About this Journal Submit a Manuscript Table of Contents
Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 516870, 10 pages
http://dx.doi.org/10.1155/2012/516870
Review Article

Preventive and Protective Properties of Zingiber officinale (Ginger) in Diabetes Mellitus, Diabetic Complications, and Associated Lipid and Other Metabolic Disorders: A Brief Review

Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia

Received 16 August 2012; Accepted 21 October 2012

Academic Editor: I-Min Liu

Copyright © 2012 Yiming Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. Danaei, M. M. Finucane, Y. Lu et al., “National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants,” The Lancet, vol. 378, no. 9785, pp. 31–40, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. J. E. Shaw, R. A. Sicree, and P. Z. Zimmet, “Global estimates of the prevalence of diabetes for 2010 and 2030,” Diabetes Research and Clinical Practice, vol. 87, no. 1, pp. 4–14, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. K. G. M. M. Alberti and P. Z. Zimmet, “Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation,” Diabetic Medicine, vol. 15, no. 7, pp. 539–553, 1998. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Parillo and G. Riccardi, “Diet composition and the risk of type 2 diabetes: epidemiological and clinical evidence,” British Journal of Nutrition, vol. 92, no. 1, pp. 7–19, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. “Diagnosis and classification of diabetes mellitus,” Diabetes Care, vol. 35, supplement 1, pp. S64–S71, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. K. K. Ray, S. R. K. Seshasai, S. Wijesuriya et al., “Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials,” The Lancet, vol. 373, no. 9677, pp. 1765–1772, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. R. R. Holman, S. K. Paul, M. A. Bethel, D. R. Matthews, and H. A. W. Neil, “10-Year follow-up of intensive glucose control in type 2 diabetes,” The New England Journal of Medicine, vol. 359, no. 15, pp. 1577–1589, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. F. Ismail-Beigi, T. Craven, M. A. Banerji et al., “Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial,” The Lancet, vol. 376, no. 9739, pp. 419–430, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. B. White, “Ginger: an overview,” American Family Physician, vol. 75, no. 11, pp. 1689–1691, 2007. View at Scopus
  10. W. H. Wang and Z. M. Wang, “Studies of commonly used traditional medicine-ginger,” Zhongguo Zhongyao Zazhi, vol. 30, no. 20, pp. 1569–1573, 2005. View at Scopus
  11. S. Chrubasik, M. H. Pittler, and B. D. Roufogalis, “Zingiberis rhizoma: a comprehensive review on the ginger effect and efficacy profiles,” Phytomedicine, vol. 12, no. 9, pp. 684–701, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. B. H. Ali, G. Blunden, M. O. Tanira, and A. Nemmar, “Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research,” Food and Chemical Toxicology, vol. 46, no. 2, pp. 409–420, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. J. A. O. Ojewole, “Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats,” Phytotherapy Research, vol. 20, no. 9, pp. 764–772, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. S. P. Akhani, S. L. Vishwakarma, and R. K. Goyal, “Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats,” Journal of Pharmacy and Pharmacology, vol. 56, no. 1, pp. 101–105, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. Z. M. Al-Amin, M. Thomson, K. K. Al-Qattan, and M. Ali, “Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats,” British Journal of Nutrition, vol. 96, no. 4, pp. 660–666, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. N. B. Abdulrazaq, M. M. Cho, N. N. Win, R. Zaman, and M. T. Rahman, “Beneficial effects of ginger (Zingiber officinale) on carbohydrate metabolism in streptozotocin-induced diabetic rats,” British Journal of Nutrition, vol. 108, no. 07, pp. 1194–1201, 2011.
  17. R. H. Eckel, S. M. Grundy, and P. Z. Zimmet, “The metabolic syndrome,” The Lancet, vol. 365, no. 9468, pp. 1415–1428, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Nammi, S. Sreemantula, and B. D. Roufogalis, “Protective effects of ethanolic extract of Zingiber officinale rhizome on the development of metabolic syndrome in high-fat diet-fed rats,” Basic and Clinical Pharmacology and Toxicology, vol. 104, no. 5, pp. 366–373, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. H. R. Madkor, S. W. Mansour, and G. Ramadan, “Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats,” British Journal of Nutrition, vol. 105, no. 08, pp. 1210–1217, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. M. S. Islam and H. Choi, “Comparative effects of dietary ginger (Zingiber officinale) and garlic (Allium sativum) investigated in a type 2 diabetes model of rats,” Journal of Medicinal Food, vol. 11, no. 1, pp. 152–159, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. A. B. Singh, Akanksha, N. Singh, R. Maurya, and A. K. Srivastava, “Anti-hyperglycaemic, lipid lowering and anti-oxidant properties of [6]-gingerol in db/db mice,” International Journal of Medicine and Medical Sciences, vol. 1, no. 12, pp. 536–544, 2009.
  22. M. S. Weidner and K. Sigwart, “The safety of a ginger extract in the rat,” Journal of Ethnopharmacology, vol. 73, no. 3, pp. 513–520, 2000. View at Publisher · View at Google Scholar · View at Scopus
  23. M. P. Rani, M. S. Krishna, K. P. Padmakumari, K. G. Raghu, and A. Sundaresan, “Zingiber officinale extract exhibits antidiabetic potential via modulating glucose uptake, protein glycation and inhibiting adipocyte differentiation: an in vitro study,” Journal of the Science of Food and Agriculture, vol. 92, no. 9, pp. 1948–1955, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. Li, V. H. Tran, C. C. Duke, and B. D. Roufogalis, “Gingerols of Zingiber officinale enhance glucose uptake by increasing cell surface GLUT4 in cultured L6 myotubes,” Planta Medica, vol. 78, no. 14, pp. 1549–1555, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Sekiya, A. Ohtani, and S. Kusano, “Enhancement of insulin sensitivity in adipocytes by ginger,” BioFactors, vol. 22, no. 1–4, pp. 153–156, 2004. View at Scopus
  26. B. Andallu, B. Radhika, and V. Suryakantham, “Effect of aswagandha, ginger and mulberry on hyperglycemia and hyperlipidemia,” Plant Foods for Human Nutrition, vol. 58, no. 3, pp. 1–7, 2003. View at Scopus
  27. A. Bordia, S. K. Verma, and K. C. Srivastava, “Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 56, no. 5, pp. 379–384, 1997. View at Scopus
  28. S. D. Jolad, R. C. Lantz, J. C. Guan, R. B. Bates, and B. N. Timmermann, “Commercially processed dry ginger (Zingiber officinale): composition and effects on LPS-stimulated PGE2 production,” Phytochemistry, vol. 66, no. 13, pp. 1614–1635, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. S. D. Jolad, R. C. Lantz, A. M. Solyom, G. J. Chen, R. B. Bates, and B. N. Timmermann, “Fresh organically grown ginger (Zingiber officinale): composition and effects on LPS-induced PGE2 production,” Phytochemistry, vol. 65, no. 13, pp. 1937–1954, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Priya Rani, K. P. Padmakumari, B. Sankarikutty, O. Lijo Cherian, V. M. Nisha, and K. G. Raghu, “Inhibitory potential of ginger extracts against enzymes linked to type 2 diabetes, inflammation and induced oxidative stress,” International Journal of Food Sciences and Nutrition, vol. 62, no. 2, pp. 106–110, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. L. G. Ranilla, Y. I. Kwon, E. Apostolidis, and K. Shetty, “Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America,” Bioresource Technology, vol. 101, no. 12, pp. 4676–4689, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. K. Platel and K. Srinivasan, “Influence of dietary spices and their active principles on pancreatic digestive enzymes in albino rats,” Die Nahrung, vol. 44, no. 1, pp. 42–46, 2000. View at Scopus
  33. A. A. Rossini, A. A. Like, and W. L. Chick, “Studies of streptozotocin induced insulitis and diabetes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 74, no. 6, pp. 2485–2489, 1977. View at Scopus
  34. A. A. Like and A. A. Rossini, “Streptozotocin induced pancreatic insulitis: new model of diabetes mellitus,” Science, vol. 193, no. 4251, pp. 415–417, 1976. View at Scopus
  35. A. Junod, A. E. Lambert, W. Stauffacher, and A. E. Renold, “Diabetogenic action of streptozotocin: relationship of dose to metabolic response,” The Journal of Clinical Investigation, vol. 48, no. 11, pp. 2129–2139, 1969. View at Scopus
  36. D. Chakraborty, A. Mukherjee, S. Sikdar, A. Paul, S. Ghosh, and A. R. Khuda-Bukhsh, “[6]-Gingerol isolated from ginger attenuates sodium arsenite induced oxidative stress and plays a corrective role in improving insulin signaling in mice,” Toxicology Letters, vol. 210, no. 1, pp. 34–43, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. K. Heimes, B. Feistel, and E. J. Verspohl, “Impact of the 5-HT3 receptor channel system for insulin secretion and interaction of ginger extracts,” European Journal of Pharmacology, vol. 624, no. 1–3, pp. 58–65, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. H. Abdel-Aziz, T. Windeck, M. Ploch, and E. J. Verspohl, “Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum,” European Journal of Pharmacology, vol. 530, no. 1-2, pp. 136–143, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. K. Noipha, S. Ratanachaiyavong, and P. Ninla-aesong, “Enhancement of glucose transport by selected plant foods in muscle cell line L6,” Diabetes Research and Clinical Practice, vol. 89, no. 2, pp. e22–e26, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Denis McGarry, “Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes,” Diabetes, vol. 51, no. 1, pp. 7–18, 2002. View at Scopus
  41. P. J. Randle, P. B. Garland, C. N. Hales, and E. A. Newsholme, “The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus,” The Lancet, vol. 281, no. 7285, pp. 785–789, 1963. View at Scopus
  42. M. Roden, T. B. Price, G. Perseghin et al., “Mechanism of free fatty acid-induced insulin resistance in humans,” The Journal of Clinical Investigation, vol. 97, no. 12, pp. 2859–2865, 1996. View at Scopus
  43. R. I. Fink, P. Wallace, G. Brechtel, and J. M. Olefsky, “Evidence that glucose transport is rate-limiting for in vivo glucose uptake,” Metabolism, vol. 41, no. 8, pp. 897–902, 1992. View at Publisher · View at Google Scholar · View at Scopus
  44. P. Paranjpe, P. Patki, and B. Patwardhan, “Ayurvedic treatment of obesity: a randomised double-blind, placebo-controlled clinical trial,” Journal of Ethnopharmacology, vol. 29, no. 1, pp. 1–11, 1990. View at Scopus
  45. R. Kamal and S. Aleem, “Clinical evaluation of the efficacy of a combination of zanjabeel (Zingiber officinale) and amla (Emblica officinalis) in hyperlipidaemia,” Indian Journal of Traditional Knowledge, vol. 8, no. 3, pp. 413–416, 2009.
  46. S. Nammi, M. S. Kim, N. S. Gavande, G. Q. Li, and B. D. Roufogalis, “Regulation of low-density lipoprotein receptor and 3-hydroxy-3- methylglutaryl coenzyme A reductase expression by Zingiber officinale in the liver of high-fat diet-fed rats,” Basic and Clinical Pharmacology and Toxicology, vol. 106, no. 5, pp. 389–395, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. X.-H. Li, K. C.-Y. McGrath, S. Nammi, A. K. Heather, and B. D. Roufogalis, “Attenuation of liver pro-inflammatory responses by Zingiber officinale via inhibition of NF-kappa B activation in high-fat diet-fed rats,” Basic and Clinical Pharmacology and Toxicology, vol. 110, no. 3, pp. 238–244, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. K. R. Shanmugam, K. Mallikarjuna, K. Nishanth, C. H. Kuo, and K. S. Reddy, “Protective effect of dietary ginger on antioxidant enzymes and oxidative damage in experimental diabetic rat tissues,” Food Chemistry, vol. 124, no. 4, pp. 1436–1442, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. A. C. P. Reddy and B. R. Lokesh, “Studies on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes,” Molecular and Cellular Biochemistry, vol. 111, no. 1-2, pp. 117–124, 1992. View at Scopus
  50. K. R. Shanmugam, C. H. Ramakrishna, K. Mallikarjuna, and K. S. Reddy, “The impact of ginger on kidney carbohydrate metabolic profiles in STZ induced diabetic rats,” Asian Journal of Experimental Sciences, vol. 23, no. 1, pp. 127–134, 2009.
  51. S. K. Ramudu, M. Korivi, N. Kesireddy et al., “Nephro-protective effects of a ginger extract on cytosolic and mitochondrial enzymes against streptozotocin (STZ)-induced diabetic complications in rats,” The Chinese Journal of Physiology, vol. 54, no. 2, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. K. Al-Qattan, M. Thomson, and M. Ali, “Garlic (Allium sativum) and ginger (Zingiber officinale) attenuate structural nephropathy progression in streptozotocin-induced diabetic rats,” e-SPEN, vol. 3, no. 2, pp. e62–e71, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. E. S. M. Elrokh, N. A. Z. Yassin, S. M. A. El-Shenawy, and B. M. M. Ibrahim, “Antihypercholesterolaemic effect of ginger rhizome (Zingiber officinale) in rats,” Inflammopharmacology, vol. 18, no. 6, pp. 309–315, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Matsuda, Z. Wang, S. Takahashi, T. Tokuda, N. Miura, and J. Hasegawa, “Upregulation of mRNA of retinoid binding protein and fatty acid binding protein by cholesterol enriched-diet and effect of ginger on lipid metabolism,” Life Sciences, vol. 84, no. 25-26, pp. 903–907, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. D. A. York, S. Thomas, F. L. Greenway, Z. Liu, and J. C. Rood, “Effect of an herbal extract Number Ten (NT) on body weight in rats,” Chinese Medicine, vol. 2, article 10, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. R. K. Goyal and S. V. Kadnur, “Beneficial effects of Zingiber officinale on goldthioglucose induced obesity,” Fitoterapia, vol. 77, no. 3, pp. 160–163, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. U. Bhandari, R. Kanojia, and K. K. Pillai, “Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats,” Journal of Ethnopharmacology, vol. 97, no. 2, pp. 227–230, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. L. K. Han, X. J. Gong, S. Kawano, M. Saito, Y. Kimura, and H. Okuda, “Antiobesity actions of Zingiber officinale Roscoe,” Yakugaku Zasshi, vol. 125, no. 2, pp. 213–217, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. G. Kaur and S. K. Kulkarni, “Differential effect of polyherbal, antiobesity preparation, OB-200G in male and female mice and monosodium glutamate-treated rats,” Indian Journal of Experimental Biology, vol. 39, no. 6, pp. 551–557, 2001. View at Scopus
  60. G. Kaur and S. K. Kulkarni, “Investigations on possible serotonergic involvement in effects of OB-200G (polyherbal preparation) on food intake in female mice,” European Journal of Nutrition, vol. 40, no. 3, pp. 127–133, 2001. View at Publisher · View at Google Scholar · View at Scopus
  61. B. Fuhrman, M. Rosenblat, T. Hayek, R. Coleman, and M. Aviram, “Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice,” Journal of Nutrition, vol. 130, no. 5, pp. 1124–1131, 2000. View at Scopus
  62. G. Kaur and S. K. Kulkarni, “Antiobesity effect of a polyherbal formulation, OB-200G in female rats fed on cafeteria and atherogenic diets,” Indian Journal of Pharmacology, vol. 32, no. 5, pp. 294–299, 2000. View at Scopus
  63. U. Bhandari, J. N. Sharma, and R. Zafar, “The protective action of ethanolic ginger (Zingiber officinale) extract in cholesterol fed rabbits,” Journal of Ethnopharmacology, vol. 61, no. 2, pp. 167–171, 1998. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Tanabe, Y. D. Chen, K. Saito, and Y. Kano, “Cholesterol biosynthesis inhibitory component from Zingiber officinale Roscoe,” Chemical and Pharmaceutical Bulletin, vol. 41, no. 4, pp. 710–713, 1993. View at Scopus
  65. K. R. Shanmugam, K. Mallikarjuna, N. Kesireddy, and K. Sathyavelu Reddy, “Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin-induced diabetic rats,” Food and Chemical Toxicology, vol. 49, no. 4, pp. 893–897, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Pollreisz and U. Schmidt-Erfurth, “Diabetic cataract-pathogenesis, epidemiology and treatment,” Journal of Ophthalmology, vol. 2010, Article ID 608751, 8 pages, 2010. View at Publisher · View at Google Scholar
  67. A. Kato, Y. Higuchi, H. Goto et al., “Inhibitory effects of Zingiber officinale roscoe derived components on aldose reductase activity in vitro and in vivo,” Journal of Agricultural and Food Chemistry, vol. 54, no. 18, pp. 6640–6644, 2006. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Saraswat, P. Y. Reddy, P. Muthenna, and G. B. Reddy, “Prevention of non-enzymic glycation of proteins by dietary agents: prospects for alleviating diabetic complications,” British Journal of Nutrition, vol. 101, no. 11, pp. 1714–1721, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. M. Saraswat, P. Suryanarayana, P. Y. Reddy, M. A. Patil, N. Balakrishna, and G. B. Reddy, “Antiglycating potential of Zingiber officinalis and delay of diabetic cataract in rats,” Molecular Vision, vol. 16, pp. 1525–1537, 2010. View at Scopus
  70. W. Wang, C. Y. Li, X. D. Wen, P. Li, and L. W. Qi, “Simultaneous determination of 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol in rat plasma by liquid chromatography-mass spectrometry: application to pharmacokinetics,” Journal of Chromatography B, vol. 877, no. 8-9, pp. 671–679, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. T. Nakazawa and K. Ohsawa, “Metabolism of [6]-gingerol in rats,” Life Sciences, vol. 70, no. 18, pp. 2165–2175, 2002. View at Publisher · View at Google Scholar · View at Scopus
  72. E. Pfeiffer, F. F. Heuschmid, S. Kranz, and M. Metzler, “Microsomal hydroxylation and glucuronidation of [6]-gingerol,” Journal of Agricultural and Food Chemistry, vol. 54, no. 23, pp. 8769–8774, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. A. Asami, T. Shimada, Y. Mizuhara et al., “Pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe (Part I),” Journal of Natural Medicines, vol. 64, no. 3, pp. 281–287, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Z. Jiang, N. S. Wang, and S. Q. Mi, “Plasma pharmacokinetics and tissue distribution of [6]-gingerol in rats,” Biopharmaceutics and Drug Disposition, vol. 29, no. 9, pp. 529–537, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. S. M. Zick, Z. Djuric, M. T. Ruffin et al., “Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthyhuman subjects,” Cancer Epidemiology Biomarkers and Prevention, vol. 17, no. 8, pp. 1930–1936, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. Y. Yu, S. Zick, X. Li, P. Zou, B. Wright, and D. Sun, “Examination of the pharmacokinetics of active ingredients of ginger in humans,” BMC Biology, vol. 13, no. 3, pp. 417–426, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. D. Tiran, “Nausea and vomiting in pregnancy: safety and efficacy of self-administered complementary therapies,” Complementary Therapies in Nursing and Midwifery, vol. 8, no. 4, pp. 191–196, 2002. View at Publisher · View at Google Scholar · View at Scopus
  78. Evira Warning label to be added on food supplements containing ginger as well as on ginger tea, and corresponding drink powders, 2012, http://www.evira.fi/portal/en/food/manufacture_and_sales/labelling/warning_labelling_and_instructions_for_use/warning_label_to_be_added_on_food_supplements_containing_ginger_as_well_as_on_ginger_tea__and_corresponding_drink_powders.
  79. F. Borrelli, R. Capasso, G. Aviello, M. H. Pittler, and A. A. Izzo, “Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting,” Obstetrics and Gynecology, vol. 105, no. 4, pp. 849–856, 2005. View at Publisher · View at Google Scholar · View at Scopus
  80. G. Portnoi, L. A. Chng, L. Karimi-Tabesh, G. Koren, M. P. Tan, and A. Einarson, “Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy,” American Journal of Obstetrics and Gynecology, vol. 189, no. 5, pp. 1374–1377, 2003. View at Publisher · View at Google Scholar · View at Scopus
  81. M. S. Weidner and K. Sigwart, “Investigation of the teratogenic potential of a Zingiber officinale extract in the rat,” Reproductive Toxicology, vol. 15, no. 1, pp. 75–80, 2001. View at Publisher · View at Google Scholar · View at Scopus
  82. M. A. Shalaby and A. R. Hamowieh, “Safety and efficacy of Zingiber officinale roots on fertility of male diabetic rats,” Food and Chemical Toxicology, vol. 48, no. 10, pp. 2920–2924, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. M. Suekawa, A. Ishige, and K. Yuasa, “Pharmacological studies on ginger. I. Pharmacological actions of pungent constituents, (6)-gingerol and (6)-shogaol,” Journal of Pharmacobio-Dynamics, vol. 7, no. 11, pp. 836–848, 1984. View at Scopus
  84. X. Rong, G. Peng, T. Suzuki, Q. Yang, J. Yamahara, and Y. Li, “A 35-day gavage safety assessment of ginger in rats,” Regulatory Toxicology and Pharmacology, vol. 54, no. 2, pp. 118–123, 2009. View at Publisher · View at Google Scholar · View at Scopus