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KMID : 0352720230470040561
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Journal of Ginseng Research
2023 Volume.47 No. 4 p.561 ~ p.571
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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
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Bao Trong Nguyen
Shin Eun-Joo
Jeong Ji-Hoon
Naveen Sharma
Ngoc Kim Cuong Tran
Yen Nhi Doan Nguyen
Kim Dae-Joong
Wie Myung-Bok
Lee Yi
Byun Jae-Kyung
Ko Sung-Kwon
Nah Seung-Yeol
Kim Hyoung-Chun
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Abstract
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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.
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KEYWORD
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mountain cultivated ginseng, aging-induced cognitive impairments, aged GPx-1 knockout mice, Nrf2/ChAT/ERK signaling cascade, hippocampus
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