Article Detail

Home > Article Detail
  • P-ISSN 1010-0695
  • E-ISSN 2288-3339

Review of Red Ginseng in terms of Mechanisms for Pharmacodynamics and Toxicity

Journal of Korean Medicine / Journal of Korean Medicine, (P)1010-0695; (E)2288-3339
2012, v.33 no.3, pp.200-230




  • Downloaded
  • Viewed

Abstract

Objectives: Ginseng, Panax ginseng C. A., white ginseng, has been used for thousands of years in Traditional Korean Medicine. Red ginseng can be made by a steaming process of white ginseng changing a variety of ginsenosides and ingredients such as dencichine. This article reviews red ginseng for mechanisms for pharmacodynamics and toxicity based on the content of ginseng’s active ingredients, ginsenoside changed by steaming. Methods: The following electronic databases were searched: PubMed, Science Direct and Chinese Scientific Journals full text database (CQVIP), and KSI (Korean Studies Information) from their respective inceptions to June 2012. Results: Compared with unsteamed ginseng, the content of ginsenosides Rg2, Rg3, Rg5, Rh1, Rh2 and Rk1 called red ginseng-specific ginsenosides increased after the steaming process. Different ginsenosides have shown a wide variety of effects such as lowering or raising blood sugar and blood pressure or stimulating or sedating the nervous system. Especially, the levels of Rg2, Rg3, Rg5, Rh1, Rh2 and Rk1 were increased by the steaming process, showing a variety of pharmacodynamics in biological systems. Also, various processing methods such as puffing and fermentation have been developed in processing crude ginseng or red ginseng, affecting the content of ginseng’s ingredients. The safety issue could be the most critical, specifically, on changed ginseng’s ingredients such as dencichine. The level of dencichine was significantly reduced in red ginseng by the steaming process. In addition, the possible toxicity for red ginseng was affected by cytochrome P450, a herbal-drug interaction. Conclusions: The variety of pharmacological and toxicological properties should be changed by steaming process of Panax ginseng C. A., white ginseng. Even if it is not sure whether the steaming process of white ginseng would be better pharmacologically, it is sure that steaming reduces the level of dencichine causing a lower toxicity to the nervous system.

keywords
red ginseng, ginsenosides, pharmacodynamics, toxicity, dencichine


Reference

1

1. Korean ginseng. 2012. Available at:URL: http://www.ko.wikipedia.org/wiki/red ginseng. Accessed June 3, 2012.

2

2. Cheng LQ, Na JR, Bang MH, Kim MK, Yang DC. Conversion of major ginsenoside Rb1 to 20(S)-ginsenoside Rg3 by Microbacterium sp. GS514. Phytochemistry. 2008;69:218-224.

3

3. Hong HD, Kim YC, Rho J, Kim KT. Changes on Physicochemical Properties of Panax ginseng C. A. Meyer during Repeated Steaming Process. J. Ginseng Res. 2007;31(4):222-229.

4

4. Nam KY. The comparative understanding between Red ginseng and White ginsengs, Processed ginsengs(Panax ginseng C.A. Meyer). J. Jinseng Res. 2005;29(1):1-18.

5

5. Shi S, Wang CZ, Tong R, Li X, Fishbein A. Effects of steaming the root of Panax notoginseng on chemical composition and anticancer activities, Food Chemistry. 2010; 118:307-307.

6

6. Liu M, Zhang JT. Protective effects of ginsenoside Rb1 and Rg1 on cultured hippocampal neurons. Yao Xue Xue Bao. 1995;674-678.

7

7. Kim YC, Kim SR, Markelonis GJ, Oh TH. Ginsenosides Rb1 and Rg3 protect cultured rat cortical cells from glutamate-induced neurodegeneration. Journal of Neuroscience Research. 1998;53:426-432.

8

8. Chen HS, Pellegrini JW, Aggarwal SK, Lei SZ, Warach S, Jensen FE, et al. Open-channel block of N-methyl-d-aspartate(NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. Journal of Neuroscience. 1992;12:4427-4436.

9

9. Gervais FG, Xu D, Robertson GS, Vaillancourt JP, Zhu Y, Huang J, et al.. Involvement of caspases in proteolytic cleavage of Alzheimer’'s amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell. 1999;97:395-406.

10

10. Na L, Bin L, Dean E. Dluzen YJ. Protective effects of ginsenoside Rg2 against glutamate-induced neurotoxicity in PC12 cells. Journal of Ethnopharmacology. 2007;111: 458-463.

11

11. Blomgren K, Zhu C, Wang X, Karlsson JO, Leverin, AL, Bahr BA, et al.. Synergistic activation of caspase-3 by m-calpain after neonatal hypoxia- ischemia: a mechanism of “"pathological apoptosis”"? Journal of Biological Chemistry. 2001;276:10191-10198.

12

12. Zhang G, Liu A, Zhou Y, San X, Jin T, Jin Y. Panax ginseng ginsenoside-Rg2 protects memory impairment via anti-apoptosis in a rat model with vascular dementia. Journal of Ethnopharmacology. 2008; 115:441-448.

13

13. Miyashita T, Reed JC. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 1995;80:293-299.

14

14. Morrison RS, Wenzel HJ, Kinoshita Y, Robbins CA, Donehower LA, Schwartzkroin PA. Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death. Journal of Neuroscience. 1996;16:1337-1345.

15

15. Shinkai K, Akedo H, Mukai M, Imamura F, Isoai A, Kobayashi M, et al. Inhibitory of in vitro tumor cell invasion by ginsenoside Rg3. Jpn J Cancer Res. 1996;87:357-362.

16

16. Liu WK, Xu SX, Che CT. Anti-proliferative effect of ginseng saponins on human prostate cancer cell line. Life Sci. 2000;67:1297-1306.

17

17. Mochizuki M, Yoo YC, Matsuzawa K, Sato K, Saiki I, Tono-oka S, et al. Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside- Rb2, 20 (R) – and 20 (R) –ginsenoside- Rg3, of Red ginseng. Biol Pharm Bull. 1995; 18:1197-202.

18

18. Tao H, Yao M, Zou S, Zhao D, Qiu H. Effect of angiogenesis inhibitor Rg3 on the growth and metastasis of gastric cancer in SCID mice. Zhounghua Wai Ke Za Zhi. 2002;40:606-608.

19

19. Yun TK, Lee YS, Lee YH, Kim SI, Yun HY. Anticarcinogenic effect of Panax ginseng C A. Meyer and identification of active compounds. J Korean Med Sci. 2001;16:S6-18.

20

20. Yue YK, Daisy YL, Wong PK. Wu PY, Leung NK, Mak HW, et al. The angiosuppressive effects of 20(R)- ginsenoside Rg3 Biochemical pharmacology, 2006;72:437-445.

21

21. Bocchino M, Marruchella A, Saltini C. Immunogenetics of severe respiratory infections: models for the development of new therapeutic strategies. Respiration. 2005;72:449-457.

22

22. Johnson LN, Koval M. Cross-talk between pulmonary injury, oxidant stress, and gap junctional communication. Antioxid Redox Signal. 2009; 11:355-367.

23

23. Herold S, Tabar TS, Janssen H, Hoegner K, Cabanski M, Lewe-Schlosser P, et al. Exudate macrophages attenuate lung injury by the release of IL-1 receptor antagonist in Gram-negative pneumonia. Am J Respir Crit Care Med. 2011; 183:1380-1390.

24

24. Fairweather D, Rose NR. Inflammatory heart disease: a role for cytokines. Lupus. 2005;14: 646-651.

25

25. Lele RD. Beyond reverse pharmacology: mechanism- based scereening of ayurvedic drugs, Journal of Ayurveda & Integrative Medicine. 2010;1(4):257-265.

26

26. Kim TW, Joh EH, Kim B, Kim DH. Ginsenoside Rg5 ameliorates lung inflammation in mice by inhibiting the binding of LPS to toll-like receptor- 4 on macrophages, international Immunopharmacology. 2012;12:110-116.

27

27. Niu J, Kolattukudy PE. Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications. Clin Science. 2009;117:95- 109.

28

28. Ashida N, Arai H, Yamasaki M, Kita T. Distinct signaling pathways for MCP-1-dependent integrin activation and chemotaxis. J Biol Chem. 2001;276:16555-16560.

29

29. Choi YJ, Yoon JH, Cha SW, Lee SG. Ginsenoside Rh1 inhibits the invasion and migration of THP-1 acute monocytic leukemia cells via inactivation of the MAPK signaling pathway. Fitoterapia. 2011;82:911-919.

30

30. Weisz A. Estrogen stimulates transcription of c-jun protooncogene. Mol Endocrinol. 1990;4: 1041-1050.

31

31. Lin CY. Discovery of estrogen receptor alpha target genes and response elements in breast tumor cells. Genome Biol. 2004;5(9):R66.

32

32. White TE, Gasiewicz TA. The human estrogen receptor structural gene contains a DNA sequence that binds activated mouse and human Ah receptors: a possible mechanism of estrogen receptor regulation by 2,3,7,8-tetrachlorodibenzopdioxin, Biochem Biophys Res Commun. 1993; 193:956-962.

33

33. Lee YJ, Jin YR, Lim WC, Ji SM, Choi S, Jang S, et al. A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen receptor in human breast carcinoma MCF-7 cells. Journal of Steroid Biochemistry & Molecular Biology. 2003;84:463-468.

34

34. Kim SY, Jung SH, Kim HS. Curcumin is a potent broad spectrum inhibitor of matrix metalloproteinase gene expression in human astroglioma cells. Biochem Biophys Res Commun. 2005;337:510-516.

35

35. Laurent M, Martinerie C, Thibout H, Hoffman MP, Verrecchia F, Le Bouc Y, et al. NOVH increases MMP3 expression and cell migration in glioblastoma cells via a PDGFR-alpha-dependent mechanism. FASEB J. 2003;17:1919-1921.

36

36. Sounni NE, Devy L, Hajitou A, Frankenne F, Munaut C, Gilles C, et al. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression. FASEB J. 2002;16: 555-564.

37

37. Kim SY, Kim DH, Han SJ, Hyun JW, Kim JS. Repression of matrix metalloproteinase gene expression by ginsenoside Rh2 in human astroglioma cells. Expression biochemical pharmacology. 2007; 74:1642-1651.

38

38. Oh JI, Chun KH, Joo SH, Oh YT, Lee SK. Caspase-3-dependent protein kinase C delta activity is required for the progression of Ginsenoside-Rh2-induced apoptosis in SK-HEP- 1 cells. Cancer Letters. 2005;230:228-238.

39

39. Gregoire FM, Smas CM , Sul HS. Understanding adipocyte differentiation. Physiol. Rev. 1998;78: 783-809.

40

40. Ericsson J, Jackson SM, Kim JB, Spiegelman BM. Edwards PA. Identification of glycerol- 3-phosphate acyltransferase as an adipocyte determination and differentiation factor 1- and sterol regulatory elementbinding protein-responsive gene. J. Biol. Chem. 1997;272:7298- 7305.

41

41. Ron FM, Stephen RF. Hormonal Signaling and Transcriptional Control of Adipocyte Differentiation. The journal of nutrition. 2000: supplement:3111S-3121S.

42

42. Zang M, Xu S, Maitland-Toolan KA, Zuccollo A, Hou X, Jiang A, et al. Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice, Diabetes. 2006;55: 2180-2191.

43

43. Lin CL, Huang HC, Lin JK. Theaflavins attenuate hepatic lipid accumulation through activating AMPK in human HepG2 cells. J. Lipid Res. 2007;Epub ahead of print.

44

44. Fryer LG, Parbu-Patel A, Carling D. The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways, J. Biol. Chem. 2002; 277:25226-25232.

45

45. Hwang JT, Kim SH, Lee MS, Kim SH, Yang HJ, Kim MJ, et al.. Anti-obesity effects of ginsenoside Rh2 are associated with the activation of AMPK signaling pathway in 3T3-L1 adipocyte Biochemical and Biophysical Research Communications. 2007;364:1002-1008.

46

46. Park YC, Ko YD, Kim MK. Effects of estrogen, aging and oxidative stress on bone remodelling in a view of molecular mechanisms. J.Toxicol. Pub. Health. 2006;22(3):253-266.

47

47. Lee S, Maharjan S, Kim K, Kim MJ, Choi HJ, Kwon YJ, et al. Cholesterol-derived novel anti- apoptotic agents on the structural basis of ginsenoside Rk1, G.Q. Zhao, X.X. Wang, Chin. Trad. Herbal Drugs. 1986;17:34-43.

48

48. Kim YJ, Kwon HC, Ko H, Park JH, Kim HY, Yoo JH, et al.. Antitumor activity of the ginsenoside Rk1 in human hepatocellular carcinoma cells through inhibition of telomerase activity and induction of apoptosis. Biological & Pharmaceutical Bulletin. 2008;31:826-830.

49

49. Spencer PS, Roy DN, Ludolph A. Lathyrism: evidence for role of the neuroexcitatory aminoacid BOAA. Lancet. 1986(2):1066-1067.

50

50. Hugon J, Ludolph AS, Spencer PS, Roldan S, Gimenez Dumas JL. Studies of the etiology and pathogenesis of motor neuron diseases. III. Magnetic cortical stimulation in patients with lathyrism, Acta Neurol. Scand. 1993;88:412-416.

51

51. Park H, Cho BG, Lee MK. Nitrogen Compounds of Korea Ginseng and Their Physiological Significance, Korean J. Ginseng Sci. 1990;14(2): 317-331.

52

52. Van Damme P, Van Den Bosch L, Van Houtte E, Callewaert G, Robberecht W. GluR2-dependent properties of AMPA receptors determine the selective vulnerability of motor neurons to excitotoxicity, J. Neurophysiol. 2002; 88:1279-1287.

53

53. Yano K, Higashida H, Inoue R, Nozawa Y. Bradykinin-induced rapid breakdown of phosphatidylinositol 4,5-bisphosphate in neuroblastoma X glioma hybrid NG108-15 cells, J. Biol. Chem. 1984;259:10201-10207.

54

54. Foskett JK, White C, Cheung KH, Mak DO. Inositol trisphosphate receptor Ca2+ release channels, Physiol. Rev. 2007;87:593-658.

55

55. Van MM, Decrock E, Coussee E, Faes L, Vuyst ED, Vranckx K, et al. l-ODAP alters mitochondrial Ca2+ handling as an early event in excitotoxicity. Cell Calcium. 2010;47:287-96.

56

56. Park YC. The molecular & biochemical pronciples of toxiciology. Korean Studies Information LTD. 2010;ISBN:978-89-268-1259-4.

57

57. Park YC, Lee SD. The Toxicokinetic Characteristics of Korean Traditional Medicines. The Korean journal of Oriental preventive medicien. 2011;15(2):1-19.

58

58. Lee NH, Gue SC. Systematic Review of Randomized Controlled Trials Evaluating the Efficacy and Safety of Ginseng. J Acupunct Meridian Stud. 2011;4(2):85-97.

59

59. Siegel RK. Ginseng abuse syndrome.” Journal of the American Medical Association. 1979;241: 15-23.

60

60. Lee YJ, Chung E, Lee KY, Lee YH, Huh B, Lee SK. Ginsenoside-Rg1, one of the major active molecules from Panax ginseng is a functional ligand of glucocorticoid receptor. Molecular and Cellular Endocrinology. 1997; 133:135-140.

61

61. Lee JY, Lim KM, Kim SY, Bae ON, Noh JY, Chung SM, et al. Vascular Smooth Muscle Dysfunction and Remodeling Induced by Ginsenoside Rg3. a Bioactive Component of Ginseng, Toxicoligical science. 2010;117(2); 505-514.

62

62. Hashimoto K, Satoh K, Murata P, Makino B, Sakakibara I, Kase Y, et al. Components of Panax ginseng that improve accelerated small intestinal transit, J. Ethnopharmacol. 2003;84:115-119.

63

63. Rudakewich M, Ba F, Benishin CG. Neurotrophic and neuroprotective actions of ginsenosides Rb(1) and Rg(1), Planta Med. 2001;67: 533-537.

64

64. Seely D, Dugoua JJ, Perri D, Mills E. Koren G. Safety and efficacy of panax ginseng during pregnancy and lactation. Can J Clin Pharmacol. 2008;15:e87-e94.

65

65. Sticher O. Saponine in Pharmakognosie, Phytopharmazie. Hänsel R. & Sticher O. (eds.), Springer Verlag. Heidelberg. 2009;943-989.

66

66. MDidea. Exporting Division Extracts Profession al. Available at:URL:www.MDidea.com. Access ed June 20, 2012.

  • Downloaded
  • Viewed
  • 0KCI Citations
  • 0WOS Citations

Other articles from this issue

Recommanded Articles

상단으로 이동

Journal of Korean Medicine