한국약용작물학회지 (Korean Journal of Medicinal Crop Science)

  • 제28권1호
  • /
  • Pages.9-20
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  • 2020
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  • 1225-9306(pISSN)
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  • 2288-0186(eISSN)
한국약용작물학회 (The Korean Society of Medicinal Crop Science)
권호 표지
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인삼 품종별 뿌리 추출물의 NMDA 수용체 길항 효과 및 진세노사이드 함량

N-Methyl-D-Aspartate (NMDA) Receptor Antagonistic Effect and Ginsenoside Content of Panax ginseng C. A. Meyer Cultivar Root Extracts

  • 이승은 (국립원예특작과학원 인삼특작부 인삼특작이용팀) ;
  • 김장욱 (국립원예특작과학원 인삼특작부 인삼특작이용팀) ;
  • 정현수 (국립원예특작과학원 인삼특작부 인삼특작이용팀) ;
  • 최재훈 (국립원예특작과학원 인삼특작부 인삼특작이용팀) ;
  • 지윤정 (국립원예특작과학원 인삼특작부 인삼특작이용팀) ;
  • 김형돈 (국립원예특작과학원 인삼특작부 인삼특작이용팀) ;
  • 장귀영 (국립원예특작과학원 인삼특작부 인삼특작이용팀) ;
  • 현동윤 (국립원예특작과학원 인삼특작부 인삼특작이용팀) ;
  • 김동휘 (국립원예특작과학원 인삼특작부 인삼특작이용팀)
  • 투고 : 2019.10.18
  • 심사 : 2019.12.26
  • 발행 : 2020.02.28
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초록

Background: Although a number of Panax ginseng cultivars have been developed by Korean researchers in recent years, there has been insufficient analysis of their beneficial properties. In this study, we sought to identify useful ginseng varieties as functional materials. Methods and Results: We evaluated effects of root extracts of 10 ginseng cultivars (Cheongsun; CS, Chunpoong; CP, Gopoong; GP, Gumpoong; GMP, K1, Sunhyang; SH, Sunone; SO, Sunpoong; SP, Sunun; SU and Yunpoong; YP) against the inhibitory effects of nitric oxide (NO) and reactive oxygen species (ROS) production in mouse brain microglial BV2 cells, as well as the binding of N-methyl-D-aspartate receptor (NMDAR), a marker related to memory. Ginsenosides, such as 20 (S)-protopanaxadiols (PPDs), including ginsenoside-Rb1, -Rb2, -Rb3, -Rc, -Rd, and - Rg3 and 20 (S)-protopanaxatriols (PPTs) including -Re, -Rg1, and -Rg2 were analyzed by HPLC. We observed that the cultivar GMP showed the highest inhibitory effect (60.8%) against NO production at 20 ㎍/㎖. Those cultivars showing the significantly highest inhibition effects against ROS at 20 ㎍/㎖ were K1 (57.3%), SP (54.5%), YP (53.1%), CP (51.7%), CS (50.9%) and SH (49.6%). At 50 ㎍/㎖, K1 showed the most potent inhibitory effect (51.2%) on NMDAR binding. The total phenol content of SH (1.89 mg/g) and K1 (1.73 mg/g) were higher than those of the other cultivars, whereas in terms of PD/PT ratios, the values of CP (0.98), K1 (1.05) and SO (1.05) were lower than those of the other cultivars. On the basis of correlation coefficient (0.7064) between NMDAR inhibition and ONOO- scavenging activity. Conclusions: The findings of this study indicate that the cultivars K1 and SH could be useful ginseng resources as functional materials with favorable cognition-improving and antioxidative properties.

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참고문헌

  1. Ahn IO, Lee SS, Lee JH, Lee MJ and Jo BG. (2008). Comparison of ginsenoside contents and pattern similarity between root parts of new cultivars in Panax ginseng C. A. Meyer. Journal of Ginseng Research. 32:15-18.
  2. Ambriz-Perez DL, Leyva-Lopez N, Gutierrez-Grijalva EP and Heredia JB. (2016). Phenolic compounds: Natural alternative in inflammation treatment. a review. Cogent Food and Agriculture. 2: 1131412. http://dx.doi.org/10.1080/23311932.2015.1131412 (cited by 2019 Oct 13).
  3. Attele AS, Zhou YP, Xie JT, Wu JA, Zhang L, Dey L, Pugh W, Rue PA, Polonsky KS and Yuan CS. (2002). Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component. Diabetes. 51:1851-1858. https://doi.org/10.2337/diabetes.51.6.1851
  4. Boje KM and Arora PK. (1992). Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Research. 587:250-256. https://doi.org/10.1016/0006-8993(92)91004-X
  5. Carvajal FJ, Mattison HA and Cerpa W. (2016). Role of NMDA receptor-mediated glutamatergic signaling in chronic and acute neuropathologies. Neural Plasticity. 2701526. http://dx.doi.org/10.1155/2016/2701526 (cited by 2019 Nov 12).
  6. Chao CC, Hu S, Molitor TW, Shaskan EG and Peterson PK. (1992). Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. Journal of Immunology. 149:2736-2741.
  7. Cho IH. (2015). Volatile compounds of ginseng(Panax sp.): A review. Journal of the Korean Society for Applied Biological Chemistry. 58:67-75.
  8. Choi CS, Kim KI, Hong HD, Choi SY, Lee YC, Kim KT, Rho JH, Kim SS and Kim YC. (2006). Phenolic acid composition and antioxidative activity of white ginseng(Panax ginseng, C. A. Meyer). Journal of Ginseng Research. 30:22-30.
  9. Chung AS, Cho KJ, Oh JH and Park JD. (2004). Pharmacological and physiological effects of ginseng. Journal of Korean Association of Cancer Prevention. 9:125-138.
  10. Chung IM, Lim JJ, Ahn MS, Jeong HN, An TJ and Kim SH. (2016). Comparative phenolic compound profiles and antioxidative activity of the fruit, leaves, and roots of Korean ginseng(Panax ginseng Meyer) according to cultivation years. Journal of Ginseng Research. 40:68-75. https://doi.org/10.1016/j.jgr.2015.05.006
  11. Gehrmann J, Matsumoto Y and Kreutzberg GW. (1995). Microglia: Intrinsic immuneffector cell of the brain. Brain Research Reviews. 20:269-287. https://doi.org/10.1016/0165-0173(94)00015-H
  12. Ginhoux F, Lim S, Hoeffel G, Low D and Huber T. (2013). Origin and differentiation of microglia. Frontiers in Cellular Neuroscience. https://doi: 10.3389/fncel.2013.00045 (cited by 2019 Oct 11).
  13. Han JS, Tak HS, Lee GS, Kim JS, Woo RJ and Choi JE. (2013). Comparison of ginsenoside content and ratio of root tissue according to root age and diameter in Panax ginseng C. A. Meyer. Korean Journal of Medicinal Crop Science. 21:342-347. https://doi.org/10.7783/KJMCS.2013.21.5.342
  14. Hansen E, Krautwald M, Maczureck A, Stuchbury G, Fromm P, Steele M, Schulz O, Benavente-Garcia O, Castillo J, Korner H and Munch G. (2010). A versatile high throughput screening system for the simultaneous identification of antiinflammatory and neuroprotective compounds. Journal of Alzheimer's Disease. 19:451-464.
  15. Hofseth LJ and Wargovich MJ. (2007). Inflammation, cancer and targets of ginseng1-3. Journal of Nutrition. 137:183-185.
  16. Jang DH, Lee HJ, Lee KJ, Kim KR, Won R, Lee SE and Shim I. (2019). White ginseng ameliorates depressive behavior and increases hippocampal 5-HT level in the stressed ovariectomized rats. BioMed Research International. 5705232. https://doi.org/10.1155/2019/5705232 (cited by 2019 Oct 1).
  17. Jeong HS, Jeong JT, Lee JH, Park CG, Choi JH, Jang GY, Kim JW, Chang JK, Kim DH and Lee SE. (2018). Comparison of anti-oxidative and anti-inflammatory effect of atractylodes interspecific hybrid cultivar roots. Korean Journal of Medicinal Crop Science. 26:391-400. https://doi.org/10.7783/KJMCS.2018.26.5.391
  18. Jin SH, Park JK, Nam KY, Park SN and Jung NP. (1999). Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice. Journal of Ethnopharmacology. 66:123-129. https://doi.org/10.1016/S0378-8741(98)00190-1
  19. Jung BS and Shin MG. (1990). Hyangyak-seangyak great encyclopedia. Young-Lim Publishing Co. Seoul, Korea. p.439-443.
  20. Jung HW, Yoon CH, Park KM, Han HS and Park YK. (2009). Hexane fraction of Zingiberis Rhizoma Crudus extract inhibits the production of nitric oxide and proinflammatory cytokines in LPS-stimulated BV2 microglial cells via the NF-kappaB pathway. Food and Chemical Toxicology. 47:1190-1197. https://doi.org/10.1016/j.fct.2009.02.012
  21. Kang OJ and Kim JS. (2016). Comparison of ginsenoside contents in different parts of Korean ginseng(Panax ginseng C. A. Meyer). Preventive Nutrition and Food Science. 21:389-392. https://doi.org/10.3746/pnf.2016.21.4.389
  22. Kim DS, Park EJ, Song JY, Park CM, Son HY, Hwang KK and Jee YH. (2008a). Protective effects of an acidic polysaccharide of Panax ginseng on hematopoietic and immune systems of gamma-rays-irradiated mice. Laboratory Animal Research. 24:173-178.
  23. Kim GS, Hyun DY, Kim YO, Lee SW, Kim YC, Lee SE, Son YD, Lee MJ, Park CG, Park HK, Cha SW and Song KS. (2008b). Extraction and preprocessing methods for ginsenosides analysis of Panax ginseng C. A. Mayer. Korean Journal of Medicinal Crop Science. 16:446-454.
  24. Kim JH, Yi YS, Kim MY and Cho JY. (2017a). Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. Journal of Ginseng Research. 41:435-443. https://doi.org/10.1016/j.jgr.2016.08.004
  25. Kim JS. (2016). Investigation of phenolic, flavonoid, and vitamin contents in different parts of Korean ginseng(Panax ginseng C. A. Meyer). Preventive Nutrition and Food Science. 21:263-270. https://doi.org/10.3746/pnf.2016.21.3.263
  26. Kim JW, Cho SY, Kim SH, Cho DH, Kim SM, Park CW, Shimizu T, Cho JY, Seo DB and Shin SS. (2017b). Effects of Korean ginseng berry on skin antipigmentation and antiaging via FoxO3a activation. Journal of Ginseng Research. 41:277-283. https://doi.org/10.1016/j.jgr.2016.05.005
  27. Kim KH, Lee DH, Lee HL, Kim CE, Jung KW and Kang KS. (2018). Beneficial effects of Panax ginseng for the treatment and prevention of neurodegenerative diseases: Past findings and future directions. Journal of Ginseng Research. 42:239-247. https://doi.org/10.1016/j.jgr.2017.03.011
  28. Kim MW, Lee JS and Choi KJ. (1982). Comparative studies on the chemical components in ginseng. Part I. The ginsenosides and the free sugars content of various ginseng plants. Korean Journal of Ginseng Science. 6:138-142.
  29. Kim YC, Kim JU, Bae BS, Kang JY, Kim DH, Hyun DY and Lee JS. (2017c). Distribution of stem vestige according to ginseng cultivars and determination of root age by ginsenoside types of red ginseng. Korean Journal of Medicinal Crop Science. 25:217-223. https://doi.org/10.7783/KJMCS.2017.25.4.217
  30. Korea Health Industry Development Institute(KHIDI). (2018). U.S FDA recent draft guidance for drug development of early Alzheimer's disease. Korea Health Industry Development Institute. Cheongju, Korea. https://www.khidi.or.kr/board/view?linkId=48715916&menuId=MENU01819. (cited by 2019 Aug 11).
  31. Lau FC, Bielinski DF and Jeseph JA. (2007). Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. Journal of Neuroscience Research. 85:1010-1017. https://doi.org/10.1002/jnr.21205
  32. Lee KW, Ji HM, Kim DW, Choi SM, Kim S and Yang EJ. (2013a). Effects of Hominis placenta on LPS-induced cell toxicity in BV2 microglial cells. Journal of Ethnopharmacology. 147:286-292. https://doi.org/10.1016/j.jep.2013.02.033
  33. Lee LS, Cho CW, Hong HD, Lee YC, Choi UK and Kim YC. (2013b). Hypolipidemic and antioxidant properties of phenolic compound-rich extracts from white ginseng(Panax ginseng) in cholesterol-fed rabbits. Molecules. 18:12548-12560. https://doi.org/10.3390/molecules181012548
  34. Lee S, Kim MG, Ko SK, Kim HK, Leem KH and Kim YJ. (2014). Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80. Journal of Ginseng Research. 38:89-96. https://doi.org/10.1016/j.jgr.2013.10.001
  35. Lee SE, Lee JH, Park CG, Kim HD, Lee YJ, Seo KH, Jeong HS, Chang JK and Kim DH. (2019). Evaluation of the in vitro activity of Glycyrrhiza cultivar roots. Korean Journal of Medicinal Crop Science. 27:115-125. https://doi.org/10.7783/KJMCS.2019.27.2.115
  36. Leung KW and Wong AS. (2010). Pharmacology of ginsenosides: A literature review. Chinese Medicine. 5:20. http://www.cmjournal.org/content/5/1/20 (cited by 2019 Nov 13). https://doi.org/10.1186/1749-8546-5-20
  37. Li XG, Kang SJ, Han JS, Kim JS and Choi JE. (2009). Effects of root diameter within different root parts on ginsenoside composition of Yunpoong cultivar in Panax ginseng C. A. Meyer. Journal of Medicinal Crop Science. 17:452-457.
  38. Lopes JP, Tarozzo G, Reggiani A, Piomelli D and Cavalli A. (2013). Galantamine potentiates the neuroprotective effect of memantine against NMDA-induced excitotoxicity. Brain and Behavior. 3:67-74. https://doi.org/10.1002/brb3.118
  39. Magnusson KR, Brim BL and Das SR. (2010). Selective vulnerabilities of N-methyl-D-aspartate(NMDA) receptors during brain aging. Frontiers in Aging Neuroscience. Article 11. https://doi.org/10.3389/fnagi.2010.00011 (cited by 2019 Dec 12).
  40. Mota SI, Ferreira IL and Rego AC. (2014). Dysfunctional synapse in Alzheimer's disease-a focus on NMDA receptors. Neuropharmacology. 76:16-26. https://doi.org/10.1016/j.neuropharm.2013.08.013
  41. Nag SA, Qin JJ, Wang W, Wang MH, Wang H and Zhang R. (2012). Ginsenosides as anticancer agents: In vitro and in vivo activities, structure-activity relationships, and molecular mechanisms of action. Frontiers in Pharmacology. 3:25. https://www.frontiersin.org/articles/10.3389/fphar.2012.00025/full. (cited by 2019 July 11)
  42. Parsons CG, Stoffler A and Danysz W. (2007). Memantine: A NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system-too little activation is bad, too much is even worse. Neuropharmacology. 53:699-723. https://doi.org/10.1016/j.neuropharm.2007.07.013
  43. Rausch WD, Liu S, Gille G and Radad K. (2006). Neuroprotective effects of ginsenosides. Acta Neurobiologiae Experimentalis. 66:369-375.
  44. Razgonova MP, Veselov VV, Zakharenko AM, Golokhvast KS, Nosyrev AE, Cravotto G, Tsatsakis A and Spandidos DA. (2019). Panax ginseng components and the pathogenesis of Alzheimer's disease. Molecular Medicine Reports. 19:2975-2998.
  45. Reay JL, Kennedy DO and Scholey AB. (2005). Single doses of Panax ginseng(G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity. Journal of Psychopharmacology. 19:357-365. https://doi.org/10.1177/0269881105053286
  46. Siddiqi MH, Siddiqi MZ, Ahn S, Kang S, Kim YJ, Sathishmumar N, Yang DU and Yang DC. (2013). Ginseng saponins and the treatment of osteoporosis: Mini literature review. Journal of Ginseng Research. 37:261-268. https://doi.org/10.5142/jgr.2013.37.261
  47. Sills MA, Fagg G, Pozza M, Angst C, Brundish DE, Hurt SD, Wilusz EJ and Williams M. (1991). [$^3H$]CGP 39653: A new N-methyl-D-aspartate antagonist radioligand with low nanomolar affinity in rat brain. European Journal of Pharmacology. 192:19-24. https://doi.org/10.1016/0014-2999(91)90063-V
  48. Tungmunnithum D, Thongboonyou A, Pholboon A and Yangsabai A. (2018). Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: An overview. Medicines. 5:93. doi:10.3390/medicines5030093 (cited by 2019 Dec 14).
  49. Wang H, Peng D and Xie J. (2009). Ginseng leaf-stem: Bioactive constituents and pharmacological functions. Chinese Medicine. 4:20 doi:10.1186/1749-8546-4-20 (cited by 2019 Nov 5).
  50. Wang H, Wang J and Li G. (2016). A simple real-time polymerase chain reaction(PCR)-based assay for authentication of the Chinese Panax ginseng cultivar Damaya from a local ginseng population. Genetics and Molecular Research. 15:15028801. http://doi.org/10.4238/gmr.15028801 (cited by 2019 Oct 1).
  51. Wang Y, Li Y, Yang W, Gao S, Lin J, Wang T, Zhou K and Hu H. (2018). Ginsenoside Rb1 inhibit apoptosis in rat model of Alzheimer's disease induced by $A{\beta}1$-40. American Journal of Translational Research. 10:796-805.
  52. Yu T, Yang Y, Kwak YS, Song GG, Kim MY, Rhee MH and Cho JY. (2017). Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2. Journal of Ginseng Research. 41:127-133. https://doi.org/10.1016/j.jgr.2016.02.001
  53. Zheng M, Xin Y, Li Y, Xu F, Xi X, Guo H, Cui X, Cao H, Zhang X and Han C. (2018). Ginsenosides: A potential neuroprotective agent. BioMed Research International. 8174345. https://doi.org/10.1155/2018/8174345 (cited by 2019 Nov 13).
  54. Zhou X, Gan P, Hao L, Tao L, Jia J, Gao B, Liu JY, Zheng LT and Zhen X. (2014). Antiinflammatory effects of orientin-2"-O-galactopyranoside on lipopolysaccharide-stimulated microglia. Biological and Pharmaceutical Bulletin. 37:1282-1294. https://doi.org/10.1248/bpb.b14-00083