Acknowledgement
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2020R1I1A3A04038150) and a grant (2020-2021) from the Korean Society of Ginseng.
References
- Salzer JL, Zalc B, Myelination. Curr Biol 2016;26:R971-5. https://doi.org/10.1016/j.cub.2016.07.074
- Xin W, Chan JR. Myelin plasticity: sculpting circuits in learning and memory. Nat Rev Neurosci 2020;21:682-94. https://doi.org/10.1038/s41583-020-00379-8
- Hill RA, Li AM, Grutzendler J. Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain. Nat Neurosci 2018;21:683-95. https://doi.org/10.1038/s41593-018-0120-6
- Dvorak AV, Swift-LaPointe T, Vavasour IM, LE Lee, Abel S, Russell-Schulz B, Graf C, Wurl A, Liu H, Laule C, et al. An atlas for human brain myelin content throughout the adult life span. Sci. Rep. 2021;11:269.
- Bouhrara M, Reiter DA, Bergeron CM, Zukley LM, Ferrucci L, Resnick SM, Spencer G. Evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content. Alzheimers Dement 2018;14:998-1004. https://doi.org/10.1016/j.jalz.2018.03.007
- Rahmanzadeh R, Lu PJ, Barakovic M, Weigel M, Maggi P, Nguyen TD, Schiavi S, Daducci A, Rosa FL, Schaedelin S, et al. Myelin and axon pathology in multiple sclerosis assessed by myelin water and multi-shell diffusion imaging. Brain 2021;144:1684-96. https://doi.org/10.1093/brain/awab088
- Hyun SH, Bhilare KD, , G In, Park CK, Kim JH. Effects of panax ginseng and ginsenosides on oxidative stress and cardiovascular diseases: pharmacological and therapeutic roles. J Ginseng Res 2022;46:33-8. https://doi.org/10.1016/j.jgr.2021.07.007
- Lee YY, Kim SD, Park SC, Rhee MH. Panax ginseng: inflammation, platelet aggregation, thrombus formation, and atherosclerosis crosstalk. J Ginseng Res 2022;46:54-61. https://doi.org/10.1016/j.jgr.2021.09.003
- Smith I, Williamson EM, Putnam S, Farrimond J, Whalley BJ. Effects and mechanisms of ginseng and ginsenosides on cognition. Nutr Rev 2014;72:319-33. https://doi.org/10.1111/nure.12099
- Dong L, Wang Y, Lv J, Zhang H, Jiang N, Lu C, Xu P, Liu X. Memory enhancement of fresh ginseng on deficits induced by chronic restraint stress in mice. Nutr. Neurosci. 2019;22:235-42. https://doi.org/10.1080/1028415x.2017.1373928
- Kim HJ, Jung SW, Kim SY, Cho IH, Kim HC, Rhim H, Kim M, Nah S. Panax ginseng as an adjuvant treatment for alzheimer's disease. J. Ginseng. Res. 2018;42:401-11. https://doi.org/10.1016/j.jgr.2017.12.008
- Nasrabady SE, Rizvi B, Goldman JE, Brickman AM. White matter changes in alzheimer's disease: a focus on myelin and oligodendrocytes. Acta Neuropathol Commun 2018;6:22.
- Lubetzki C, Zalc B, Williams A, Stadelmann C, Stankoff B. Remyelination in multiple sclerosis: from basic science to clinical translation. Lancet Neurol 2020;19:678-88. https://doi.org/10.1016/s1474-4422(20)30140-x
- Shin BK, Kwon SW, Park JH. Chemical diversity of ginseng saponins from panax ginseng. J Ginseng Res 2015;39:287-98. https://doi.org/10.1016/j.jgr.2014.12.005
- Han B, Park M, Han Y. Chemical and biochemical studies on non-saponin constituents of Korean ginseng. Journal of Ginseng Research 1992;16:228-34.
- Pyo M, Choi S, Hwang S, Shin T, Lee B, Lee S, Lim Y, Kim D, Nah S. Novel glycolipoproteins from ginseng. J. Ginseng. Res. 2011;35:92-103. https://doi.org/10.5142/jgr.2011.35.1.092
- Lee A, Kwon OW, Jung KR, Song GJ, Yang HJ. The effects of Korean red ginsengderived components on oligodendrocyte lineage cells: distinct facilitatory roles of the non-saponin and saponin fractions, and rb1, in proliferation, differentiation and myelination. J Ginseng Res 2022;46:104-14. https://doi.org/10.1016/j.jgr.2021.04.007
- Mijan MA, Kim JY, Moon SY, Choi SH, Nah SY, Yang HJ. Gintonin enhances proliferation, late stage differentiation, and cell survival from endoplasmic reticulum stress of oligodendrocyte lineage cells. Front Pharmacol 2019;10:1211.
- Ahmed T, Raza SH, Maryam A, Setzer WN, Braidy N, Nabavi SF, Oliveira MR, Nabavi SM. Ginsenoside rb1 as a neuroprotective agent: a review. Brain Res. Bull. 2016;125:30-43. https://doi.org/10.1016/j.brainresbull.2016.04.002
- Zhou P, Xie W, He S, Sun Y, Meng X, Sun G, Sun X. Ginsenoside rb1 as an antidiabetic agent and its underlying mechanism analysis. Cells 2019;8.
- Zhou P, Xie W, Sun Y, Dai Z, Li G, Sun G, Sun X. Ginsenoside rb1 and mitochondria: a short review of the literature. Mol. Cell Probes 2019;43:1-5. https://doi.org/10.1016/j.mcp.2018.12.001
- Chen Y, Li YY, Wang S, Zhou T, Chen NH, Yuan YH. Ginsenoside rg1 plays a neuroprotective role in regulating the iron-regulated proteins and against lipid peroxidation in oligodendrocytes. Neurochem Res 2022;47(6):1721-35. https://doi.org/10.1007/s11064-022-03564-6.
- Gudi V, Gingele S, Skripuletz T, Stangel M. Glial response during cuprizone-induced de- and remyelination in the cns: lessons learned. Front Cell Neurosci 2014;8:73.
- Faizi M, Salimi A, Seydi E, Naserzadeh P, Kouhnavard M, Rahimi A, Pourahmad J. Toxicity of cuprizone a cu(2+) chelating agent on isolated mouse brain mitochondria: a justification for demyelination and subsequent behavioral dysfunction. Toxicol. Mech. Methods 2016;26:276-83. https://doi.org/10.3109/15376516.2016.1172284
- Acs P, Kalman B. Pathogenesis of multiple sclerosis: what can we learn from the cuprizone model. Methods Mol Biol 2012;900:403-31. https://doi.org/10.1007/978-1-60761-720-4_20
- Acs P, Ma Selak, Komoly S, Kalman B. Distribution of oligodendrocyte loss and mitochondrial toxicity in the cuprizone-induced experimental demyelination model. J Neuroimmunol 2013;262:128-31. https://doi.org/10.1016/j.jneuroim.2013.06.012
- Kesterson JW, Carlton WW. Monoamine oxidase inhibition and the activity of other oxidative enzymes in the brains of mice fed cuprizone. Toxicol Appl Pharmacol 1971;20:386-95. https://doi.org/10.1016/0041-008X(71)90281-X
- Venturini G. Enzymic activities and sodium, potassium and copper concentrations in mouse brain and liver after cuprizone treatment in vivo. J Neurochem 1973;21:1147-51. https://doi.org/10.1111/j.1471-4159.1973.tb07569.x
- Benardais K, Kotsiari A, Skuljec J, Koutsoudaki PN, Gudi V, Singh V, Vulinovic F, Skripuletz T, Stangel M. Cuprizone [bis(cyclohexylidenehydrazide)] is selectively toxic for mature oligodendrocytes. Neurotox. Res. 2013;24:244-50. https://doi.org/10.1007/s12640-013-9380-9
- Neumann B, Baror R, Zhao C, Segel M, Dietmann S, Rawji KS, Foerster S, McClain CR, Chalut K, Wijngaarden P, et al. Metformin restores cns remyelination capacity by rejuvenating aged stem cells. Cell Stem Cell 2019;25:473-85. e8. https://doi.org/10.1016/j.stem.2019.08.015
- Schoenfeld R, Wong A, Silva J, Li M, Itoh A, Horiuchi M, Itoh T, Pleasure D, Cortopassi G. Oligodendroglial differentiation induces mitochondrial genes and inhibition of mitochondrial function represses oligodendroglial differentiation. Mitochondrion 2010;10:143-50. https://doi.org/10.1016/j.mito.2009.12.141
- Naughton MC, McMahon JM, FitzGerald U. Differential activation of er stress pathways in myelinating cerebellar tracts. Int J Dev Neurosci 2015;47:347-60. https://doi.org/10.1016/j.ijdevneu.2015.08.002
- Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interaction of bip and er stress transducers in the unfolded-protein response. Nat Cell Biol 2000;2:326-32. https://doi.org/10.1038/35014014
- Choy MS, Yusoff P, Lee IC, Newton JC, Goh CW, Page R, Shenolikar S, Peti W. Structural and functional analysis of the gadd34:Pp1 eif2alpha phosphatase. Cell Rep. 2015;11:1885-91. https://doi.org/10.1016/j.celrep.2015.05.043
- Li J, Inoue R, Togashi Y, Okuyama T, Satoh A, Kyohara M, Nishiyama K, Tsuno T, Miyashita D, Kin T, et al. Imeglimin ameliorates beta-cell apoptosis by modulating the endoplasmic reticulum homeostasis pathway. Diabetes 2022;71:424-39. https://doi.org/10.2337/db21-0123
- Fischbach F, Nedelcu J, Leopold P, Zhan J, Clarner T, Nellessen L, Beibel C, Heuvel Y, Goswami A, Weis J, et al. Cuprizone-induced graded oligodendrocyte vulnerability is regulated by the transcription factor DNA damageinducible transcript 3. Glia 2019;67:263-76. https://doi.org/10.1002/glia.23538
- Zheng QL, Zhu HY, Xu X, Chu SF, Cui LY, Dong YX, Liu Y, Zhan J, Wang Z, Chen N. Korean red ginseng alleviate depressive disorder by improving astrocyte gap junction function. J. Ethnopharmacol. 2021;281:114466.
- Lee MJ, Jang M, Choi J, Chang BS, Kim DY, Kim SH, Kwak Y, Oh S, Lee J, Chang B, et al. Korean red ginseng and ginsenoside-rb1/-rg1 alleviate experimental autoimmune encephalomyelitis by suppressing th1 and th17 cells and upregulating regulatory t cells. Mol. Neurobiol. 2016;53:1977-2002. https://doi.org/10.1007/s12035-015-9131-4
- Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 2013;53:401-26. https://doi.org/10.1146/annurev-pharmtox-011112-140320
- Ishibashi T, Dakin KA, Stevens B, Lee PR, Kozlov SV, Stewart CL, Fields RD. Astrocytes promote myelination in response to electrical impulses. Neuron 2006;49:823-32. https://doi.org/10.1016/j.neuron.2006.02.006
- Dong YX, Chu SF, Wang SS, Tian YJ, He WB, Du YS, Wang Z, Yan X, Zhang Z, Chen N. Rg1 exerts protective effect in cpz-induced demyelination mouse model via inhibiting cxcl10-mediated glial response. Acta Pharmacol. Sin. 2022;43:563-76. https://doi.org/10.1038/s41401-021-00696-3
- Powers BE, Sellers DL, Lovelett EA, Cheung W, Aalami SP, Zapertov N, Maris DO, Horner PJ. Remyelination reporter reveals prolonged refinement of spontaneously regenerated myelin. Proc. Natl. Acad. Sci. U.S.A. 2013;110:4075-80. https://doi.org/10.1073/pnas.1210293110
- Najm FJ, Lager AM, Zaremba A, Wyatt K, Caprariello AV, Factor DC, Karl RT, Maeda T, Miler RH, Tesar PJ. Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells. Nat. Biotechnol. 2013;31:426-33. https://doi.org/10.1038/nbt.2561
- Groves AK, Barnett SC, Franklin RJ, Crang AJ, Mayer M, Blakemore WF, Noble M. Repair of demyelinated lesions by transplantation of purified o-2a progenitor cells. Nature 1993;362:453-5. https://doi.org/10.1038/362453a0
- Windrem MS, Nunes MC, Rashbaum WK, Schwartz TH, Goodman RA, McKhann 2nd G, Roy NS, Goldman SA. Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nat. Med. 2004;10:93-7. https://doi.org/10.1038/nm974
- Bujalka H, Koenning M, Jackson S, Perreau VM, Pope B, Hay CM, Mitew S, Hill AF, Lu QR, Wegner M, et al. Myrf is a membrane-associated transcription factor that autoproteolytically cleaves to directly activate myelin genes. PLoS Biol. 2013;11:e1001625.
- Pajares M, Cuadrado A, Rojo AI. Modulation of proteostasis by transcription factor nrf2 and impact in neurodegenerative diseases. Redox Biol 2017;11: 543-53. https://doi.org/10.1016/j.redox.2017.01.006
- Cubillos-Ruiz JR, Bettigole SE, Glimcher LH. Tumorigenic and immunosuppressive effects of endoplasmic reticulum stress in cancer. Cell 2017;168:692-706. https://doi.org/10.1016/j.cell.2016.12.004
- Domingues HS, Portugal CC, Socodato R, Relvas JB. Oligodendrocyte, astrocyte, and microglia crosstalk in myelin development, damage, and repair. Front Cell Dev Biol 2016;4:71.
- Traiffort E, Kassoussi A, Zahaf A, Laouarem Y. Astrocytes and microglia as major players of myelin production in normal and pathological conditions. Front Cell Neurosci 2020;14:79.
- Luo JF, Shen XY, Lio CK, Dai Y, Cheng CS, Liu JX, Yao Y, Yu Y, Xie Y, Luo P, et al. Activation of nrf2/ho-1 pathway by nardochinoid c inhibits inflammation and oxidative stress in lipopolysaccharide-stimulated macrophages. Front Pharmacol. 2018;9:911.
- Skripuletz T, Hackstette D, Bauer K, Gudi V, Pul R, Voss E, Berger K, Kipp M, Baumgartner W, Stangel M. Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain 2013;136:147-67. https://doi.org/10.1093/brain/aws262
- Lloyd AF, Davies CL, Miron VE. Microglia: origins, homeostasis, and roles in myelin repair. Curr Opin Neurobiol 2017;47:113-20. https://doi.org/10.1016/j.conb.2017.10.001
- Lee MJ, Chang BJ, Oh S, Nah SY, Cho IH. Korean red ginseng mitigates spinal demyelination in a model of acute multiple sclerosis by downregulating p38 mitogen-activated protein kinase and nuclear factor-kappab signaling pathways. J Ginseng Res 2018;42:436-46. https://doi.org/10.1016/j.jgr.2017.04.013