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Examination of the Pharmacokinetics of Active Ingredients of Ginger in Humans

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Abstract

Ginger extracts have been studied in various clinical trials for different indications. However, the pharmacokinetics of the ginger active constituents in human biological matrices is not well investigated. This study aims to develop a LC-MS/MS method for simultaneous measurement of 6-, 8-, and 10-gingerols and 6-shogaol and study their pharmacokinetics in human plasma and colon tissues. A sensitive LC-MS/MS method was established and validated with a low limit of quantification of 2–5 ng/mL. The intra- and inter-day accuracy ranged from −7.3% to 10.4% and from −9.4% to 9.8%, respectively. The intra- and inter-day precision ranged from 0.9% to 10.9% and from 2.0% to 12.4%, respectively. The glucuronide and sulfate metabolites of 6-, 8-, and 10-gingerols and 6-shogaol in plasma and colon tissues were quantified after hydrolysis with β-glucuronidase and sulfatase. After oral dosing of 2.0 g ginger extracts in human, free 10-gingerol and 6-shogaol were detected in plasma with peak concentrations (9.5 ± 2.2 and 13.6 ± 6.9 ng/mL, respectively) at 1 h after oral administration, but no free 6-gingerol and 8-gingerol were detected in plasma from 0.25 to 24 h. The peak concentrations of glucuronide metabolites of 6-, 8-, and 10-gingerols and 6-shogaol were 0.47 ± 0.31, 0.17 ± 0.14, 0.37 ± 0.19, and 0.73 ± 0.54 μg/mL at 1 h, respectively. The peak concentrations of the sulfate metabolites of 6-, 8-, and 10-gingerols and 6-shogaol were 0.28 ± 0.15, 0.027 ± 0.018, 0.018 ± 0.006, and 0.047 ± 0.035 μg/mL at 1 h, respectively. Very low concentrations (2–3 ng/mL) of 10-gingerol glucuronide and sulfate were found in colon tissues. Pharmacokinetic analysis showed that half-lives of these four analytes and their metabolites were 1–3 h in human plasma. No accumulation was observed for 6-, 8-, and 10-gingerols and 6-shogaol and their metabolites in both plasma and colon tissues after multiple daily dosing.

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References

  1. Zick SM, Djuric Z, Ruffin MT, Litzinger AJ, Normolle DP, Alrawi S, et al. Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev. 2008;17(8):1930–6.

    Article  PubMed  CAS  Google Scholar 

  2. Kawai T, Kinoshita K, Koyama K, Takahashi K. Anti-emetic principles of Magnolia obovata bark and Zingiber officinale rhizome. Planta Med. 1994;60(1):17–20.

    Article  PubMed  CAS  Google Scholar 

  3. Wang W, Li CY, Wen XD, Li P, Qi LW. Simultaneous determination of 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol in rat plasma by liquid chromatography–mass spectrometry: application to pharmacokinetics. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877(8–9):671–9.

    PubMed  CAS  Google Scholar 

  4. Shukla Y, Singh M. Cancer preventive properties of ginger: a brief review. Food Chem Toxicol. 2007;45(5):683–90.

    Article  PubMed  CAS  Google Scholar 

  5. Surh YJ. Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review. Food Chem Toxicol. 2002;40(8):1091–7.

    Article  PubMed  CAS  Google Scholar 

  6. Alizadeh-Navaei R, Roozbeh F, Saravi M, Pouramir M, Jalali F, Moghadamnia AA. Investigation of the effect of ginger on the lipid levels. A double blind controlled clinical trial. Saudi Med J. 2008;29(9):1280–4.

    PubMed  Google Scholar 

  7. Schwertner HA, Rios DC, Pascoe JE. Variation in concentration and labeling of ginger root dietary supplements. Obstet Gynecol. 2006;107(6):1337–43.

    Article  PubMed  CAS  Google Scholar 

  8. Tao Y, Li W, Liang W, Van Breemen RB. Identification and quantification of gingerols and related compounds in ginger dietary supplements using high-performance liquid chromatography–tandem mass spectrometry. J Agric Food Chem. 2009;57(21):10014–21.

    Article  PubMed  CAS  Google Scholar 

  9. Apariman S, Ratchanon S, Wiriyasirivej B. Effectiveness of ginger for prevention of nausea and vomiting after gynecological laparoscopy. J Med Assoc Thai. 2006;89(12):2003–9.

    PubMed  Google Scholar 

  10. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai. 2007;90(1):15–20.

    PubMed  Google Scholar 

  11. Hickok JT, Roscoe JA, Morrow GR, Ryan JL. A phase II/III randomized, placebo-controlled, double-blind clinical trial of ginger (Zingiber officinale) for nausea caused by chemotherapy for cancer: a currently accruing URCC CCOP Cancer Control Study. Support Cancer Ther. 2007;4(4):247–50.

    Article  PubMed  Google Scholar 

  12. Ozgoli G, Goli M, Moattar F. Comparison of effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea. J Altern Complement Med. 2009;15:129–32.

    Article  PubMed  Google Scholar 

  13. Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S, Leeprakobboon K, Leelasettagool C. The efficacy of ginger for the prevention of postoperative nausea and vomiting: a meta-analysis. Am J Obstet Gynecol. 2006;194(1):95–9.

    Article  PubMed  Google Scholar 

  14. Betz O, Kranke P, Geldner G, Wulf H, Eberhart LH. Is ginger a clinically relevant antiemetic? A systematic review of randomized controlled trials. Forsch Komplementarmed Klass Naturheilkd. 2005;12(1):14–23.

    Article  PubMed  Google Scholar 

  15. Bliddal H, Rosetzsky A, Schlichting P, Weidner MS, Andersen LA, Ibfelt HH, et al. A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis. Osteoarthritis Cartilage. 2000;8(1):9–12.

    Article  PubMed  CAS  Google Scholar 

  16. Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum. 2001;44(11):2531–8.

    Article  PubMed  CAS  Google Scholar 

  17. Govindarajan VS. Ginger–chemistry, technology, and quality evaluation: part 1. Crit Rev Food Sci Nutr. 1982;17(1):1–96.

    Article  PubMed  CAS  Google Scholar 

  18. Govindarajan VS. Ginger-chemistry, technology, and quality evaluation: part 2. Crit Rev Food Sci Nutr. 1982;17(3):189–258.

    Article  PubMed  CAS  Google Scholar 

  19. Sang S, Hong J, Wu H, Liu J, Yang CS, Pan MH, et al. Increased growth inhibitory effects on human cancer cells and anti-inflammatory potency of shogaols from Zingiber officinale relative to gingerols. J Agric Food Chem. 2009;57(22):10645–50.

    Article  PubMed  CAS  Google Scholar 

  20. Wu H, Hsieh MC, Lo CY, Liu CB, Sang S, Ho CT, et al. 6-Shogaol is more effective than 6-gingerol and curcumin in inhibiting 12-O-tetradecanoylphorbol 13-acetate-induced tumor promotion in mice. Mol Nutr Food Res. 2010;54:1296–306.

    Article  PubMed  CAS  Google Scholar 

  21. Mascolo N, Jain R, Jain SC, Capasso F. Ethnopharmacologic investigation of ginger (Zingiber officinale). J Ethnopharmacol. 1989;27(1–2):129–40.

    Article  PubMed  CAS  Google Scholar 

  22. Kim EC, Min JK, Kim TY, Lee SJ, Yang HO, Han S, et al. [6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo. Biochem Biophys Res Commun. 2005;335(2):300–8.

    Article  PubMed  CAS  Google Scholar 

  23. Yagihashi S, Miura Y, Yagasaki K. Inhibitory effect of gingerol on the proliferation and invasion of hepatoma cells in culture. Cytotechnology. 2008;57(2):129–36.

    Article  PubMed  CAS  Google Scholar 

  24. Lee TY, Lee KC, Chen SY, Chang HH. 6-Gingerol inhibits ROS and iNOS through the suppression of PKC-alpha and NF-kappaB pathways in lipopolysaccharide-stimulated mouse macrophages. Biochem Biophys Res Commun. 2009;382(1):134–9.

    Article  PubMed  CAS  Google Scholar 

  25. Akoachere JF, Ndip RN, Chenwi EB, Ndip LM, Njock TE, Anong DN. Antibacterial effect of Zingiber officinale and Garcinia kola on respiratory tract pathogens. East Afr Med J. 2002;79(11):588–92.

    PubMed  CAS  Google Scholar 

  26. Ficker C, Smith ML, Akpagana K, Gbeassor M, Zhang J, Durst T, et al. Bioassay-guided isolation and identification of antifungal compounds from ginger. Phytother Res. 2003;17(8):897–902.

    Article  PubMed  CAS  Google Scholar 

  27. Park M, Bae J, Lee DS. Antibacterial activity of [10]-gingerol and [12]-gingerol isolated from ginger rhizome against periodontal bacteria. Phytother Res. 2008;22(11):1446–9.

    Article  PubMed  CAS  Google Scholar 

  28. Jeong CH, Bode AM, Pugliese A, Cho YY, Kim HG, Shim JH, et al. [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase. Cancer Res. 2009;69(13):5584–91.

    Article  PubMed  CAS  Google Scholar 

  29. Dugasani S, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN. Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol. J Ethnopharmacol. 2010;127(2):515–20.

    Article  PubMed  CAS  Google Scholar 

  30. Asai A, Miyazawa T. Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma. Life Sci. 2000;67(23):2785–93.

    Article  PubMed  CAS  Google Scholar 

  31. Jiang SZ, Wang NS, Mi SQ. Plasma pharmacokinetics and tissue distribution of [6]-gingerol in rats. Biopharm Drug Dispos. 2008;29(9):529–37.

    Article  PubMed  CAS  Google Scholar 

  32. Wang W, Li CY, Wen XD, Li P, Qi LW. Plasma pharmacokinetics, tissue distribution and excretion study of 6-gingerol in rat by liquid chromatography–electrospray ionization time-of-flight mass spectrometry. J Pharm Biomed Anal. 2009;49(4):1070–4.

    Article  PubMed  CAS  Google Scholar 

  33. Bhattarai S, Tran VH, Duke CC. Stability of [6]-gingerol and [6]-shogaol in simulated gastric and intestinal fluids. J Pharm Biomed Anal. 2007;45(4):648–53.

    Article  PubMed  CAS  Google Scholar 

  34. Rhode J, Fogoros S, Zick S, Wahl H, Griffith KA, Huang J, et al. Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells. BMC Complement Altern Med. 2007;7:44.

    Article  PubMed  Google Scholar 

  35. Aktan F, Henness S, Tran VH, Duke CC, Roufogalis BD, Ammit AJ. Gingerol metabolite and a synthetic analogue Capsarol inhibit macrophage NF-kappaB-mediated iNOS gene expression and enzyme activity. Planta Med. 2006;72(8):727–34.

    Article  PubMed  CAS  Google Scholar 

  36. Tjendraputra E, Tran VH, Liu-Brennan D, Roufogalis BD, Duke CC. Effect of ginger constituents and synthetic analogues on cyclooxygenase-2 enzyme in intact cells. Bioorg Chem. 2001;29(3):156–63.

    Article  PubMed  CAS  Google Scholar 

  37. Chung WY, Jung YJ, Surh YJ, Lee SS, Park KK. Antioxidative and antitumor promoting effects of [6]-paradol and its homologs. Mutat Res. 2001;496(1–2):199–206.

    PubMed  CAS  Google Scholar 

  38. Nurtjahja-Tjendraputra E, Ammit AJ, Roufogalis BD, Tran VH, Duke CC. Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger. Thromb Res. 2003;111(4–5):259–65.

    Article  PubMed  CAS  Google Scholar 

  39. Oyagbemi AA, Saba AB, Azeez OI. Molecular targets of [6]-gingerol: its potential roles in cancer chemoprevention. Biofactors. 2010;36(3):169–78.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was partially supported by the National Institutes of Health (RO1 CA120023 and R21 CA143474 to DS); National Cancer Institute (P30 CA48592 and K07 CA102592 to SZ); University of Michigan Clinical Research Center UL1RR024986; University of Michigan Cancer Center Research Grant (Munn); and University of Michigan Cancer Center Core Grant.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, The University of Michigan, Room 2020, 428 Church Street, Ann Arbor, Michigan, 48109-1065, USA

    Yanke Yu, Xiaoqin Li, Peng Zou & Duxin Sun

  2. Department of Family Medicine, Internal Medicine, University of Michigan, 24 Frank Lloyd Wright Drive, Ann Arbor, Michigan, 48105, USA

    Suzanna Zick & Benjamin Wright

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  1. Yanke Yu
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  2. Suzanna Zick
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Correspondence to Suzanna Zick or Duxin Sun.

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Yu, Y., Zick, S., Li, X. et al. Examination of the Pharmacokinetics of Active Ingredients of Ginger in Humans. AAPS J 13, 417–426 (2011). https://doi.org/10.1208/s12248-011-9286-5

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