Skip to main content

Advertisement

Log in

Chemical components of ginseng, their biotransformation products and their potential as treatment of hypertension

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Ginseng is an ancient perennial herb belonging to the family Araliaceae and genus Panax which has been used for medical therapeutics for thousands of years, particularly in China and other Asian cultures although increasing interest in ginseng has recently emerged in western societies. Ginseng is a complex substance containing dozens of bioactive and potentially effective therapeutic compounds. Among the most studied are the ginsenosides, which are triterpene saponins possessing a wide array of potential therapeutic effects for many conditions. The quantity and type of ginsenoside vary greatly depending on ginseng species and their relative quantity in a given ginseng species is greatly affected by extraction processes as well as by subjecting ginseng to various procedures such as heating. Adding to the complexity of ginsenosides is their ability to undergo biotransformation to bioactive metabolites such as compound K by enteric bacteria following ingestion. Many ginsenosides exert vasodilatating effects making them potential candidates for the treatment of hypertension. Their vascular effects are likely dependent on eNOS activation resulting in the increased production of NO. One proposed end-mechanism involves the activation of calcium-activated potassium channels in vascular smooth cells resulting in reduced calcium influx and a vasodilatating effect, although other mechanisms have been proposed as discussed in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. He M, Huang X, Liu S, Guo C, Xie Y, Meijer AH, Wang M (2018) The difference between White and Red Ginseng: variations in ginsenosides and immunomodulation. Planta Med 84:845–854

    CAS  PubMed  Google Scholar 

  2. Attele AS, Wu JA, Yuan CS (1999) Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 58:1685–1693

    CAS  PubMed  Google Scholar 

  3. Garriques SS (1854) On panaquilon, a new vegetable substance. Ann Chem Pharm 90:231–234. https://doi.org/10.1002/jlac18540900216

    Article  Google Scholar 

  4. Shibata S, Tanaka O, NagaI M, Ishit T (1963) Studies on the constituents of Japanese and Chinese crude drugs XII Panaxadiol, a sapogenin of ginseng roots. Chem Pharm Bull (Tokyo) 11:762–765. https://doi.org/10.1248/cpb11762

    Article  CAS  Google Scholar 

  5. Shibata S, Ando T, Tanaka O, Meguro Y, Sôma K, Iida Y (1965) Saponins and sapogenins of Panax ginseng CA Meyer and some other Panax spp. Yakugaku Zasshi 85:753–755

    CAS  PubMed  Google Scholar 

  6. Shibata S, Tanaka O, Soma K, Aando T, Iida Y, Nakamura H (1965) Studies on saponins and sapogenins of ginseng. The structure of panaxatriol. Tetrahedron Lett 42:207–213

    CAS  PubMed  Google Scholar 

  7. Wang Y, Li X, Lin Y, Wang Y, Wang K, Sun C, Lu T, Zhang M (2018) Structural variation, functional differentiation, and activity correlation of the cytochrome P450 gene superfamily revealed in ginseng. Plant Genome 11:170106. https://doi.org/10.3835/plantgenome2017110106

    Article  CAS  Google Scholar 

  8. Zhao M, Lin Y, Wang Y, Li X, Han Y, Wang K, Sun C, Wang Y, Zhang M (2019) Transcriptome analysis identifies strong candidate genes for ginsenoside biosynthesis and reveals its underlying molecular mechanism in Panax ginseng CA Meyer. Sci Rep 9:615. https://doi.org/10.1038/s41598-018-36349-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shin BK, Kwon SW, Park JH (2015) Chemical diversity of ginseng saponins from Panax ginseng. J Ginseng Res 39:287–298. https://doi.org/10.1016/jjgr201412005

    Article  PubMed  PubMed Central  Google Scholar 

  10. Shibata S, Fujita M, Itokawa H, Tanko O, Ishii T (1963) Studies on the constituents of Japanese and Chinese Crude Drugs XI Panaxadiol, a sapogenin of ginseng roots (1). Chem Pharm Bull (Tokyo) 11:759–761

    CAS  Google Scholar 

  11. Jia L, Zhao Y (2009) Current evaluation of the millennium phytomedicine Ginseng (I): etymology, pharmacognosy, phytochemistry, market and regulations. Curr Med Chem 16:2475–2484

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Jia L, Zhao Y, Liang XJ (2009) Current evaluation of the millennium phytomedicine Ginseng (II): collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. Curr Med Chem 16:2924–2942

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Qi LW, Wang CZ, Yuan CS (2011) Isolation and analysis of ginseng: advances and challenges. Nat Prod Rep 28:467–495

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Xu QF, Fang XL, Chen DF (2005) Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats. J Ethnopharmacol 84:187–192

    Google Scholar 

  15. Yu K, Chen F, Li C (2012) Absorption, disposition, and pharmacokinetics of saponins from Chinese medicinal herbs: what do we know and what do we need to know more? Curr Drug Metab 13:577–598

    CAS  PubMed  Google Scholar 

  16. Yu H, Wang Y, Liu C, Yang J, Xu L, Li G, Song J, Jin F (2018) Conversion of ginsenoside Rb1 into six types of highly bioactive ginsenoside Rg3 and its derivatives by FeCl3 catalysis. Chem Pharm Bull (Tokyo) 66:901–906. https://doi.org/10.1248/cpbc18-00426

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  18. Fu Y, Yin ZH, Yin CY (2017) Biotransformation of ginsenoside Rb1 to ginsenoside Rg3 by endophytic bacterium Burkholderia sp GE 17-7 isolated from Panax ginseng. J Appl Microbiol 122:1579–1585. https://doi.org/10.1111/jam13435

    Article  CAS  PubMed  Google Scholar 

  19. Liu H, Pan J, Yang Y, Cui X, Qu Y (2018) Production of minor ginenosides from Panax notoginseng by microwave processing method and evaluation of their blood-enriching and hemostatic activity. Molecules 23:1243. https://doi.org/10.3390/molecules23061243

    Article  CAS  PubMed Central  Google Scholar 

  20. Yuan CS, Wang CZ, Wicks SM, Qi LW (2010) Chemical and pharmacological studies of saponins with a focus on American ginseng. J Ginseng Res 34:160–167. https://doi.org/10.5142/jgr2010343160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Li W, Fitzloff JF (2001) Determination of 24(R)-pseudoginsenoside F11 in North American ginseng using high performance liquid chromatography with evaporative light scattering detection. J Pharm Biomed Anal 25:257–265

    CAS  PubMed  Google Scholar 

  22. Schlag EM, McIntosh MS (2006) Ginsenoside content and variation among and within American ginseng (Panax quinquefolius L) populations. Phytochemistry 67:1510–1519

    CAS  PubMed  Google Scholar 

  23. Assinewe VA, Baum BR, Gagnon D, Arnason JT (2003) Phytochemistry of wild populations of Panax quinquefolius L (North American ginseng). J Agric Food Chem 51:4549–4553

    CAS  PubMed  Google Scholar 

  24. Kim WY, Kim JM, Han SB, Lee SK, Kim ND, Park MK, Kim CK, Park JH (2000) Steaming of ginseng at high temperature enhances biological activity. J Nat Prod 63:1702–1704

    CAS  PubMed  Google Scholar 

  25. Xu XF, Gao Y, Xu SY, Liu H, Xue X, Zhang Y, Zhang H, Liu MN, Xiong H, Lin RC, Li XR (2018) Remarkable impact of steam temperature on ginsenosides transformation from fresh ginseng to red ginseng. J Ginseng Res 42:277–287. https://doi.org/10.1016/jjgr201702003

    Article  PubMed  Google Scholar 

  26. Lee SM, Bae BS, Park HW, Ahn NG, Cho BG, Cho YL, Kwak YS (2015) Characterization of Korean Red Ginseng (Panax ginseng Meyer): history, preparation method, and chemical composition. J Ginseng Res 39:384–391. https://doi.org/10.1016/jjgr201504009

    Article  PubMed  PubMed Central  Google Scholar 

  27. Lee SM (2014) Thermal conversion pathways of ginsenoside in red ginseng processing. Nat Prod Sci 20:119–125

    CAS  Google Scholar 

  28. Sun BS, Gu LJ, Fang ZM, Wang CY, Wang Z, Sung CK (2009) Determination of 11 ginsenosides in black ginseng developed from Panax ginseng by high performance liquid chromatography. Food Sci Biotechnol 18:561–564

    CAS  Google Scholar 

  29. Metwaly AM, Lianlian Z, Luqi H, Deqiang D (2019) Black ginseng and its saponins: preparation, phytochemistry and pharmacological effects. Molecules 24:1856. https://doi.org/10.3390/molecules24101856

    Article  CAS  PubMed Central  Google Scholar 

  30. Wang CZ, Zhang B, Song WX, Wang A, Ni M, Luo X, Aung HH, Xie JT, Tong R, He TC, Yuan CS (2006) Steamed American ginseng berry: ginsenoside analyses and anticancer activities. J Agric Food Chem 54:9936–9942

    CAS  PubMed  Google Scholar 

  31. Lee MY, Singh D, Kim SH, Lee SJ, Lee CH (2016) Ultrahigh pressure processing produces alterations in the metabolite profiles of Panax ginseng. Molecules 21:816. https://doi.org/10.3390/molecules21060816

    Article  CAS  PubMed Central  Google Scholar 

  32. Kho MC, Lee YJ, Park JH, Kim HY, Yoon JJ, Ahn YM, Tan R, Park MC, Cha JD, Choi KM, Kang DG, Lee HS (2016) Fermented red ginseng potentiates improvement of metabolic dysfunction in metabolic syndrome rat models. Nutrients 8:369. https://doi.org/10.3390/nu8060369

    Article  CAS  PubMed Central  Google Scholar 

  33. Shin JH, Park YJ, Kim W, Kim DO, Kim BY, Lee H, Baik MY (2019) Change of ginsenoside profiles in processed ginsengs by drying, steaming, and puffing. J Microbiol Biotechnol 29:222–229. https://doi.org/10.4014/jmb180909056

    Article  PubMed  Google Scholar 

  34. Kim BG, Choi SY, Kim MR, Suhd HJ, Park HJ (2010) Changes of ginsenosides in Korean red ginseng (Panax ginseng) fermented by Lactobacillus plantarum M1. Process Biochem 45:1319–1324. https://doi.org/10.1016/jprocbio201004026

    Article  CAS  Google Scholar 

  35. Ligor T, Ludwiczuk A, Wolski T, Buszewski B (2005) Isolation and determination of ginsenosides in American ginseng leaves and root extracts by LC-MS. Anal Bioanal Chem 383:1098–1105

    CAS  PubMed  Google Scholar 

  36. Liu GY, Li XW, Wang NB, Zhou HY, Wei W, Gui MY, Yang B, Jin YR (2010) Three new dammarane-type triterpene saponins from the leaves of Panax ginseng CA Meyer. J Asian Nat Prod Res 12:865–873. https://doi.org/10.1080/102860202010508035

    Article  CAS  PubMed  Google Scholar 

  37. Attele AS, Zhou YP, Xie JT, Wu JA, Zhang L, Dey L, PughW RPA, Polonsky KS, Yuan CS (2002) Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component. Diabetes 51:1851–1858

    CAS  PubMed  Google Scholar 

  38. Dey L, Xie JT, Wang A, Wu J, Maleckar SA, Yuan CS (2003) Anti-hyperglycemic effects of ginseng: comparison between root and berry. Phytomedicine 10:600–605

    CAS  PubMed  Google Scholar 

  39. Kim HY, Kang KS, Yamabe N, Yokozawa T (2008) Comparison of the effects of Korean ginseng and heat-processed Korean ginseng on diabetic oxidative stress. Am J Chin Med 36:989–1004

    CAS  PubMed  Google Scholar 

  40. Kim GN, Lee JS, Song JH, Oh CH, Kwon YI, Jang HD (2010) Heat processing decreases Amadori products and increases total phenolic content and antioxidant activity of Korean red ginseng. J Med Food 13:1478–1484. https://doi.org/10.1089/jmf20101076

    Article  CAS  PubMed  Google Scholar 

  41. Lee HS, Lee HJ, Yu HJ, Ju do W, Kim Y, Kim CT, Kim CJ, Cho Y, Kim N, Choi SY, Suh HJ (2011) A comparison between high hydrostatic pressure extraction and heat extraction of ginsenosides from ginseng (Panax ginseng CA Meyer). J Sci Food Agric 9:1466–1473. https://doi.org/10.1002/jsfa4334

    Article  Google Scholar 

  42. Lee DC, Lee MO, Kim CY, Clifford DH (1981) Effect of ether, ethanol and aqueous extracts of ginseng on cardiovascular function in dogs. Can J Comp Med 45:182–187

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Gafner S, Bergeron C, McCollom MM, Cooper LM, McPhail KL, Gerwick WH, Angerhofer CK (2004) Evaluation of the efficiency of three different solvent systems to extract triterpene saponins from roots of Panax quinquefolius using high-performance liquid chromatography. J Agric Food Chem 52:1546–1550

    CAS  PubMed  Google Scholar 

  44. Ru W, Wang D, Xu Y, He X, Sun YE, Qian L, Zhou X, Qin Y (2015) Chemical constituents and bioactivities of Panax ginseng (CA Meyer). Drug Discov Ther 9:23–32

    CAS  PubMed  Google Scholar 

  45. Xiong X, Huang G, Huang H (2019) The antioxidant activities of phosphorylated polysaccharide from native ginseng. Int J Biol Macromol 126:842–845. https://doi.org/10.1016/jijbiomac201812266

    Article  CAS  PubMed  Google Scholar 

  46. Kobashi K, Akao T (1997) Relation of intestinal bacteria to pharmacological effects of glycosides. Biosci Microflora 16:1–7

    CAS  Google Scholar 

  47. Kim DH (2002) Herbal medicines are activated by intestinal microflora. Nat Prod Sci 8:35–43

    CAS  Google Scholar 

  48. Odani T, Tanizawa H, Takino Y (1983) Studies on the absorption, distribution, excretion and metabolism of ginseng saponins. II. The absorption, distribution and excretion of ginsenoside Rg1 in the rat. Chem Pharm Bull (Tokyo) 31:292–298

    CAS  Google Scholar 

  49. Odani T, Tanizawa H, Takino Y (1983) Studies on the absorption, distribution, excretion and metabolism of ginseng saponins. III. The absorption, distribution and excretion of ginsenoside Rb1 in the rat. Chem Pharm Bull (Tokyo) 31:1059–1066

    CAS  Google Scholar 

  50. Karikura M, Miyase T, Tanizawa H, Takino Y, Taniyama T, Hayashi T (1990) Studies on absorption, distribution, excretion and metabolism of ginseng saponins. V. The decomposition products of ginsenoside Rb2 in the large intestine of rats. Chem Pharm Bull (Tokyo) 38:2859–2861

    CAS  Google Scholar 

  51. Karikura M, Miyase T, Tanizawa H, Taniyama T, Takino Y (1991) Studies on absorption, distribution, excretion and metabolism of ginseng saponins. VII. Comparison of the decomposition modes of ginsenoside-Rb1 and -Rb2 in the digestive tract of rats. Chem Pharm Bull 39:2357–2361

    CAS  Google Scholar 

  52. Akao T, Kida H, Kanaoka M, Hattori M, Kobashi K (1998) Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng. J Pharm Pharmacol 50:1155–1160

    CAS  PubMed  Google Scholar 

  53. Bae EA, Choo MK, Park EK, Park SY, Shin HY, Kim DH (2002) Metabolism of ginsenoside R(c) by human intestinal bacteria and its related antiallergic activity. Biol Pharm Bull 25:743–747

    CAS  PubMed  Google Scholar 

  54. Bae EA, Han MJ, Kim EJ, Kim DH (2004) Transformation of ginseng saponins to ginsenoside Rh2 by acids and human intestinal bacteria and biological activities of their transformants. Arch Pharm Res 27:61–67

    CAS  PubMed  Google Scholar 

  55. Liu Y, Zhang JW, Li W, Ma H, Sun J, Deng MC, Yang L (2006) Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes. Toxicol Sci 91:356–364

    CAS  PubMed  Google Scholar 

  56. Tawab MA, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M (2003) Degradation of ginsenosides in humans after oral administration. Drug Metab Dispos 31:1065–1071

    PubMed  Google Scholar 

  57. Kim HK (2013) Pharmacokinetics of ginsenoside Rb1 and its metabolite compound K after oral administration of Korean Red Ginseng extract. J Ginseng Res 37:451–456. https://doi.org/10.5142/jgr201337451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hasebe T, Ueno N, Musch MW, Nadimpalli A, Kaneko A, Kaifuchi N, Watanabe J, Yamamoto M, Kono T, Inaba Y, Fujiya M, Kohgo Y, Daikenchuto CEB (2016) (TU-100) shapes gut microbiota architecture and increases the production of ginsenoside metabolite compound K. Pharmacol Res Perspect 10:e00215. https://doi.org/10.1002/prp2215

    Article  Google Scholar 

  59. Kim KA, Yoo HH, Gu W, Yu DH, Jin MJ, Choi HL, Yuan K, Guerin-Deremaux L, Kim DH (2015) A prebiotic fiber increases the formation and subsequent absorption of compound K following oral administration of ginseng in rats. J Ginseng Res 39:183–187. https://doi.org/10.1016/jjgr201411002

    Article  PubMed  Google Scholar 

  60. Akao T, Kanaoka M, Kobashi K (1998) Appearance of compound K, a major metabolite of ginsenoside Rb1 by intestinal bacteria, in rat plasma after oral administration—measurement of compound K by enzyme immunoassay. Biol Pharm Bull 21:245–249

    CAS  PubMed  Google Scholar 

  61. Chi H, Ji GE (2005) Transformation of ginsenosides Rb1 and Re from Panax ginseng by food microorganisms. Biotechnol Lett 27:765–771

    CAS  PubMed  Google Scholar 

  62. Chen GT, Yang M, Song Y, Lu ZQ, Zhang JQ, Huang HL, Wu LJ, Guo DA (2008) Microbial transformation of ginsenoside Rb(1) by Acremonium strictum. Appl Microbiol Biotechnol 77:1345–1350

    CAS  PubMed  Google Scholar 

  63. Zhou W, Yan Q, Li JY, Zhang XC, Zhou P (2008) Biotransformation of Panax notoginseng saponins into ginsenoside compound K production by Paecilomyces bainier sp 229. J Appl Microbiol 104:699–706. https://doi.org/10.1111/j1365-2672200703586x

    Article  CAS  PubMed  Google Scholar 

  64. Noh KH, Son JW, Kim HJ, Oh DK (2009) Ginsenoside compound K production from ginseng root extract by a thermostable beta-glycosidase from Sulfolobus solfataricus. Biosci Biotechnol Biochem 73:316–321

    CAS  PubMed  Google Scholar 

  65. Shen H, Leung WI, Ruan JQ, Li SL, Lei JP, Wang YT, Yan R (2013) Biotransformation of ginsenoside Rb1 via the gypenoside pathway by human gut bacteria. Chin Med 8:22. https://doi.org/10.1186/1749-8546-8-22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kim BH, Lee SY, Cho HJ, You SN, Kim YJ, Park YM, Lee JK, Baik MY, Park CS, Ahn SC (2006) Biotransformation of Korean Panax ginseng by Pectinex. Biol Pharm Bull 29:2472–2478

    CAS  PubMed  Google Scholar 

  67. Shin KC, Choi HY, Seo MJ, Oh DK (2015) Compound K production from Red Ginseng Extract by β-glycosidase from Sulfolobus solfataricus supplemented with α-L-Arabinofuranosidase from Caldicellulosiruptor saccharolyticus. PLoS One 10:e0145876. https://doi.org/10.1371/journalpone0145876

    Article  PubMed  PubMed Central  Google Scholar 

  68. Noh KH, Oh DK (2009) Production of the rare ginsenosides compound K, compound Y, and compound Mc by a thermostable beta-glycosidase from Sulfolobus acidocaldarius. Biol Pharm Bull 32:1830–1835

    CAS  PubMed  Google Scholar 

  69. Ma LY, Zhou QL, Yang XB, Wang HP, Yang XW (2016) Metabolism of 20(S)-ginsenoside Rg2 by rat liver microsomes: bioactivation to SIRT1-activating metabolites. Molecules 21:757. https://doi.org/10.3390/molecules21060757

    Article  CAS  PubMed Central  Google Scholar 

  70. Lackland DT, Weber MA (2015) Global burden of cardiovascular disease and stroke: hypertension at the core. Can J Cardiol 31:569–571. https://doi.org/10.1016/jcjca201501009

    Article  PubMed  Google Scholar 

  71. Poulter NR, Prabhakaran D, Caulfield M (2015) Hypertens Lancet 386:801–812. https://doi.org/10.1016/S0140-6736(14)61468-9

    Article  Google Scholar 

  72. NCD Risk Factor Collaboration (NCD-RisC) (2017) Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants. Lancet 389:37–55. https://doi.org/10.1016/S0140-6736(16)31919-5

    Article  Google Scholar 

  73. Carretero OA, Oparil S (2000) Essential hypertension: Part I: definition and etiology. Circulation 101:329–335

    CAS  PubMed  Google Scholar 

  74. Franco V, Oparil S, Carretero OA (2004) Hypertensive therapy: Part I. Circulation 109:2953–2958

    PubMed  Google Scholar 

  75. Franco V, Oparil S, Carretero OA (2004) Hypertensive therapy: Part II. Circulation 109:3081–3088

    PubMed  Google Scholar 

  76. Jalili J, Askeroglu U, Alleyne B, Guyuron B (2013) Herbal products that may contribute to hypertension. Plast Reconstr Surg 132:876e–877e. https://doi.org/10.1097/PRS0b013e3182a4c4a6

    Article  Google Scholar 

  77. Wood WB, Roh BL, White RP (1964) Cardiovascular actions of Panax ginseng in dogs. Jpn J Pharmacol 14:284–294

    CAS  PubMed  Google Scholar 

  78. Takagi K, Saito H, Nabata H (1972) Pharmacological studies of Panax ginseng root: estimation of pharmacological actions of Panax ginseng root. Jpn J Pharmacol 22:245–249

    CAS  PubMed  Google Scholar 

  79. Kaku T, Miyata T, Uruno T, Sako I, Kinoshita A (1975) Chemico-pharmacological studies on saponins of Panax ginseng C A Meyer. II. Pharmacological part. Arzneimittelforschung 25:539–547

    CAS  PubMed  Google Scholar 

  80. Chen X, Gillis CN, Moalli R (1984) Vascular effects of ginsenosides in vitro. Br J Pharmacol 82:485–491

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Lei XL, Chiou GC (1986) Cardiovascular pharmacology of Panax notoginseng (Burk) FH Chen and Salvia miltiorrhiza. Am J Chin Med 14:145–152

    CAS  PubMed  Google Scholar 

  82. Park JB, Kwon SK, Nagar H, Jung SB, Jeon BH, Kim CS, Oh JH, Song HJ, Kim CS (2014) Rg3-enriched Korean Red Ginseng improves vascular function in spontaneously hypertensive rats. J Ginseng Res 38:244–250. https://doi.org/10.1016/jjgr201405011

    Article  PubMed  PubMed Central  Google Scholar 

  83. Pan C, Huo Y, An X, Singh G, Chen M, Yang Z, Pu J, Li J (2012) Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation. Vasc Pharmacol 56:150–158. https://doi.org/10.1016/jvph201112006

    Article  CAS  Google Scholar 

  84. Loh YC, Tan CS, Ch’ng YS, Ng CH, Yeap ZQ, Yam MF (2019) Mechanisms of action of Panax notoginseng ethanolic extract for its vasodilatory effects and partial characterization of vasoactive compounds. Hypertens Res 42:182–194. https://doi.org/10.1038/s41440-018-0139-9

    Article  CAS  PubMed  Google Scholar 

  85. Hong SY, Kim JY, Ahn HY, Shin JH, Kwon O (2012) Panax ginseng extract rich in ginsenoside protopanaxatriol attenuates blood pressure elevation in spontaneously hypertensive rats by affecting the Akt-dependent phosphorylation of endothelial nitric oxide synthase. J Agric Food Chem 60:3086–3091. https://doi.org/10.1021/jf204447y

    Article  CAS  PubMed  Google Scholar 

  86. Baek EB, Yoo HY, Park SJ, Chung YS, Hong EK, Kim SJ (2009) Inhibition of arterial myogenic responses by a mixed aqueous extract of Salvia miltiorrhiza and Panax notoginseng (PASEL) showing antihypertensive effects. Korean J Physiol Pharmacol 13:287–293. https://doi.org/10.4196/kjpp2009134287

    Article  PubMed  PubMed Central  Google Scholar 

  87. Jeon BH, Kim CS, Park KS, Lee JW, Park JB, Kim KJ, Kim SH, Chang SJ, Nam KY (2000) Effect of Korea red ginseng on the blood pressure in conscious hypertensive rats. Gen Pharmacol 35:135–141

    CAS  PubMed  Google Scholar 

  88. Jeon BH, Kim CS, Kim HS, Park JB, Nam KY, Chang SJ (2000) Effect of Korean red ginseng on blood pressure and nitric oxide production. Acta Pharmacol Sin 21:1095–1100

    CAS  PubMed  Google Scholar 

  89. Wang L, Higashiura K, Ura N, Miura T, Shimamoto K (2003) Chinese medicine, Jiang-Tang-Ke-Li, improves insulin resistance by modulating muscle fiber composition and muscle tumor necrosis factor-alpha in fructose-fed rats. Hypertens Res 26:527–532

    CAS  PubMed  Google Scholar 

  90. Li X, Luo J, Anandh Babu PV, Zhang W, Gilbert E, Cline M, McMillan R, Hulver M, Alkhalidy H, Zhen W, Zhang H, Liu D (2014) Dietary supplementation of chinese ginseng prevents obesity and metabolic syndrome in high-fat diet-fed mice. J Med Food 17:1287–1297. https://doi.org/10.1089/jmf20140016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Yin J, Zhang H, Ye J (2008) Traditional chinese medicine in treatment of metabolic syndrome. Endocr Metab Immune Disord Drug Targets 8:99–111

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Yanai K, Sato K, Masuda S, Ikeda M, Kinae N (2006) Utilization study of stems and leaves of Tienchi Ginseng I Anti-hypertensive effect of stems and leaves of Tienchi Ginseng on stroke-prone spontaneously hypertensive rat (SHRSP). Biosci Biotechnol Biochem 70:2501–2507

    CAS  PubMed  Google Scholar 

  93. Cai BX, Li XY, Chen JH, Tang YB, Wang GL, Zhou JG, Qui QY, Guan YY (2009) Ginsenoside-Rd, a new voltage-independent Ca2+ entry blocker, reverses basilar hypertrophic remodeling in stroke-prone renovascular hypertensive rats. Eur J Pharmacol 606:142–149. https://doi.org/10.1016/jejphar200901033

    Article  CAS  PubMed  Google Scholar 

  94. Wu T, Sun J, Kagota S, Maruyama K, Wakuda H, Shinozuka K (2016) Panax notoginseng saponins ameliorate impaired arterial vasodilation in SHRSPZ-Lepr(fa)/lzmDmcr rats with metabolic syndrome. Clin Exp Pharmacol Physiol 43:459–467. https://doi.org/10.1111/1440-168112547

    Article  CAS  PubMed  Google Scholar 

  95. Kiesewetter H, Jung F, Mrowietz C, Wenzel E (1992) Hemorrheological and circulatory effects of Gincosan. Int J Clin Pharmacol Ther Toxicol 30:97–102

    CAS  PubMed  Google Scholar 

  96. Caron MF, Hotsko AL, Robertson S, Mandybur L, Kluger J, White CM (2002) Electrocardiographic and hemodynamic effects of Panax ginseng. Ann Pharmacother 36:758–763

    PubMed  Google Scholar 

  97. Han K, Shin IC, Choi KJ, Yun YP, Hong JT, Oh KW (2005) Korea red ginseng water extract increases nitric oxide concentrations in exhaled breath. Nitric Oxide 12:159–162

    CAS  PubMed  Google Scholar 

  98. Jovanovski E, Bateman EA, Bhardwaj J, Fairgrieve C, Mucalo I, Jenkins AL, Vuksan V (2014) Effect of Rg3-enriched Korean red ginseng (Panax ginseng) on arterial stiffness and blood pressure in healthy individuals: a randomized controlled trial. J Am Soc Hypertens 8:537–541. https://doi.org/10.1016/jjash201404004

    Article  CAS  PubMed  Google Scholar 

  99. Biaggioni I (2014) Ginseng for cardiovascular disease. Not yet the panacea. J Am Soc Hypertens 8:599–600. https://doi.org/10.1016/jjash201405012

    Article  PubMed  Google Scholar 

  100. Jovanovski E, Peeva V, Sievenpiper JL, Jenkins AL, Desouza L, Rahelic D, Sung MK, Vuksan V (2014) Modulation of endothelial function by Korean red ginseng (Panax ginseng CA Meyer) and its components in healthy individuals: a randomized controlled trial. Cardiovasc Ther 32:163–169. https://doi.org/10.1111/1755-592212077

    Article  CAS  PubMed  Google Scholar 

  101. Shishtar E, Jovanovski E, Jenkins A, Vuksan V (2014) Effects of Korean white ginseng (Panax ginseng CA Meyer) on vascular and glycemic health in Type 2 diabetes: results of a randomized, double blind, placebo-controlled, multiple-crossover, acute dose escalation trial. Clin Nutr Res 3:89–97. https://doi.org/10.7762/cnr20143289

    Article  PubMed  PubMed Central  Google Scholar 

  102. Vuksan V, Sung MK, Sievenpiper JL, Stavro PM, Jenkins AL, Di Buono M, Lee KS, Leiter LA, Nam KY, Arnason JT, Choi M, Naeem A (2008) Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr Metab Cardiovasc Dis 18:46–56

    PubMed  Google Scholar 

  103. Liang MT, Podolka TD, Chuang WJ (2005) Panax notoginseng supplementation enhances physical performance during endurance exercise. J Strength Cond Res 19:108–114

    PubMed  Google Scholar 

  104. Han KH, Choe SC, Kim HS, Sohn DW, Nam KY, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, Lee YW (1998) Effect of red ginseng on blood pressure in patients with essential hypertension and white coat hypertension. Am J Chin Med 26:199–209

    CAS  PubMed  Google Scholar 

  105. Sung J, Han KH, Zo JH, Park HJ, Kim CH, Oh BH (2000) Effects of red ginseng upon vascular endothelial function in patients with essential hypertension. Am J Chin Med 28:205–216

    CAS  PubMed  Google Scholar 

  106. Park BJ, Lee YJ, Lee HR, Jung DH, Na HY, Kim HB, Shim JY (2012) Effects of Korean Red Ginseng on cardiovascular risks in subjects with metabolic syndrome: a double-blind randomized controlled study. Korean J Fam Med 33:190–196. https://doi.org/10.4082/kjfm2012334190

    Article  PubMed  PubMed Central  Google Scholar 

  107. Rhee MY, Cho B, Kim KI, Kim J, Kim MK, Lee EK, Kim HJ, Kim CH (2014) Blood pressure lowering effect of Korea ginseng derived ginseol K-g1. Am J Chin Med 42:605–618. https://doi.org/10.1142/S0192415X14500396

    Article  CAS  PubMed  Google Scholar 

  108. Stavro PM, Woo M, Heim TF, Leiter LA, Vuksan V (2005) North American ginseng exerts a neutral effect on blood pressure in individuals with hypertension. Hypertension 46:406–411

    CAS  PubMed  Google Scholar 

  109. Stavro PM, Woo M, Leiter LA, Heim TF, Sievenpiper JL, Vuksan V (2006) Long-term intake of North American ginseng has no effect on 24-hour blood pressure and renal function. Hypertension 47:791–796

    CAS  PubMed  Google Scholar 

  110. Mucalo I, Jovanovski E, Rahelić D, Božikov V, Romić Z, Vuksan V (2013) Effect of American ginseng (Panax quinquefolius L) on arterial stiffness in subjects with type-2 diabetes and concomitant hypertension. J Ethnopharmacol 150:148–153. https://doi.org/10.1016/jjep201308015

    Article  CAS  PubMed  Google Scholar 

  111. Rhee MY, Kim YS, Bae JH, Nah DY, Kim YK, Lee MM, Kim HY (2011) Effect of Korean red ginseng on arterial stiffness in subjects with hypertension. J Altern Complement Med 17:45–49. https://doi.org/10.1089/acm20100065

    Article  PubMed  Google Scholar 

  112. Jovanovski E, Lea-Duvnjak-Smircic KA, Au-Yeung F, Zurbau A, Jenkins AL, Sung MK, Josse R, Vuksan V (2020) Vascular effects of combined enriched Korean Red ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) administration in individuals with hypertension and type 2 diabetes: a randomized controlled trial. Complement Ther Med 49:102338. https://doi.org/10.1016/j.ctim.2020.102338

    Article  PubMed  Google Scholar 

  113. Mohanan P, Subramaniyam S, Mathiyalagan R, Yang DC (2018) Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions. J Ginseng Res 4:123–132. https://doi.org/10.1016/jjgr201701008

    Article  Google Scholar 

  114. Li Z, Chen X, Niwa Y, Sakamoto S, Nakaya Y (2001) Involvement of Ca2+-activated K+ channels in ginsenosides-induced aortic relaxation in rats. J Cardiovasc Pharmacol 37:41–47

    CAS  PubMed  Google Scholar 

  115. Toda N, Ayajiki K, Fujioka H, Okamura T (2001) Ginsenoside potentiates NO-mediated neurogenic vasodilatation of monkey cerebral arteries. J Ethnopharmacol 76:109–113

    CAS  PubMed  Google Scholar 

  116. Kim ND, Kim EM, Kang KW, Cho MK, Choi SY, Kim SG (2003) Ginsenoside Rg3 inhibits phenylephrine-induced vascular contraction through induction of nitric oxide synthase. Br J Pharmacol 140:661–670

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Kim ND, Kang SY, Park JH, Schini-Kerth VB (1999) Ginsenoside Rg3 mediates endothelium-dependent relaxation in response to ginsenosides in rat aorta: role of K+ channels. Eur J Pharmacol 367:41–49

    CAS  PubMed  Google Scholar 

  118. Kim ND, Kang SY, Kim MJ, Park JH, Schini-Kerth VB (1999) The ginsenoside Rg3 evokes endothelium-independent relaxation in rat aortic rings: role of K+ channels. Eur J Pharmacol 367:51–57

    CAS  PubMed  Google Scholar 

  119. Dong DL, Bai YL, Cai BZ (2016) Calcium-activated potassium channels: potential target for cardiovascular diseases. Adv Protein Chem Struct Biol 104:233–261. https://doi.org/10.1016/bsapcsb201511007

    Article  CAS  PubMed  Google Scholar 

  120. Nakaya Y, Mawatari K, Takahashi A, Harada N, Hata A, Yasui S (2007) The phytoestrogen ginsensoside Re activates potassium channels of vascular smooth muscle cells through PI3K/Akt and nitric oxide pathways. J Med Investig 54:381–384

    Google Scholar 

  121. Archer SL, Huang JM, Hampl V, Nelson DP, Shultz PJ, Weir EK (1994) Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci USA 91:7583–7587

    CAS  PubMed  Google Scholar 

  122. Yu J, Eto M, Akishita M, Kaneko A, Ouchi Y, Okabe T (2007) Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor. Biochem Biophys Res Commun 353:764–769. Erratum in: Biochem Biophys Res Commun (2007) 355:597

  123. Shin W, Yoon J, Oh GT, Ryoo S (2013) Korean red ginseng inhibits arginase and contributes to endothelium dependent vasorelaxation through endothelial nitric oxide synthase coupling. J Ginseng Res 37:64–73. https://doi.org/10.5142/jgr20133764

    Article  PubMed  PubMed Central  Google Scholar 

  124. Shen K, Leung SW, Ji L, Huang Y, Hou M, Xu A, Wang Z, Vanhoutte PM (2014) Notoginsenoside Ft1 activates both glucocorticoid and estrogen receptors to induce endothelium-dependent, nitric oxide-mediated relaxations in rat mesenteric arteries. Biochem Pharmacol 88:66–74. https://doi.org/10.1016/jbcp201401007

    Article  CAS  PubMed  Google Scholar 

  125. Wang RX, He RL, Jiao HX, Dai M, Mu YP, Hu Y, Wu ZJ, Sham JS, Lin MJ (2015) Ginsenoside Rb1 attenuates agonist-induced contractile response via inhibition of store-operated calcium entry in pulmonary arteries of normal and pulmonary hypertensive rats. Cell Physiol Biochem 35:1467–1481. https://doi.org/10.1159/000373966

    Article  CAS  PubMed  Google Scholar 

  126. Xu Y, Lin L, Tang L, Zheng M, Ma Y, Huang L, Meng W, Wang W (2014) Notoginsenoside R1 attenuates hypoxia and hypercapnia-induced vasoconstriction in isolated rat pulmonary arterial rings by reducing the expression of ERK. Am J Chin Med 42:799–816. https://doi.org/10.1142/S0192415X14500517

    Article  CAS  PubMed  Google Scholar 

  127. Persson IA, Dong L, Persson K (2006) Effect of Panax ginseng extract (G115) on angiotensin-converting enzyme (ACE) activity and nitric oxide (NO) production. J Ethnopharmacol 105:321–325

    PubMed  Google Scholar 

  128. Guan YY, Zhou JG, Zhang Z, Wang GL, Cai BX, Hong L, Qiu QY, He H (2006) Ginsenoside-Rd from panax notoginseng blocks Ca2+ influx through receptor- and store-operated Ca2+ channels in vascular smooth muscle cells. Eur J Pharmacol 548:129–136

    CAS  PubMed  Google Scholar 

  129. Wang Y, Dong J, Liu P, Lau CW, Gao Z, Zhou D, Tang J, Ng CF, Huang Y (2014) Ginsenoside Rb3 attenuates oxidative stress and preserves endothelial function in renal arteries from hypertensive rats. Br J Pharmacol 171:3171–3181. https://doi.org/10.1111/bph12660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Wang Y, Ren Y, Xing L, Dai X, Liu S, Yu B, Wang Y (2016) Endothelium-dependent vasodilation effects of Panax notoginseng and its main components are mediated by nitric oxide and cyclooxygenase pathways. Exp Ther Med 12:3998–4006. https://doi.org/10.3892/etm20163890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Park HR, Lee SE, Yang H, Son GW, Jin YH, Park YS (2015) Induction of thioredoxin reductase 1 by Korean red ginseng water extract regulates cytoprotective effects on human endothelial cells. Evid Based Complement Alternat Med 2015:972040. https://doi.org/10.1155/2015/972040

    Article  PubMed  PubMed Central  Google Scholar 

  132. Gupta YK, Dahiya AK, Reeta KH (2010) Gaso-transmitter hydrogen sulphide: potential new target in pharmacotherapy. Indian J Exp Biol 48:1069–1077

    CAS  PubMed  Google Scholar 

  133. Bełtowski J, Jamroz-Wiśniewska A (2014) A Hydrogen sulfide and endothelium-dependent vasorelaxation. Molecules 19:21183–21199. https://doi.org/10.3390/molecules191221183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Lee JY, Lim KM, Kim SY, Bae ON, Noh JY, Chung SM, Kim K, Shin YS, Lee MY, Chung JH (2010) Vascular smooth muscle dysfunction and remodeling induced by ginsenoside Rg3, a bioactive component of ginseng. Toxicol Sci 117:505–514. https://doi.org/10.1093/toxsci/kfq201

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Morris Karmazyn.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Morris Karmazyn and Xiaohong Tracey Gan have retired.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karmazyn, M., Gan, X.T. Chemical components of ginseng, their biotransformation products and their potential as treatment of hypertension. Mol Cell Biochem 476, 333–347 (2021). https://doi.org/10.1007/s11010-020-03910-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-020-03910-8

Keywords

Navigation