Journal of Ginseng Research

  • 제48권3호
  • /
  • Pages.245-252
  • /
  • 2024
  • /
  • 1226-8453(pISSN)
  • /
  • 2093-4947(eISSN)
고려인삼학회 (The Korean Society of Ginseng)
권호 표지
DOI QR코드

DOI QR Code

Emerging evidence that ginseng components improve cognition in subjective memory impairment, mild cognitive impairment, and early Alzheimer's disease dementia

  • Rami Lee (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Ji-Hun Kim (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Won-Woo Kim (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Sung-Hee Hwang (Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University) ;
  • Sun-Hye Choi (Department of Animal Health, College of Health and Medical Services, Osan University) ;
  • Jong-Hoon Kim (College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University) ;
  • Ik-Hyun Cho (Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University) ;
  • Manho Kim (Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Seung-Yeol Nah (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University)
  • 투고 : 2023.09.03
  • 심사 : 2024.02.15
  • 발행 : 2024.05.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Ginseng is a traditional herbal medicine used for prevention and treatment of various diseases as a tonic. Recent scientific cohort studies on life prolongation with ginseng consumption support this record, as those who consumed ginseng for more than 5 years had reduced mortality and cognitive decline compared to those who did not. Clinical studies have also shown that acute or long-term intake of ginseng total extract improves acute working memory performance or cognitive function in healthy individuals and those with subjective memory impairment (SMI), mild cognitive impairment (MCI), or early Alzheimer's disease (AD) dementia who are taking AD medication(s). Ginseng contains various components ranging from classical ginsenosides and polysaccharides to more recently described gintonin. However, it is unclear which ginseng component(s) might be the main candidate that contribute to memory or cognitive improvements or prevent cognitive decline in older individuals. This review describes recent clinical contributors to ginseng components in clinical tests and introduces emerging evidence that ginseng components could be novel candidates for cognitive improvement in older individuals, as ginseng components improve SMI cognition and exhibits add-on effects when coadministered with early AD dementia drugs. The mechanism behind the beneficial effects of ginseng components and how it improves cognition are presented. Additionally, this review shows how ginseng components can contribute to SMI, MCI, or early AD dementia when used as a supplementary food and/or medicine, and proposes a novel combination therapy of current AD medicines with ginseng component(s).

키워드

과제정보

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2023R1A2C1003481) awarded to S. Y. Nah.

참고문헌

  1. What is the dongui bogam? Korean Culture and Information Service (KOCIS);2014-04-29.
  2. Choi SH, Lee R, Nam SM, Kim DG, Cho IH, Kim HC, Cho Y, Rhim H, Nah SY. Ginseng gintonin, aging societies, and geriatric brain diseases. Integr Med Res 2021;10:100450.
  3. Lee J, Kwon S, Jin C, Cho SY, Park SU, Jung WS, Moon SK, Park JM, Ko CN, Cho KH. Traditional east asian herbal medicine treatment for Alzheimer's disease: a systematic review and meta-analysis. Pharmaceuticals 2022;15:174.
  4. Jung SH, Kim HR, Chun MY, Jang H, Cho M, Kim B, Kim S, Jeong JH, Yoon SJ, Park KW, et al. Transferability of alzheimer disease polygenic risk score across populations and its association with alzheimer disease-related phenotypes. JAMA Netw Open 2022;5:e2247162.
  5. Baek MS, Kim HK, Han K, Kwon HS, Na HK, Lyoo CH, Cho H. Annual trends in the incidence and prevalence of Alzheimer's disease in South Korea: a nationwide cohort study. Front Neurol 2022;13:883549.
  6. Lee DW, Seong SJ. Korean national dementia plans: from 1st to 3rd. J Korean Med Assoc 2018;61:298-303.
  7. Galvin JE, Aisen P, Langbaum JB, Rodriguez E, Sabbagh M, Stefanacci R, Stern RA, Vassey EA, de Wilde A, West N, et al. Early stages of alzheimer's disease: evolving the care team for optimal patient management. Front Neurol 2021;11:592302.
  8. Hampel H, Hardy J, Blennow K, Chen C, Perry G, Kim SH, Villemagne VL, Aisen P, Vendruscolo M, Iwatsubo T, et al. The amyloid-β pathway in Alzheimer's disease. Mol Psychiatr 2021;26:5481-503. https://doi.org/10.1038/s41380-021-01249-0
  9. Li J, Huang Q, Chen J, Qi H, Liu J, Chen Z, Zhao D, Wang Z, Li X. Neuroprotective potentials of panax ginseng against Alzheimer's Disease: a review of preclinical and clinal evidences. Front Pharmacol 2021;12:1-15.
  10. Siddiqui AJ, Badraoui R, Jahan S, Alshahrani MM, Siddiqui MA, Khan A, Adnan M. Targeting NMDA receptor in Alzheimer's disease: identifying novel inhibitors using computational approaches. Front Pharmacol 2023;21:1208968.
  11. Burns A. Diagnosis and management of Alzheimer's disease. Dialogues Clin Neurosci 2000;2:129-38. https://doi.org/10.31887/DCNS.2000.2.2/aburns
  12. DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer's disease. Mol Neurodegener 2019;14:32.
  13. Jack Jr CR, Knopman DS, Weigand SD, Wiste HJ, Vemuri P, Lowe V, Kantarci K, Gunter JL, Senjem ML, Ivnik RJ, et al. An operational approach to national institute on aging-Alzheimer's association criteria for preclinical Alzheimer disease. Ann Neurol 2012;71:765-75.
  14. Yi SW, Sull JW, Hong JS, Linton JA, Ohrr H. Association between ginseng intake and mortality: Kangwha cohort study. J Alternative Compl Med 2009;15:921-8. https://doi.org/10.1089/acm.2008.0296
  15. Pradhan P, Wen W, Cai H, Gao YT, Yang G, Shu XO, Zheng W. Association of ginseng consumption with all-cause and cause-specific mortality: Shanghai women's health study. J Epidemiol 2022;32:469-75. https://doi.org/10.2188/jea.JE20210393
  16. Lho SK, Kim TH, Kwak KP, Kim K, Kim BJ, Kim SG, Kim JL, Kim TH, Moon SW, Park JY, et al. Effects of lifetime cumulative ginseng intake on cognitive function in late life. Alzheimer's Res Ther 2018;10:50.
  17. Lee BC, Choe YM, Suh GH, Choi IG, Kim HS, Hwang J, Yi D, Jhoo JH, Kim JW. Ginseng intake and Alzheimer disease-specific cognition in older adults according to apolipoprotein ε4 allele status. Front Aging Neurosci 2023;15:1152626.
  18. Yamazaki Y, Zhao N, Caulfield TR, Liu CC, Bu G. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat Rev Neurol 2019;15:501-18. https://doi.org/10.1038/s41582-019-0228-7
  19. Malik M, Tlustos P. Nootropic herbs, shrubs, and trees as potential cognitive enhancers. Plants 2023;12:1364.
  20. Reay JL, Scholey AB, Kennedy DO. Panax ginseng (G115) improves aspects of working memory performance and subjective ratings of calmness in healthy young adults. Hum Psychopharmacol 2010;25:462-71. https://doi.org/10.1002/hup.1138
  21. Reay JL, Kennedy DO, Scholey AB. Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity. J Psychopharmacol 2005;19:357-65. https://doi.org/10.1177/0269881105053286
  22. Scholey AB, Kennedy DO. Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand. Hum Psychopharmacol 2002;17:35-44. https://doi.org/10.1002/hup.352
  23. Lee WJ, Shin YW, Chang H, Shin HR, Kim WW, Jung SW, Kim M, Nah SY. Safety and efficacy of dietary supplement (gintonin-enriched fraction from ginseng) in subjective memory impairment: a randomized placebo-controlled trial. Integr Med Res 2022;11:100773.
  24. Lee R, Lee H, Kim WW, Kim MH, Nah SY. Cognitive function improvement effects of gintonin enriched fraction in subjective memory impairment: an assessor-and participant-blinded placebo controlled study. J Ginseng Res 2023;47:735-42. https://doi.org/10.1016/j.jgr.2023.06.005
  25. Park KC, Jin H, Zheng R, Kim S, Lee SE, Kim BH, Yim SV. Cognition enhancing effect of Panax ginseng in Korean volunteers with mild cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial. Transl Clin Pharmacol 2019;27:92-7. https://doi.org/10.12793/tcp.2019.27.3.92
  26. Lee ST, Chu K, Sim JY, Heo JH, Kim M. Panax ginseng enhances cognitive performance in Alzheimer disease. Alzheimer Dis Assoc Disord 2008;22:222-6. https://doi.org/10.1097/WAD.0b013e31816c92e6
  27. Heo JH, Lee ST, Chu K, Oh MJ, Park HJ, Shim JY, Kim M. An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer's disease. Eur J Neurol 2008;15:865-8. https://doi.org/10.1111/j.1468-1331.2008.02157.x
  28. Heo JH, Lee ST, Oh MJ, Park HJ, Shim JY, Chu K, Kim M. Improvement of cognitive deficit in Alzheimer's disease patients by long term treatment with Korean red ginseng. J Ginseng Res 2011;35:457-61. https://doi.org/10.5142/jgr.2011.35.4.457
  29. Heo JH, Lee ST, Chu K, Oh MJ, Park HJ, Shim JY, Kim M. Heat-processed ginseng enhances the cognitive function in patients with moderately severe Alzheimer's disease. Nutr Neurosci 2012;15:278-82. https://doi.org/10.1179/1476830512Y.0000000027
  30. Heo JH, Park MH, Lee JH. Effect of Korean red ginseng on cognitive function and quantitative eeg in patients with Alzheimer's disease: a preliminary study. J Alternative Compl Med 2016;22:280-5. https://doi.org/10.1089/acm.2015.0265
  31. Bell L, Whyte A, Duysburgh C, Marzorati M, Van den Abbeele P, Le Cozannet R, Fanca-Berthon P, Fromentin E, Williams C. A randomized, placebo-controlled trial investigating the acute and chronic benefits of American Ginseng (Cereboost®) on mood and cognition in healthy young adults, including in vitro investigation of gut microbiota changes as a possible mechanism of action. Eur J Nutr 2022;61:413-28. https://doi.org/10.1007/s00394-021-02654-5
  32. Yeo HB, Yoon HK, Lee HJ, Kang SG, Jung KY, Kim L. Effects of Korean red ginseng on cognitive and motor function: a double-blind, randomized, placebo-controlled trial. J Ginseng Res 2012;36:190-7. https://doi.org/10.5142/jgr.2012.36.2.190
  33. Namgung E, Kim J, Jeong H, Hong G, Kim M, Kim RY, Kim S, Lyoo IK. Effects of Korean red ginseng on human gray matter volume and cognitive function: a voxel-based morphometry study. Hum Psychopharmacol 2021;36:e2767. https://doi.org/10.1002/hup.2767
  34. Moon J, Choi SH, Shim JY, Park HJ, Oh MJ, Kim M, Nah SY. Gintonin administration is safe and potentially beneficial in cognitively impaired elderly. Alzheimer Dis Assoc Disord 2018;32:85-7. https://doi.org/10.1097/WAD.0000000000000213
  35. Nah SY. Ginseng ginsenoside pharmacology in the nervous system: involvement in the regulation of ion channels and receptors. Front Physiol 2014;19:98.
  36. Choi SH, Jung SW, Lee BH, Kim HJ, Hwang SH, Kim HK, Nah SY. Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions. Front Pharmacol 2015;6:245.
  37. Wang Z, Zhang Z, Liu J, Guo M, Li H. Panax Ginseng in the treatment of Alzheimer's disease and vascular dementia. J Ginseng Res 2023;47:506-14. https://doi.org/10.1016/j.jgr.2023.03.001
  38. Tao R, Lu K, Zong G, Xia Y, Han H, Zhao Y, Wei Z, Lu Y. Ginseng polysaccharides: potential antitumor agents. J Ginseng Res 2023;47:9-22. https://doi.org/10.1016/j.jgr.2022.07.002
  39. Choi SH, Lee RM, Cho HS, Hwang SH, Hwang HI, Rhim H, Kim HC, Kim DG, Cho IH, Nah SY. Visualization of the binding between gintonin, a Panax ginseng-derived LPA receptor ligand, and the LPA receptor subtypes and transactivation of the EGF receptor. J Ginseng Res 2022;46:348-56. https://doi.org/10.1016/j.jgr.2021.10.004
  40. Lee R, Lee BH, Choi SH, Cho YJ, Cho HS, Kim HC, Rhim H, Cho IH, Rhee MH, Nah SY. Effects of Gintonin-enriched fraction on the gene expression of six lysophosphatidic receptor subtypes. J Ginseng Res 2021;45:583-90. https://doi.org/10.1016/j.jgr.2021.02.006
  41. White DJ, Camfield DA, Ossoukhova A, Savage K, Le Cozannet R, Fanca-Berthon P, Scholey A. Effects of Panax quinquefolius (American ginseng) on the steady state visually evoked potential during cognitive performance. Hum Psychopharmacol 2020;35:1-6.
  42. Scholey A, Ossoukhova A, Owen L, Ibarra A, Pipingas A, He K, Roller M, Stough C. Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an acute, randomized, double-blind, placebo-controlled, crossover study. Psychopharmacology (Berl) 2010;212:345-56. https://doi.org/10.1007/s00213-010-1964-y
  43. Sims JR, Zimmer JA, Evans CD, Evans CD, Lu M, Ardayfio P, Sparks J, Wessels AM, Shcherbinin S, Wang H, Nery ES, Sokovronsky MD. Donanemab in early symptomatic alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 2023;330:512-27. https://doi.org/10.1001/jama.2023.13239
  44. Reiss AB, Muhieddine D, Jacob B, Mesbah M, Pinkhasov A, Gomolin IH, Stecker MM, Wisniewski T, De Leon J. Alzheimer's disease treatment: the search for a breakthrough. Medicina (kaunas) 2023;59:1084.
  45. Kim HJ, Shin EJ, Lee BH, Choi SH, Jung SW, Cho IH, Hwang SH, Kim JY, Han JS, Chung C, Jang CG, Rhim H, Kim HC, Nah SY. Oral administration of gintonin attenuates cholinergic impairments by scopolamine, amyloid-β protein, and mouse model of Alzheimer's disease. Mol Cell 2015;38:796-805. https://doi.org/10.14348/molcells.2015.0116
  46. Kim S, Kim MS, Park K, Kim HJ, Jung SW, Nah SY, Han JS, Chung C. Hippocampus-dependent cognitive enhancement induced by systemic gintonin administration. J Ginseng Res 2016;40:55-61. https://doi.org/10.1016/j.jgr.2015.05.001
  47. Cho YJ, Choi SH, Lee RM, Cho HS, Rhim H, Kim HC, Kim BJ, Kim JH, Nah SY. Protective effects of gintonin on reactive oxygen species-induced ht22 cell damages: involvement of LPA1 receptor-BDNF-Akt signaling pathway. Molecules 2021;26:4138.
  48. Lim HK, Kim K, Son YK, Nah SY, Ahn SM, Song M. Gintonin stimulates dendritic growth in striatal neurons by activating Akt and CREB. Front Mol Neurosci 2022;15:1014497.
  49. Hwang SH, Shin EJ, Shin TJ, Lee BH, Choi SH, Kang J, Kim HJ, Kwon SH, Jang CG, Lee JH, Kim HC, Nah SY. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing. J Alzheimers Dis 2012;31:207-23. https://doi.org/10.3233/JAD-2012-120439
  50. Shin SJ, Nam Y, Park YH, Kim MJ, Lee E, Jeon SG, Bae BS, Seo J, Shim SL, Kim JS, Han CK, Kim S, Lee YY, Moon M. Therapeutic effects of non-saponin fraction with rich polysaccharide from Korean red ginseng on aging and Alzheimer's disease. Free Radic Biol Med 2021;164:233-48. https://doi.org/10.1016/j.freeradbiomed.2020.12.454
  51. Wang N, Wang X, He M, Zheng W, Qi D, Zhang Y, Han CC. Ginseng polysaccharides: a potential neuroprotective agent. J Ginseng Res 2021;45:211-7. https://doi.org/10.1016/j.jgr.2020.09.002
  52. Shi Z, Chen H, Zhou X, Yang W, Lin Y. Pharmacological effects of natural medicine ginsenosides against Alzheimer's disease. Front Pharmacol 2022;13:952332.
  53. Yanagida K, Shimizu T. Lysophosphatidic acid, a simple phospholipid with myriad functions. Pharmacol Ther 2023;246:108421.
  54. Yung YC, Stoddard NC, Chun J. LPA receptor signaling: pharmacology, physiology, and pathophysiology. J Lipid Res 2014;55:1192-214. https://doi.org/10.1194/jlr.R046458
  55. Choi SH, Jung SW, Lee BH, Kim HJ, Hwang SH, Kim HK, Nah SY. Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions. Front Pharmacol 2015;6:245.
  56. Shin TJ, Kim HJ, Kwon BJ, Choi SH, Kim HB, Hwang SH, Lee BH, Lee SM, Zukin RS, Park JH, et al. Gintonin, a ginseng-derived novel ingredient, evokes longterm potentiation through N-methyl-D-aspartic acid receptor activation: involvement of LPA receptors. Mol Cell 2012;34:563-72. https://doi.org/10.1007/s10059-012-0254-4
  57. Park H, Kim S, Rhee J, Kim HJ, Han JS, Nah SY, Chung C. Synaptic enhancement induced by gintonin via lysophosphatidic acid receptor activation in central synapses. J Neurophysiol 2015;113:1493-500. https://doi.org/10.1152/jn.00667.2014
  58. Cho HJ, Choi SH, Kim HJ, Lee BH, Rhim H, Kim HC, Hwang SH, Nah SY. Bioactive lipids in gintonin-enriched fraction from ginseng. J Ginseng Res 2019;43:209-17. https://doi.org/10.1016/j.jgr.2017.11.006
  59. Lee R, Kim JH, Hwang H, Rhim H, Hwang SH, Cho IH, Kim DG, Kim HC, Nah SY. Preparation of red ginseng marc-derived gintonin and its application as a skin nutrient. Nutrients 2023;15:2574.
  60. Li R, Xu C, Zhong P, Wang K, Luo Y, Xiao L, Dai X, Han J, Zhang X. Efficacy of acupuncture and pharmacological therapies for vascular cognitive impairment with no dementia: a network meta-analysis. Front Aging Neurosci 2023;15:1181160.
  61. Ikram M, Jo MG, Park TJ, Kim MW, Khan I, Jo MH, Kim MO. Oral administration of gintonin protects the brains of mice against aβ-induced Alzheimer disease pathology: antioxidant and anti-inflammatory effects. Oxid Med Cell Longev 2021; 2021:6635552.
  62. Kim DG, Jang M, Choi SH, Kim HJ, Jhun H, Kim HC, Rhim H, Cho IH, Nah SY. Gintonin, a ginseng-derived exogenous lysophosphatidic acid receptor ligand, enhances blood-brain barrier permeability and brain delivery. Int J Biol Macromol 2018;14:1325-37.
  63. Choi SH, Lee NE, Cho HJ, Lee RM, Rhim H, Kim HC, Han M, Lee EH, Park J, Nah SY. Gintonin facilitates brain delivery of donepezil, a therapeutic drug for Alzheimer disease, through lysophosphatidic acid 1/3 and vascular endothelial growth factor receptors. J Ginseng Res 2021;45:264-72. https://doi.org/10.1016/j.jgr.2019.12.002
  64. Seo S, Nah SY, Lee K, Choi N, Kim HN. Triculture model of in vitro BBB and its application to study BBB-associated chemosensitivity and drug delivery in glioblastoma. Adv Funct Mater 2021;32:2106860.
  65. Jang M, Choi SH, Choi JH, Oh J, Lee RM, Lee NE, Cho YJ, Rhim H, Kim HC, Cho IH, et al. Ginseng gintonin attenuates the disruptions of brain microvascular permeability and microvascular endothelium junctional proteins in an APPswe/PSEN-1 double-transgenic mouse model of Alzheimer's disease. Exp Ther Med 2021;21:310.
  66. Lee WJ, Shin YW, Chang H, Shin HR, Kim WW, Jung SW, Choi SH, Kim M, Nah SY. Cognitive improvement effect of gintonin might be associated with blood-brain barrier permeability enhancement: dynamic contrast-enhanced MRI pilot study. Transl Clin Pharmacol 2021;29:21-32. https://doi.org/10.12793/tcp.2021.29.e2