Skip to main content
SpringerLink
Log in

In vivo metabolism study of ginsenoside Re in rat using high-performance liquid chromatography coupled with tandem mass spectrometry

  • Original Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Ginsenoside Re is one of the major the bioactive triterpene saponins in ginseng root, a well-known adaptogen in traditional Chinese medicine. It is believed that the lead compound may be further developed into a promising new drug for preventing hypertension and cardiovascular disease. To better understand the pharmacological activities of the component, an investigation of its in vivo metabolism was necessary. In the present study, a high-performance liquid chromatography coupled with electrospray ionization and quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-TOF-MS/MS) has been applied to discover and identify the metabolites of ginsenoside Re in rat urine following intravenous and oral administration of the component, respectively. The rat urine samples were collected and pretreated through C18 solid-phase extraction cartridges prior to analysis. Negative electrospray ionization mass spectrometry was used to discern ginsenoside Re and its possible metabolites in urine samples. The metabolites were identified and tentatively characterized by means of comparing molecular mass, retention time, and fragmentation pattern of the analytes with those of the parent compound, ginsenoside Re. As a result, eleven and nine metabolites together with Re were detected and identified in rat urine collected after intravenous and oral administration, respectively. A possible metabolic pathway of ginsenoside Re was also investigated and proposed. Oxidation and deglycosylation were found to be the major metabolic processes of the constituent in rat.

Proposed metabolic pathways of 20(S)-ginsenoside Re in rats.

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

Access this article

Log in via an institution

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Block KI, Mead MN (2003) Immune system effects of echinacea, ginseng, and astragalus: a review. Integr Cancer Ther 2:247–267

    Article  Google Scholar 

  2. Elam JL, Carpenter JS, Shu XO, Boyapati S, Friedmann-Gilchrist J (2006) Methodological issues in the investigation of ginseng as an intervention for fatigue. Clin Nurse Spec 20:183–189

    Article  Google Scholar 

  3. Chang YS, Seo EK, Gyllenhaal C, Block KI (2003) Panax ginseng: a role in cancer therapy? Integr Cancer Ther 2:13–33

    Article  CAS  Google Scholar 

  4. Hasegawa H, Suzuki R, Nagaoka T, Tezuka Y, Kadota S, Saiki I (2002) Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatriol. Biol Pharm Bull 25:861–866

    Article  CAS  Google Scholar 

  5. Wang CZ, Yuan CS (2008) Potential role of ginseng in the treatment of colorectal cancer. Am J Chin Med 36:1019–1028

    Article  CAS  Google Scholar 

  6. Metori K, Furutsu M, Takahashi S (1997) The preventive effect of ginseng with du-zhong leaf on protein metabolism in aging. Biol Pharm Bull 20:237–242

    CAS  Google Scholar 

  7. Wang YG, Zima AV, Ji X, Pabbidi R, Blatter LA, Lipsius SL (2008) Ginsenoside Re suppresses electromechanical alternans in cat and human cardiomyocytes. Am J Physiol Heart Circ Physiol 295:H851–H859

    Article  CAS  Google Scholar 

  8. 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

    Article  Google Scholar 

  9. Leung KW, Leung FP, Huang Y, Mak NK, Wong RN (2007) Non-genomic effects of ginsenoside-Re in endothelial cells via glucocorticoid receptor. FEBS Lett 581:2423–2428

    Article  CAS  Google Scholar 

  10. Zhou XM, Cao YL, Dou DQ (2006) Protective effect of ginsenoside-Re against cerebral ischemia/reperfusion damage in rats. Biol Pharm Bull 29:2502–2505

    Article  CAS  Google Scholar 

  11. Cho WC, Chung WS, Lee SK, Leung AW, Cheng CH, Yue KK (2006) Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats. Eur J Pharmacol 550:173–179

    Article  CAS  Google Scholar 

  12. Bai CX, Takahashi K, Masumiya H, Sawanobori T, Furukawa T (2004) Nitric oxide-dependent modulation of the delayed rectifier K+ current and the L-type Ca2+ current by ginsenoside Re, an ingredient of Panax ginseng, in guinea-pig cardiomyocytes. Br J Pharmacol 142:567–575

    Article  CAS  Google Scholar 

  13. Liu Z, Li Z, Liu X (2002) Effect of ginsenoside Re on cardiomyocyte apoptosis and expression of Bcl-2/Bax gene after ischemia and reperfusion in rats. J Huazhong Univ Sci Technol Med Sci 22:305–309

    Google Scholar 

  14. Chen CX, Zhang HY (2009) Protective effect of ginsenoside Re on isoproterenol-induced triggered ventricular arrhythmia in rabbits. Chin J Contemp Pediatr 11:384–388

    Google Scholar 

  15. Jin ZQ, Liu CM (1994) Effect of ginsenoside Re on the electrophysiological activity of the heart. Planta Med 60:192–193

    Article  CAS  Google Scholar 

  16. Kim SN, Ha YW, Shin H, Son SH, Wu SJ, Kim YS (2007) Simultaneous quantification of 14 ginsenosides in Panax ginseng C.A. Meyer (Korean red ginseng) by HPLC-ELSD and its application to quality control. J Pharm Biomed Anal 45:164–170

    Article  CAS  Google Scholar 

  17. Morinaga O, Tanaka H, Shoyama Y (2006) Detection and quantification of ginsenoside Re in ginseng samples by a chromatographic immunostaining method using monoclonal antibody against ginsenoside Re. J Chromatogr B 830:100–104

    Article  CAS  Google Scholar 

  18. Liu YM, Yang L, Zeng X, Deng YH, Feng Y, Liang WX (2005) Pharmacokinetics of ginsenosides Rg1 and Re in Shenmai injection. Acta Pharm Sin 40:365–368

    Google Scholar 

  19. Luchtefeld R, Kostoryz E, Smith RE (2004) Determination of ginsenosides Rb1, Rc, and Re in different dosage forms of ginseng by negative ion electrospray liquid chromatography-mass spectrometry. J Agric Food Chem 52:4953–4956

    Article  CAS  Google Scholar 

  20. Cai Z, Lee FSC, Wang XR, Yu WJ (2002) A capsule review of recent studies on the application of mass spectrometry in the analysis of Chinese medicinal herbs. J Mass Spectrom 37:1013–1024

    Article  CAS  Google Scholar 

  21. Lee J, Lee E, Kim D, Lee J, Yoo J, Koh B (2009) Studies on absorption, distribution and metabolism of ginseng in humans after oral administration. J Ethnopharmacol 122:143–148

    Article  CAS  Google Scholar 

  22. Yang L, Deng YH, Xu SJ, Zeng X (2007) In vivo pharmacokinetic and metabolism studies of ginsenoside Rd. J Chromatogr B 854:77–84

    Article  CAS  Google Scholar 

  23. 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

    Article  Google Scholar 

  24. Yang L, Xu SJ, Zeng X, Wu ZF, Deng YH, Liu YM, Deng SG, Ou RM (2006) In vivo rat metabolism studies of ginsenoside Rb1. Chem J Chin Univ 27:1042–1044

    CAS  Google Scholar 

  25. Bae EA, Han MJ, Choo MK, Park SY, Kim DH (2002) Metabolism of 20(S)- and 20(R)-ginsenoside Rg3 by human intestinal bacteria and its relation to in vitro biological activities. Biol Pharm Bull 25:58–63

    Article  CAS  Google Scholar 

  26. Wang Y, Wang BX, Liu TH, Minami M, Nagata T, Ikejima T (2000) Metabolism of ginsenoside Rg1 by intestinal bacteria. II. Immunological activity of ginsenoside Rg1 and Rh1. Acta Pharmacol Sin 21:792–796

    CAS  Google Scholar 

  27. Holcapek M, Kolarova L, Nobilis M (2008) High-performance liquid chromatography-tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites. Anal Bioanal Chem 391:59–78

    Article  CAS  Google Scholar 

  28. Suchanova B, Kostiainen R, Ketola RA (2008) Characterization of the in vitro metabolic profile of amlodipine in rat using liquid chromatography-mass spectrometry. Eur J Pharm Sci 33:91–99

    CAS  Google Scholar 

  29. Tong W, Chowdhury SK, Su AD, Feng W, Ghosal A, Alton KB (2006) Identification of unstable metabolites of Lonafarnib using liquid chromatography-quadrupole time-of-flight mass spectrometry, stable isotope incorporation and ion source temperature alteration. J Mass Spectrom 41:1430–1441

    Article  CAS  Google Scholar 

  30. Dasandi B, Shah S, Shivprakash (2009) Development and validation of a high throughput and robust LC-MS/MS with electrospray ionization method for simultaneous quantitation of diltiazem and its two metabolites in human plasma: application to a bioequivalence study. J Chromatogr B 877:791–798

    Article  CAS  Google Scholar 

  31. Prasaja B, Sasongko L, Harahap Y, Hardiyanti LW, Grigg M (2009) Simultaneous quantification of losartan and active metabolite in human plasma by liquid chromatography-tandem mass spectrometry using irbesartan as internal standard. J Pharm Biomed Anal 49:862–867

    Article  CAS  Google Scholar 

  32. Guo WF, Pan SY, Li CS, Ye GM, Li LY (2005) Separation of 20(S)-and 20(R)-ginsenoside Rg2 using HPLC. Chin J Public Health Eng 4:361–366

    Google Scholar 

  33. Dong HB, Pan SY, Wu P, Zhang M, Li CS (2003) The content determination simultaneously of isomer 20(S)- and 20(R)-ginsenoside Rg2 in Xinmaisu Injection by Rp-HPLC. Spec Wild Econ Anim Plant Res 25(3):47–49

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China

    Liu Yang & Zhijun Su

  2. Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, 999078, China

    Shunjun Xu

  3. Zhejiang Chinese Medical University, Hangzhou, 310053, China

    Chunjin Liu

Authors
  1. Liu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shunjun Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chunjin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhijun Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shunjun Xu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, L., Xu, S., Liu, C. et al. In vivo metabolism study of ginsenoside Re in rat using high-performance liquid chromatography coupled with tandem mass spectrometry. Anal Bioanal Chem 395, 1441–1451 (2009). https://doi.org/10.1007/s00216-009-3121-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-009-3121-1

Keywords

Search

Navigation