Advertisement

Gingerol and Its Role in Chronic Diseases

  • Yasmin Anum Mohd YusofEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 929)

Abstract

Since antiquity, ginger or Zingiber officinale, has been used by humans for medicinal purposes and as spice condiments to enhance flavor in cooking. Ginger contains many phenolic compounds such as gingerol, shogaol and paradol that exhibit antioxidant, anti-tumor and anti-inflammatory properties. The role of ginger and its constituents in ameliorating diseases has been the focus of study in the past two decades by many researchers who provide strong scientific evidence of its health benefit. This review discusses research findings and works devoted to gingerols, the major pungent constituent of ginger, in modulating and targeting signaling pathways with subsequent changes that ameliorate, reverse or prevent chronic diseases in human studies and animal models. The physical, chemical and biological properties of gingerols are also described. The use of ginger and especially gingerols as medicinal food derivative appears to be safe in treating or preventing chronic diseases which will benefit the common population, clinicians, patients, researchers, students and industrialists.

Keywords

Gingerol Signaling pathways Chronic diseases Physicochemical Biological properties 

References

  1. 1.
    Abdul Sani NF, Belani LK, Chong PS et al (2014) Effect of the Combination of Gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic sprague-dawley rats. Bio Med Res Int. doi: 10.1155/2014/160695 Google Scholar
  2. 2.
    Abdullah S, Abidin SAZ, Murad NA, Makpol S, Wan Ngah WZ, Mohd Yusof YA (2010) Ginger extract (Zingiber officinale) triggers apoptosis and G0/G1 cells arrest in HCT 116 and HT 29 colon cancer cell lines. Afr J Biochem Res 4:134–142Google Scholar
  3. 3.
    Aggarwal BB, Shishodia S (2006) Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol 71:1397–1421PubMedCrossRefGoogle Scholar
  4. 4.
    Ahui ML, Champy P, Ramadan A et al (2008) Ginger prevents Th2-mediated immune responses in a mouse model of airway inflammation. Int Immunopharmacol 8(12):1626–1632PubMedCrossRefGoogle Scholar
  5. 5.
    Akimoto M, Iizuka M, Kanematsu R et al (2015) Anticancer effect of ginger extract against pancreatic cancer cells mainly through reactive oxygen species-mediated autotic cell death. PLoS ONE 10(5):e0126605. doi: 10.1371/journal.pone.0126605 PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Aktan F, Henness S, Tran VH et al (2006) Gingerol metabolite and a synthetic analogue capsarol inhibit macrophage NF-kappa B-mediated iNOS gene expression and enzyme activity. Planta Med 72:27–734CrossRefGoogle Scholar
  7. 7.
    Al-Amin ZM, Thomson M, Al-Qattan KK et al (2006) Antidiabetic and hypolipidemic properties of ginger in streptozotocin induced diabetic rats. Br J Nutr 96:660–666PubMedCrossRefGoogle Scholar
  8. 8.
    Ali BH, Blunden G, Tanira MO et al (2008) Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol 46(2):409–420PubMedCrossRefGoogle Scholar
  9. 9.
    Alizadeh-Navaei R, Roozbeh F, Saravi M et al (2008) Investigation of the effect of ginger on the lipid levels. A double blind controlled clinical trial. Saudi Med J 29:1280–1284PubMedGoogle Scholar
  10. 10.
    Angel P, Karin M (1991) The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1072:129–157PubMedGoogle Scholar
  11. 11.
    Behrens J (2005) The role of the Wnt signalling pathway in colorectal tumorigenesis. Biochem Soc Trans 33:672–675PubMedCrossRefGoogle Scholar
  12. 12.
    Bharti AC, Aggarwal BB (2002) Nuclear factor-kappaB and cancer: its role in prevention and therapy. Biochem Pharmacol 64(5–6):883–888PubMedCrossRefGoogle Scholar
  13. 13.
    Bhattarai S, Tran VH, Duke CC (2007) Stability of [6]-gingerol and [6]-shogaol in simulated gastric and intestinal fluids. J Pharmaceut Biomed Anal 45:648–653CrossRefGoogle Scholar
  14. 14.
    Bode AM (2004) Cancer prevention by food factors through targeting signal transduction pathways. Nutr 20(1):80–94. doi: 10.1016/j.nut.2003.09 CrossRefGoogle Scholar
  15. 15.
    Bode AM, Dong Z (2004) Ginger. In: Packer L, Ong CN, Halliwell B (eds) Herbal and traditional medicine: molecular aspects of health. Marcel Dekker, New York, pp 131–156Google Scholar
  16. 16.
    Bode AM, Dong Z (2008) Modulation of cell signal transduction by tea and ginger. In: Dong Z, Surh YJ (ed) Dietary modulation of cell signaling pathways. CRC Press/Taylor & Francis, Boca Raton (FL), pp 45–74Google Scholar
  17. 17.
    Bode AM, Dong Z (2011) The amazing and mighty ginger. In: Benzie IFF, Wachtel-Galor S (ed) Herbal medicine: biomolecular and clinical aspects, 2nd edn. CRC Press/Taylor & Francis, Boca Raton (FL), pp 129–154Google Scholar
  18. 18.
    Bode AM, Ma WY, Surh YJ et al (2001) Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by [6]-gingerol. Cancer Res 61:850–853PubMedGoogle Scholar
  19. 19.
    Borrelli F, Capasso R, Aviello G et al (2005) Effectiveness and safety of ginger in the treatment of pregnancy induced Nausea and vomiting. Database of abstracts of reviews of effects (DARE): quality assessed reviews [Internet]. Centre for Reviews and Dissemination (UK), York (UK)Google Scholar
  20. 20.
    Butt MS, Sultan MT (2011) Ginger and its health claims: molecular aspects. Crit Rev Food Sci Nutr 51:383–393PubMedCrossRefGoogle Scholar
  21. 21.
    Cardone MH, Roy N, Stennicke HR et al (1998) Regulation of cell death protease caspase-9 by phosphorylation. Science 282:1318–1321PubMedCrossRefGoogle Scholar
  22. 22.
    Chakraborty D, Mukherjee A, Sikdar S et al (2012) [6]-gingerol isolated from ginger attenuates sodium arsenite induced oxidative stress and plays a corrective role in improving insulin signaling in mice. Toxicol Lett 210:34–43PubMedCrossRefGoogle Scholar
  23. 23.
    Chang F, Lee JT, Navolanic PM et al (2003) Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia 17(3):590–596PubMedCrossRefGoogle Scholar
  24. 24.
    Chen Z, Gibson TB, Robinson F et al (2001) MAP kinases. Chem Rev 101:2449–2476PubMedCrossRefGoogle Scholar
  25. 25.
    Citronberg J, Bostick R, Ahern T et al (2013) Effects of ginger supplementation on cell cycle biomarkers in the normal-appearing colonic mucosa of patients at increased risk for colorectal cancer: results from a pilot, randomized, controlled trial. Cancer Prev Res 6:271–281CrossRefGoogle Scholar
  26. 26.
    Clarke RB (2003) p27KIP1 phosphorylation by PKB/Akt leads to poor breast cancer prognosis. Breast Cancer Res 5(3):162–163PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Denniff P, Macleod I, Whiting DA (1980) Studies in the biosynthesis of [6]-gingerol, pungent principle of ginger (Zingiber officinale). J Chem Soc Perkin Trans 1:2637–2644CrossRefGoogle Scholar
  28. 28.
    Diehl JA (2002) Cycling to cancer with cyclin D1. Cancer Biol Ther 1(3):226–231PubMedCrossRefGoogle Scholar
  29. 29.
    Ding GH, Naora K, Hayashibara M et al (1991) Pharmacokinetics of [6]-gingerol after intravenous administration in rats. Chem Phar Bull (Tokyo) 39:1612–1614CrossRefGoogle Scholar
  30. 30.
    Dong Z, Birrer MJ, Watts RG et al (1994) Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells. Proc Natl Acad Sci U S A 91:609–613PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Dorai T, Aggarwal BB (2004) Role of chemopreventive agents in cancer therapy. Cancer Lett 215:129–140PubMedCrossRefGoogle Scholar
  32. 32.
    Dugasani S, Pichika MR, Nadarajah VD et al (2010) Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10] gingerol and [6]-shogaol. J Ethnopharmacol 127:515–520PubMedCrossRefGoogle Scholar
  33. 33.
    Ernst E, Pittler MH (2000) Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. Br J Anaesth 84(3):367–371PubMedCrossRefGoogle Scholar
  34. 34.
    Flynn DL, Rafferty MF, Boctor AM (1968) Inhibition of human neutrophil 5-lipoxygenase activity by gingerdione, shogaol, capsaicin and related pungent compounds. Prostaglandins Leukot Med 24:195–198CrossRefGoogle Scholar
  35. 35.
    Fresno-Vara JA, Casado E, Castro J et al (2004) PI3K/Akt signaling pathway and cancer. Cancer Treatment Rev 30:193–204CrossRefGoogle Scholar
  36. 36.
    Fulda S, Debatin KM (2006) Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25(34):4798–4811PubMedCrossRefGoogle Scholar
  37. 37.
    Giles RH, van Es JH, Clevers H (2003) Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 1653:1–24PubMedGoogle Scholar
  38. 38.
    Guertin DA, Sabatini DM (2007) Defining the role of mTOR in cancer. Cancer Cell 12:9–22PubMedCrossRefGoogle Scholar
  39. 39.
    Gundala SR, Mukkavilli R, Yang C et al (2014) Enterohepatic recirculation of bioactive ginger phytochemicals is associated with enhanced tumor growth-inhibitory activity of ginger extract. Carcinogenesis 35(6):1320–1329. doi: 10.1093/carcin/bgu011 Google Scholar
  40. 40.
    Gunning WT, Kramer PM, Steele VE et al (2002) Chemoprevetion by lipoxygenase and leukotriene pathway inhibitors of vinyl carbamate-induced lung tumours in mice. Cancer Res 62:4199–4201PubMedGoogle Scholar
  41. 41.
    Habib SH, Makpol S, Abdul Hamid NA et al (2008) Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats. Clinics (Sao Paulo) 63(6):807–813CrossRefGoogle Scholar
  42. 42.
    Harliyansyah H, Murad NA, Wan Ngah WZ et al (2007) Antiproliferative, antioxidant and apoptosis effects of Zingiber officinale and 6-gingerol on HepG2 cells. Asian J Biochem 2(6):421–426CrossRefGoogle Scholar
  43. 43.
    Hiserodt RD, Franzblau SG, Rosen RT (1998) Isolation of 6-, 8-, and 10-gingerol from ginger rhizome by HPLC and preliminary evaluation of inhibition of Mycobacterium avium and Mycobacterium tuberculosis. Agric Food Chem 46:2504–2508CrossRefGoogle Scholar
  44. 44.
    Huang HC, Chiu SH, Chang TM (2011) Inhibitory effect of [6]-gingerol on melanogenesis in B16F10 melanoma cells and a possible mechanism of action. Biosci Biotechnol Biochem 75(6):1067–1072PubMedCrossRefGoogle Scholar
  45. 45.
    Huang HC, Chou YC, Wu CY et al (2013) [8]-gingerol inhibits melanogenesis in murine melanoma cells through down-regulation of the MAPK and PKA signal pathways. Biochem Biophys Res Commun 438:375–381PubMedCrossRefGoogle Scholar
  46. 46.
    Hung JY, Hsu YL, Li CT et al (2009) 6-Shogaol, an active constituent of dietary ginger, induces autophagy by inhibiting the AKT/mTOR pathway in human non-small cell lung cancer A549 cells. J Agric Food Chem 57:9809–9816PubMedCrossRefGoogle Scholar
  47. 47.
    IARC monographs on the evaluation of carcinogenic risks to humans (1994) Lyon, France: international agency for research on cancer; IARC working group on the evaluation of carcinogenic risks to humans, schistomsomes, liver flukes and Helicobacter pylori. Infect Helicobacter pylori 61:177–201Google Scholar
  48. 48.
    Ippoushi K, Azuma K, Ito H et al (2003) [6]-gingerol inhibits nitric oxide synthesis in activated J774.1 mouse macrophages and prevents peroxynitrite-induced oxidation and nitration reactions. Life Sci 73:3427–3437PubMedCrossRefGoogle Scholar
  49. 49.
    Ishiguro K, Ando T, Maeda O et al (2007) Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms. Biochem Biophys Res Commun 362(1):218–223PubMedCrossRefGoogle Scholar
  50. 50.
    Issa AY, Volate SR, Wargovich MJ (2006) The role of phytochemicals in inhibition of cancer and inflammation: new directions and perspectives. J Food Compost Anal 19:405–419CrossRefGoogle Scholar
  51. 51.
    Jemal A, Bray F, Center M et al (2011) Global cancer statistics. CA: Cancer J Clin 61: 69–90Google Scholar
  52. 52.
    Jeong CH, Bode AM, Pugliese A et al (2009) [6]-gingerol suppresses colon cancer growth by targeting Leukotriene A4 Hydrolase. Cancer Res 69:5584–5591PubMedCrossRefGoogle Scholar
  53. 53.
    Jiang H, Solyom AM, Timmermann BN et al (2005) Characterization of gingerol-related compounds in ginger rhizome (Zingiber officinale Rosc.) by high-performance liquid chromatography/ electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 19(20):2957–2964PubMedCrossRefGoogle Scholar
  54. 54.
    Jiang Y, Turgeon DK, Wright BD et al (2013) Effect of ginger root on cyclooxygenase-1 and 15-hydroxyprostaglandin dehydrogenase expression in colonic mucosa of humans at normal and increased risk for colorectal cancer. Europ J Cancer Prevent 22(5):455–460CrossRefGoogle Scholar
  55. 55.
    Jolad SD, Lantz RC, Solyon AM et al (2004) Fresh organically grown ginger (Zingiber officinale): composition and effects on LPS-induced PGE2 production. Phytochem 65:1937–1954CrossRefGoogle Scholar
  56. 56.
    Jolad SD, Lantz RC, Chen GJ et al (2005) Commercially processed dry ginger (Zingiber officinale): composition and effects on LPS-stimulated PGE2 production. Phytochem 66(13):1614–1635CrossRefGoogle Scholar
  57. 57.
    Joo JH, Hong SS, Cho YR et al (2015) [10]-gingerol inhibits proliferation and invasion of MDA-MB-231 breast cancer cells through suppression of Akt and p38MAPK activity. Oncol Reports. doi: 10.3892/or.2015.4405 Google Scholar
  58. 58.
    Kamato D, Rezaei HB, Getachew R et al (2013) (S)-[6]-Gingerol inhibits TGF-β-stimulated biglycan synthesis but not glycosaminoglycan hyperelongation in human vascular smooth muscle cells. J Pharm Pharmacol 65:1026–1036PubMedCrossRefGoogle Scholar
  59. 59.
    Katiyar SK, Agarwal R, Mukhtar H (1996) Inhibition of tumor promotion in SENCAR mouse skin by ethanol extract of Zingiber officinalerhizome. Cancer Res 56(5):1023–1030PubMedGoogle Scholar
  60. 60.
    Kim EC, Min JK, Kim TY et al (2005) [6]-gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo. Biochem Biophys Res Commun 335(2):300–308PubMedCrossRefGoogle Scholar
  61. 61.
    Kim JK, Kim Y, Na KM et al (2007) [6]-Gingerol prevents UVB induced ROS production and COX-2 expression in vitro and in vivo. Free Rad Res 41:603–614CrossRefGoogle Scholar
  62. 62.
    Kim SO, Kim MR (2013) [6]-gingerol prevents disassembly of cell junctions and activities of MMPs in invasive human pancreas cancer cells through ERK/NF-κB/snail signal transduction pathway. Evid Based Complement Alternat Med 2013:761852. doi: 10.1155/2013/761852 PubMedPubMedCentralGoogle Scholar
  63. 63.
    Kim SO, Chun KS, Kundu JK et al (2004) Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF-kB and p38 MAPK in mouse skin. BioFactors 21:27–31PubMedCrossRefGoogle Scholar
  64. 64.
    Kim SO, Kundu JK, Shin YK et al (2005) [6]-gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-kappa B in phorbol ester-stimulated mouse skin. Oncogene 24(15):2558–2567PubMedCrossRefGoogle Scholar
  65. 65.
    Kiuchi F, Shibuya M, Sankawa U (1982) Inhibitors of prostaglandin biosynthesis from ginger. Chem Pharm Bull (Tokyo) 30:754–757CrossRefGoogle Scholar
  66. 66.
    Kobayashi M, Ishida Y, Shoji N et al (1988) Cardiotonic action of [8]-gingerol, an activator of the Ca2+-pumping adenosine triphosphatase of sarcoplasmic reticulum, in guinea pig atrial muscle. J Pharmacol Exp Ther 246:667–673PubMedGoogle Scholar
  67. 67.
    Koo KL, Ammit AJ, Tran VH et al (2001) Gingerols and related analogues inhibit arachidonic acid-induced human platelet serotonin release and aggregation. Thromb Res 103(5):387–397PubMedCrossRefGoogle Scholar
  68. 68.
    Kumar NV, Srinivas P, Bettadaiah BK (2012) New scalable and eco-friendly synthesis of gingerols. Tetrahedron Lett 53:2993–2995CrossRefGoogle Scholar
  69. 69.
    Lantz RC, Chen GJ, Sarihan M et al (2007) The effect of extracts from ginger rhizome on inflammatory mediator production. Phytomed 14:123–128CrossRefGoogle Scholar
  70. 70.
    Lee DH, Kim DW, Jung CH et al (2014) Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells. Toxicol Appl Pharmacol 279(3):253–265. doi: 10.1016/j.taap.2014.06.030 Google Scholar
  71. 71.
    Lee E, Surh YJ (1998) Induction of apoptosis in HL-60 cells by pungent vanilloids, [6]-gingerol and [6] paradol. Cancer Lett 134:163–168PubMedCrossRefGoogle Scholar
  72. 72.
    Lee HS, Seo EY, Kang NE, Kim WK (2008) [6]-Gingerol inhibits metastasis of MDS-MB-231 human breast cancer cells. J Nutr Biochem 19:313–319PubMedCrossRefGoogle Scholar
  73. 73.
    Lee SH, Cekanova M, Baek SJ (2008) Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells. Mol Carcinog 47(3):197–208PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Lee C, Park GH, Kim CY et al (2011) [6]-gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system. Food ChemToxicol 49:1261–1269CrossRefGoogle Scholar
  75. 75.
    Lin CC, Tsay GJ (2012) 6-gingerol inhibits growth of colon cancer cell LoVo via induction of G2/M arrest. Evid Based Complement Alternat Med. doi: 10.1155/2012/326096 Google Scholar
  76. 76.
    Ma S, Zhang S, Duan W et al (2009) An enantioselective synthesis of (+)-(S)-[n]-gingerols via the l-proline-catalyzed aldol reaction. Bioorganic Medic Chem Lett 19:3909–3911CrossRefGoogle Scholar
  77. 77.
    Maeda S, Omata M (2008) Inflammation and cancer: role of nuclear factor-kappa B activation. Cancer Sci 99:836–842PubMedCrossRefGoogle Scholar
  78. 78.
    Mahady GB, Pendland SL, Yun GS et al (2003) Ginger (Zingiber officinale Roscoe) and the gingerols inhibit the growth of Cag A+ strains of helicobacter pylori. Anticancer Res 23:3699–3702PubMedPubMedCentralGoogle Scholar
  79. 79.
    Maier LS, Schwan C, Schillinger W et al (2000) Gingerol, isoproterenol and ouabain normalize impaired post-rest behavior but not force-frequency relation in failing human myocardium. Cardiovasc Res 45:913–924PubMedCrossRefGoogle Scholar
  80. 80.
    Moran A, Ortega P, de Juan C et al (2010) Differential colorectal carcinogenesis: molecular basis and clinical relevance. World J Gastrointest Oncol 2:151–158. doi: 10.4251/wjgo.v2.i3.151 PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Nakazawa T, Ohsawa K (2002) Metabolism of [6]-gingerol in rats. Life Sci 70:2165–2175PubMedCrossRefGoogle Scholar
  82. 82.
    Neergheen VS, Bahorun T, Taylor EW et al (2010) Targeting specific cell signaling transduction pathways by dietary and medicinal phytochemicals in cancer chemoprevention. Toxicol 278:229–241CrossRefGoogle Scholar
  83. 83.
    Nigam N, Bhui K, Prasad S et al (2009) [6]-gingerol induces reactive oxygen species regulated mitochondrial cell death pathway in human epidermoid carcinoma A431 cells. Chem Biol Interact 181:77–84PubMedCrossRefGoogle Scholar
  84. 84.
    Nigam N, George J, Srivastava S et al (2010) Induction of apoptosis by [6]-gingerol associated with the modulation of p53 and involvement of mitochondrial signaling pathway in B[a]P-induced mouse skin tumorigenesis. Cancer Chemother Pharmacol 65:687–696PubMedCrossRefGoogle Scholar
  85. 85.
    Nurtjahja-Tjendraputra E, Ammit AJ, Roufogalis BD et al (2003) Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger. Thromb Res 111(4–5):259–265PubMedCrossRefGoogle Scholar
  86. 86.
    Ojewole JAO (2006) Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats. Phytother Res 20:764–772PubMedCrossRefGoogle Scholar
  87. 87.
    Ozes ON, Mayo LD, Gustin JA et al (1999) NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 401(6748):82–85PubMedCrossRefGoogle Scholar
  88. 88.
    Pana MH, Ho CT (2008) Chemopreventive effects of natural dietary compounds on cancer Development. Chem Soc Rev 37:2558–2574CrossRefGoogle Scholar
  89. 89.
    Park EJ, Pezzuto JM (2011) Botanicals in cancer chemoprevention. Cancer Metastasis Rev 21:231–255CrossRefGoogle Scholar
  90. 90.
    Park KK, Chun KS, Lee JM et al (1998) Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Lett 129(2):139–144PubMedCrossRefGoogle Scholar
  91. 91.
    Park M, Bae J, Lee DS (2008) Antibacterial activity of [10]-gingerol and [12]-gingerol isolated from ginger rhizome against periodontal bacteria. Phytother Res 22:1446–1449PubMedCrossRefGoogle Scholar
  92. 92.
    Park SA, Park IH, Cho JS et al (2012) Effect of [6]-gingerol on myofibroblast differentiation in transforming growth factor beta 1-induced nasal polyp-derived fibroblasts. Am J Rhinol Allergy 26(2):97–103PubMedCrossRefGoogle Scholar
  93. 93.
    ParkYJ; Wen J, Bang S et al (2006) [6]-gingerol induces cell cycle arrest and cell death of mutant p 53-expressing pancreatic cancer cells. Yonsei Med J 47(5): 688–697Google Scholar
  94. 94.
    Poltronieri J, Becceneri AB, Fuzer AM et al (2014) [6]-gingerol as a cancer chemopreventive agent: a review of its activity on different steps of the metastatic process. Mini Rev Med Chem 14(4):313–321PubMedCrossRefGoogle Scholar
  95. 95.
    Prasad S, Tyagi AK (2015) Ginger and its constituents: role in prevention and treatment of gastrointestinal cancer. Gastroenterol Res Practice. doi: 10.1155/2015/142979 Google Scholar
  96. 96.
    Prescott SM, Fitzpatrick FA (2000) Cyclooxygenase-2 and carcinogenesis. Biochim Biophys Acta 1470:M69–M67PubMedGoogle Scholar
  97. 97.
    Radhakrishnan EK, Bava SV, Narayanan SS et al (2014) [6]-gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling. PLoS ONE, 26:9(8):e104401. doi: 10.1371/journal.pone.0104401 Google Scholar
  98. 98.
    Ramirez-Ahumada MC, Timmermann BN, Gang DR (2006) Biosynthesis of curcuminoids and gingerols in turmeric (Curcuma longa) and ginger (Zingiber officinale): identification of curcuminoid synthase and hydroxycinnamoyl-CoA thioesterases. Phytochem 67:2017–2029CrossRefGoogle Scholar
  99. 99.
    Reed J (2001) Apoptosis-regulating proteins as targets for drug discovery. Trends Mol Med 7:314–319PubMedCrossRefGoogle Scholar
  100. 100.
    Rhode J, Fogoros S, Zick S et al (2007) Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells. BMC Complement Alternat Med 7:44CrossRefGoogle Scholar
  101. 101.
    Riaz H, Begum A, Raza SA et al (2015) Antimicrobial property and phytochemical study of ginger found in local area of Punjab, Pakistan. Internat Curr Pharmaceut J 4(7):405–409CrossRefGoogle Scholar
  102. 102.
    Ryu MJ, Chung HS (2015) [10]-gingerol induces mitochondrial apoptosis through activation of MAPK pathway in HCT116 human colon cancer cells. Vitro Cell Dev Biol Anim 51(1):92–101. doi: 10.1007/s11626-014-9806-6 CrossRefGoogle Scholar
  103. 103.
    Scheiman JM, Cutler AF (1999) Helicobacter pylori and gastric cancer. Am J Med 106:222–226PubMedCrossRefGoogle Scholar
  104. 104.
    Semwal RB, Semwal DK, Combrinck S et al (2015) Gingerols and shogaols: important nutraceutical principles from ginger. Phytochem 117:554–568CrossRefGoogle Scholar
  105. 105.
    Shukla Y, Singh M (2007) Cancer preventive properties of ginger: a brief review. Food Chem Toxicol 45(5):683–690PubMedCrossRefGoogle Scholar
  106. 106.
    Sporn MB, Dunlop NM, Newton DL et al (1976) Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc 35:1332–1338PubMedGoogle Scholar
  107. 107.
    Song G, Quyang G, Bao S (2005) The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 9(1):59–71PubMedCrossRefGoogle Scholar
  108. 108.
    Subbaramaiah K, Dannenberg AJ (2003) Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol Sci 24:96–102PubMedCrossRefGoogle Scholar
  109. 109.
    Surh YJ, Lee E, Lee JM (1998) Chemoprotective properties of some pungent ingredients present in red pepper and ginger. Mutat Res 402(1–2):259–267PubMedCrossRefGoogle Scholar
  110. 110.
    Surh YJ, Lee SS(1994) Enzymic reduction of gingerol, a major pungent principle of ginger, in the cell-free preparation of rat liver. Life Sci 54:PL321–PL326Google Scholar
  111. 111.
    Tahir AA, Abdul Sani NF, Morad NA et al (2015) Combined ginger extract and gelam honey modulate Ras/ERK and P13/AKT pathway genes in colon cancer HT29 cells, Nutr J 13:31Google Scholar
  112. 112.
    Talalay P (2001) The importance of using scientific principles in the development of medicinal agents from plants. Acad Med 76(3):238–247PubMedCrossRefGoogle Scholar
  113. 113.
    Tarapore RS, Siddiqui IA, Mukhtar H (2012) Modulation of Wnt/β-catenin signaling pathway by bioactive food components. Carcinogenesis 33(3):483–491. doi: 10.1093/carcin/bgr305 PubMedCrossRefGoogle Scholar
  114. 114.
    Townsend EA, Siviski ME, Zhang Y et al (2013) Effects of ginger and its constituents on airway smooth muscle relaxation and calcium regulation. Am J Respir Cell Mol Biol 48(2):157–163. doi: 10.1165/rcmb.2012-0231OC PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Vogelstein B, Kinzler KW (1992) p53 function and dysfunction. Cell 70(4):523–526PubMedCrossRefGoogle Scholar
  116. 116.
    Vutyavanich T, Kraisin T, Ruangsri R (2001) Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet Gynecol 97(4):577–582PubMedGoogle Scholar
  117. 117.
    Wang CC, Chen LG, Lee LT et al (2003) Effects of 6-gingerol, an antioxidant from ginger, on inducing apoptosis in human leukemic HL-60 cells. In Vivo 17:641–645PubMedGoogle Scholar
  118. 118.
    Wee LH, Morad NA, Aan GJ et al (2015) Mechanism of chemoprevention against colon cancer cells using combined Gelam honey and ginger extract via mTOR and Wnt/β-catenin pathways. Asian Pac J Cancer Prev 16:6549–6556Google Scholar
  119. 119.
    Wei QY, Ma JP, Cai YJ et al (2005) Cytotoxic and apoptotic activities of diarylheptanoids and gingerol-related compounds from the rhizome of Chinese ginger. J Ethnopharmacol 102:177–184PubMedCrossRefGoogle Scholar
  120. 120.
    Weng CJ, Wu CF, Huang HW et al (2010) Anti-invasion effects of 6-shogaol and 6-gingerol, two active components in ginger, on human hepatocarcinoma cells. Mol Nutr Food Res 54(11):1618–1627PubMedCrossRefGoogle Scholar
  121. 121.
    Weng CJ, Chou CP, Ho CT et al (2012) Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol. Mol Nutr Food Res 56(8):1304–1314PubMedCrossRefGoogle Scholar
  122. 122.
    Wohlmuth H, Leach DN, Smith MK et al (2005) Gingerol content of diploid and tetraploid clones of ginger (Zingiber officinale Roscoe). J Agric Food Chem 53:5772–5778PubMedCrossRefGoogle Scholar
  123. 123.
    Wu KK, Wang XJ, Cheng AS et al (2013) Dysregulation and crosstalk of cellular signaling pathways in colon carcinogenesis. Crit Rev Oncol/Hemato l86: 251–277Google Scholar
  124. 124.
    Yagihashi S, Miura Y, Yagasaki K (2008) Inhibitory effect of gingerol on the proliferation and invasion of hepatoma cells in culture. Cytotechnology 57:129–136PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Yang G, Wang S, Zhong L et al (2012) [6]-gingerol induces apoptosis through lysosomal-mitochondrial axis in human hepatoma G2 cells. Phytother Res 26(11):1667–1673PubMedCrossRefGoogle Scholar
  126. 126.
    Yang G, Zhong L, Jiang L et al (2010) Genotoxic effect of 6-gingerol on human hepatoma G2 cells. Chem Biol Interact 185(1):12–17PubMedCrossRefGoogle Scholar
  127. 127.
    Yoon JH, Baek SJ (2005) Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J 46(5):585–596. doi: 10.3349/ymj.2005.46.5.585 PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Yoshimi N, Wang A, Morishita Y et al (1992) Modifying effects of fungal and herb metabolites on azoxymethane-induced intestinal carcinogenesis in rats. Jpn J Cancer Res 83(12):1273–1278PubMedCrossRefGoogle Scholar
  129. 129.
    Yusof YAM, Ahmad N, Das S et al (2009) Chemopreventive efficacy of ginger (Zingiber officinale) in ethionine induced rat hepatocarcinogenesis. Afr J Tradit Complem Altern Med 6:87–93Google Scholar
  130. 130.
    Zhang S, Liu Q, Liu Y et al (2012) Zerumbone, a Southeast Asian ginger sesquiterpene, induced apoptosis of pancreatic carcinoma cells through p53 signaling pathway. Evid Based Complement Alternat Med. doi: 10.1155/2012/936030 Google Scholar
  131. 131.
    Zhang YX, Li JS, Chen LH et al (2012) Simultaneous determination of five gingerols in raw and processed ginger by HPLC. Chinese Pharm J 47:471–474Google Scholar
  132. 132.
    Zick SM, Djuric Z, Ruffin MT et al (2008) Pharmacokinetics of 6-, 8-, 10-gingerols and 6-shogaol and conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev 17(8):1930–1936. doi: 10.1158/1055-9965.EPI-07-2934 PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Zick SM, Turgeon DK, Ren J et al (2015) Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer. Mol Carcinog 54(9):908–915. doi: 10.1002/mc.22163 PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Biochemistry, Faculty of MedicineUniversiti Kebangsaan MalaysiaCherasMalaysia

Personalised recommendations