced the co-localization of Nrf2-immunoreactivity and ChAT-immunoreactivity in the same cell population. Nrf2 inhibitor brusatol significantly counteracted MCG-mediated up-regulation in ChAT level and ChAT inhibition (by k252a) significantly reduced ERK phosphorylation by MCG, suggesting that MCG might require signal cascade of Nrf2/ChAT/ERK to enhance cognition. Conclusion: GPx-1 depletion might be a prerequisite for cognitive impairment in aged animals. MCG-mediated cognition enhancement might be associated with the activations of Nrf2, ChAT, and ERK signaling cascade.

Keywords

Acknowledgement

Naveen Sharma was supported by the BK21 program.

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