Gingerols and shogaols: Important nutraceutical principles from ginger

Phytochemistry

Volumn 117, Issue , 2015, Pages 554-568

  Semwal, Ruchi Badoni ^a   Semwal, Deepak Kumar ^a   Combrinck, Sandra ^a   Viljoen, Alvaro M ^a,b  

^a TSHWANE UNIVERSITY OF TECHNOLOGY   (South Africa)

^b KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

Author keywords

Anti inflammatory; Anticancer; Antidiabetic; Ginger; Gingerols; Nutraceutical; Shogaols; Zingiber officinale

Indexed keywords

ZINGIBER OFFICINALE;

ANTIALLERGIC AGENT; ANTIDIABETIC AGENT; ANTIINFECTIVE AGENT; ANTINEOPLASTIC AGENT; ANTIOBESITY AGENT; CATECHOL DERIVATIVE; FATTY ALCOHOL; GINGEROL; SHOGAOL;

ANIMAL; CHEMISTRY; DIETARY SUPPLEMENT; DISEASE MODEL; GINGER; HUMAN; MEDICINAL PLANT; METABOLISM;

ANIMALS; ANTI-ALLERGIC AGENTS; ANTI-INFECTIVE AGENTS; ANTI-OBESITY AGENTS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; CATECHOLS; DIETARY SUPPLEMENTS; DISEASE MODELS, ANIMAL; FATTY ALCOHOLS; GINGER; HUMANS; HYPOGLYCEMIC AGENTS; PLANTS, MEDICINAL;

EID: 84940467324     PISSN: 00319422     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.phytochem.2015.07.012     Document Type: Short Survey

References (174)

1. R. Aeschbach, J. Loliger, B.C. Scott, A. Murcia, J. Butler, B. Halliwell, and O.I. Aruoma Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxytyrosol Food Chem. Toxicol. 32 1994 31 36
2. S.I. Ahn, J.K. Lee, and H.S. Youn Inhibition of homodimerization of toll-like receptor 4 by 6-shogaol Mol. Cells 27 2009 211 215
3. N.M. Al-Daghri, M.S. Alokail, K.M. Alkharfy, A.K. Mohammed, S.H. Abd-Alrahman, S.M. Yakout, O.E. Amer, and S. Krishnaswamy Fenugreek extract as an inducer of cellular death via autophagy in human T lymphoma Jurkat cells BMC Complement. Altern. Med. 12 2012 202
4. S. Alqasoumi, H. Yusufoglu, A. Farraj, and A. Alam Effect of 6-shogaol and 6-gingerol on diclofenac sodium induced liver injury Int. J. Pharmacol. 7 2011 868 873
5. 2+-ATPase J. Pharmacol. Exp. Ther. 290 1999 227 234
6. M.S. Baliga, R. Haniadka, M.M. Pereira, J.J. D'Souza, P.L. Pallaty, H.P. Bhat, and S. Popuri Update on the chemopreventive effects of ginger and its phytochemicals Crit. Rev. Food Sci. Nutr. 51 2011 499 523
7. A. Barco, S. Benetti, P.G. Baraldi, M. Guarneri, G.P. Pollini, and D. Simoni 3,5-Disubstituted isoxazoles as a latent aldol moiety: application to the synthesis of (±)-[6]-gingerol J. Chem. Soc., Chem. Commun. 1981 599 600
8. T. Beg, Y.H. Siddique, G. Ara, J. Gupta, and M. Afzal Antigenotoxic effect of genistein and gingerol on genotoxicity induced by norethandrolone and oxandrolone in cultured human lymphocytes Int. J. Pharmacol. 4 2008 177 183
9. S. Bhattarai, V.H. Tran, and C.C. Duke Stability of [6]-gingerol and [6]-shogaol in simulated gastric and intestinal fluids J. Pharm. Biomed. Anal. 45 2007 648 653
10. A.M. Bode, W.Y. Ma, Y.J. Surh, and Z. Dong Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by [6]-gingerol Cancer Res. 61 2001 850 853
11. M.S. Butt, and M.T. Sultan Ginger and its health claims: molecular aspects Crit. Rev. Food Sci. Nutr. 51 2011 383 393
12. D. Chakraborty, K. Bishayee, S. Ghosh, R. Biswas, S. Kumar Mandal, and A.R. Khuda-Bukhsh [6]-Gingerol induces caspase 3 dependent apoptosis and autophagy in cancer cells: drug-DNA interaction and expression of certain signal genes in HeLa cells Eur. J. Pharmacol. 694 2012 20 29
13. 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 Toxicol. Lett. 210 2012 34 43
14. C.J. Chang, T.F. Tzeng, S.S. Liou, Y.S. Chang, and I.M. Liu Absence of genotoxic and mutagenic effects of Zingiber zerumbet (L.) Smith (Zingiberaceae) extract Evid. Based Complement. Alternat. Med. 2012 406296
15. K.L.N. Chari, D. Manasa, P. Srinivas, and H.B. Sowbhagya Enzyme-assisted extraction of bioactive compounds from ginger (Zingiber officinale Roscoe) Food Chem. 139 2013 509 514
16. 2+ mobilization in Madin-Darby canine kidney cells J. Nat. Prod. 71 2008 137 140
17. H. Chen, D.N. Soroka, J. Haider, K.F. Ferri-Lagneau, T. Leung, and S. Sang [10]-Gingerdiols as the major metabolites of [10]-gingerol in zebrafish embryos and in humans and their hematopoietic effects in zebrafish embryos J. Agric. Food Chem. 61 2013 5353 5360
18. E.M. Choi, and Y.H. Kim Effect of [6]-gingerol, a pungent ingredient of ginger, on osteoblast response to extracellular reducing sugar Food Sci. Biotechnol. 16 2007 807 811
19. I. Dehghani, A. Mostajeran, and G. Asghari In vitro and in vivo production of gingerols and zingiberene in ginger plant (Zingiber officinale Roscoe) Iran. J. Pharm. Sci. 7 2011 129 133
20. P. Denniff, and D.A. Whiting Biosynthesis of [6]-gingerol, pungent principle of Zingiber officinale J. Chem. Soc., Chem. Commun. 1976 711 712
21. P. Denniff, and D.A. Whiting Synthesis of (±)-[6]-gingerol (pungent principle of ginger) and relatives via directed aldol reactions J. Chem. Soc., Chem. Commun. 1976 712 713
22. P. Denniff, I. Macleod, and D.A. Whiting Studies in the biosynthesis of [6]-gingerol, pungent principle of ginger (Zingiber officinale) J. Chem. Soc. Perkin Trans. 1 1980 2637 2644
23. P. Denniff, I. Macleod, and D.A. Whiting Syntheses of the (±)-[n]-gingerols (pungent principles of ginger) and related compounds through regioselective aldol condensations: relative pungency assays J. Chem. Soc. Perkin Trans. 1 1981 82 87
24. G. Ding, K. Naora, M. Hayashibara, Y. Katagiri, Y. Kano, and K. Iwamoto Pharmacokinetics of [6]-gingerol after intravenous administration in rats Chem. Pharm. Bull. 39 1991 1612 1614
25. S. Dugasani, M.R. Pichika, V.D. Nadarajah, M.K. Balijepalli, S. Tandra, and J.N. Korlakunta Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol J. Ethnopharmacol. 127 2010 515 520
26. W.M. El-Bakly, M.L. Louka, A.M. El-Halawany, and M.F. Schaalan 6-gingerol ameliorated doxorubicin-induced cardiotoxicity: role of nuclear factor kappa B and protein glycation Cancer Chemother. Pharmacol. 70 2012 833 841
27. A.T.G. Elzebroek, and K. Wind Guide to Cultivated Plants 2008 CAB International Wallingford, Oxfordshire, UK pp. 276-279
28. D. Enders, H. Eichenauer, and R. Pieter Enantioselective synthesis of (-)-(R) and (+)-(S)-[6]-Gingerol - pungent principle of ginger Chem. Berichte 112 1979 3703 3714
29. S. Farhath, P.P. Vijaya, and M. Vimal Immunomodulatory activity of geranial, geranial acetate, gingerol, and eugenol essential oils: evidence for humoral and cell-mediated responses Avicenna J. Phytomed. 3 2013 224 230
30. S.A. Fleming, C.W. Dyer, and J. Eggington A convenient one-step gingerol synthesis Syn. Commun. 29 1999 1933 1939
31. F.F. Gan, A.A. Nagle, X. Ang, O.H. Ho, S.H. Tan, H. Yang, W.K. Chui, and E.H. Chew Shogaols at proapoptotic concentrations induce G 2/M arrest and aberrant mitotic cell death associated with tubulin aggregation Apoptosis 16 2011 856 867
32. M.L. Gauthier, J. Douat, P. Vachon, and F. Beaudry Characterization of [6]-gingerol metabolism in rat by liquid chromatography electrospray tandem mass spectrometry Biomed. Chromatogr. 25 2011 1150 1158
33. M.L. Gauthier, F. Beaudry, and P. Vachon Intrathecal [6]-gingerol administration alleviates peripherally induced neuropathic pain in male Sprague-Dawley rats Phytother. Res. 27 2013 1251 1254
34. B.P. Giovanni, M. Fabio, P.G. Piero, S. Daniele, B. Achille, and B. Simonetta Asymmetric synthesis of a β-ketol moiety via 3,5-disubstituted isoxazoles: application to (+)-(S)-[6]-gingerol J. Chem. Soc. Perkin Trans. 1 1982 2983 2987
35. C. Goto, S. Kasuya, K. Koga, H. Ohtoma, and N. Kagei Lethal efficacy of extract from Zingiber officinale (traditional Chinese medicine) or [6]-shogaol and [6]-gingerol in Anisakis larvae in vitro Parasitol. Res. 76 1990 653 656
36. B. Groblacher, V. Maier, O. Kunert, and F. Bucar Putative mycobacterial efflux inhibitors from the seeds of Aframomum melegueta J. Nat. Prod. 75 2012 1393 1399
37. J.H. Guh, F.N. Ko, T.T. Jong, and C.M. Teng Antiplatelet effect of gingerol isolated from Zingiber officinale J. Pharm. Pharmacol. 47 1995 329 332
38. F. Guo, and Y. Li Phenolic and amide constituents from Lycianthes marlipoensis China J. Chin. Mat. Med. 36 2011 2507 2510
39. S.K. Ha, E. Moon, M.S. Ju, D.H. Kim, J.H. Ryu, M.S. Oh, and S.Y. Kim 6-Shogaol, a ginger product, modulates neuroinflammation: a new approach to neuroprotection Neuropharmacology 63 2012 211 223
40. Y.Q. Han, Y. Hong, J.R. Gao, J. Gui, Y.Z. Wang, L.Z. Xia, and L.S. Zheng Processing technology of Zingiberis Rhizoma Praeparata based on UPLC fingerprints and quantitative determination of index components Chin. Trad. Herb. Drugs 44 2013 42 46
41. Y. Hata, L.R. Pancho, H. Nojima, and I. Kimura Endothelium-dependent potentiation of prostaglandin F(2α)-induced contractions by (±)-[6]-Gingerol is inhibited by cyclooxygenase-but not lipoxygenase-inhibitors in mouse mesenteric veins Biol. Pharm. Bull. 21 1998 792 794
42. X.-G. He, M.W. Bernart, L.-Z. Lian, and L.-Z. Lin High-performance liquid chromatography-electrospray mass spectrometric analysis of pungent constituents of ginger J. Chromatogr. A 796 1998 327 334
43. N. Hirao, J. Kawachi, and B. Yasui Synthesis of natural gingerol Chem. Pharm. Bull. 21 1973 2569 2571
44. H. Hiroshi, K. Yoshinobu, K. Nobuharu, H. Yasumasa, S. Takayuki, A. Ritsuo, I. Hideji, K. Fumiyuki, and S. Ushio Antihepatotoxic actions of gingerols and diarylheptanoids J. Ethnopharmacol. 14 1985 31 39
45. R.D. Hiserodt, S.G. Franzblau, and R.T. Rosen Isolation of 6-, 8-, and 10-gingerol from ginger rhizome by HPLC and preliminary evaluation of inhibition of Mycobacterium avium and Mycobacterium tuberculosis J. Agric. Food Chem. 46 1998 2504 2508
46. S.C. Ho, K.S. Chang, and C.C. Lin Anti-neuroinflammatory capacity of fresh ginger is attributed mainly to 10-gingerol Food Chem. 141 2013 3183 3191
47. X. Huang, and N. Peng 6-Gingerol function against fatigue Adv. Mater. Res. 340 2012 254 258
48. H.C. Huang, S.H. Chiu, and T.M. Chang Inhibitory effect of [6]-gingerol on melanogenesis in B16F10 melanoma cells and a possible mechanism of action Biosci. Biotechnol. Biochem. 75 2011 1067 1072
49. H.C. Huang, Y.C. Chou, C.Y. Wu, and T.M. Chang [8]-Gingerol inhibits melanogenesis in murine melanoma cells through down-regulation of the MAPK and PKA signal pathways Biochem. Biophys. Res. Commun. 438 2013 375 381
50. K. Ippoushi, K. Azuma, H. Ito, H. Horie, and H. Higashio [6]-Gingerol inhibits nitric oxide synthesis in activated J774.1 mouse macrophages and prevents peroxynitrite-induced oxidation and nitration reactions Life Sci. 73 2003 3427 3437
51. K. Ippoushi, H. Ito, H. Horie, and K. Azuma Mechanism of inhibition of 1 peroxynitrite-induced oxidation and nitration by [6]-gingerol Planta Med. 71 2005 563 566
52. Y. Isa, Y. Miyakawa, M. Yanagisawa, T. Goto, M.-S. Kang, T. Kawada, Y. Morimitsu, K. Kubota, and T. Tsuda 6-Shogaol and 6-gingerol, the pungent of ginger, inhibit TNF-α mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes Biochem. Biophys. Res. Commun. 373 2008 429 434
53. S.P. Ittiyavirah, and M. Paul In silico docking analysis of constituents of Zingiber officinale as antidepressant J. Pharmacogn. Phytother. 5 2013 101 105
54. Y. Iwasaki, A. Morita, T. Iwasawa, K. Kobata, Y. Sekiwa, Y. Morimitsu, K. Kubota, and T. Watanabe A nonpungent component of steamed ginger-[10]-shogaol-increases adrenaline secretion via the activation of TRPV1 Nutr. Neurosci. 9 2006 169 178
55. C.H. Jeong, A.M. Bode, A. Pugliese, Y.Y. Cho, H.G. Kim, J.H. Shim, Y.J. Jeon, H. Li, H. Jiang, and Z. Dong [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A 4 hydrolase Cancer Res. 69 2009 5584 5591
56. J.K. Jeong, M.H. Moon, Y.G. Park, J.H. Lee, Y.J. Lee, J.W. Seol, and S.Y. Park Gingerol-induced hypoxia-inducible factor 1 alpha inhibits human prion peptide-mediated neurotoxicity Phytother. Res. 27 2013 1185 1192
57. H. Jiang, A.M. Sólyom, B.N. Timmermann, and D.R. Gang 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 2005 2957 2964
58. S.Z. Jiang, N.S. Wang, and S.Q. Mi Plasma pharmacokinetics and tissue distribution of [6]-gingerol in rats Biopharm. Drug Dispos. 29 2008 529 537
59. S.Y. Joo, and Y.C. Lim Inhibitory effects of 6-gingerol on cytochrome P450 in human liver microsomes J. Korean Soc. Clin. Pharmacol. Ther. 19 2011 52 58
60. S.A. Ju, S.M. Park, Y.S. Lee, J.H. Bae, R. Yu, W.G. An, J.H. Suh, and B.S. Kim Administration of 6-gingerol greatly enhances the number of tumor-infiltrating lymphocytes in murine tumors Int. J. Cancer 130 2012 2618 2628
61. D. Kamato, H.B. Rezaei, R. Getachew, L. Thach, D. Guidone, N. Osman, B. Roufogalis, C.C. Duke, V.H. Tran, W. Zheng, and P.J. Little (S)-[6]-Gingerol inhibits TGF-β-stimulated biglycan synthesis but not glycosaminoglycan hyperelongation in human vascular smooth muscle cells J. Pharm. Pharmacol. 65 2013 1026 1036
62. A. Khaki, and F. Fathiazad Diabetic nephropathy - using herbals in diabetic nephropathy prevention and treatment - the role of ginger (Zingiber officinale) and onion (Allium cepa) in diabetics' nephropathy A. Bhattacharya, A Compendium of Essays on Alternative Therapy 2012 InTech Publisher Rijeka, Croatia 207 232
63. H.K. Kim, Y.A. Kim, S.W. Hwang, and B.S. Ko Quantitative analysis of 6-gingerol in the Zingiberis Rhizoma by processing methods Korean J. Pharmacogn. 33 2002 291 295
64. S.O. Kim, K.S. Chun, J.K. Kundu, and Y.J. Surh Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF-kappaB and p38 MAPK in mouse skin BioFactors 21 2004 27 31
65. E.C. Kim, J.K. Min, T.Y. Kim, S.J. Lee, H.O. Yang, S. Han, Y.M. Kim, and Y.G. Kwon [6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo Biochem. Biophys. Res. Commun. 335 2005 300 308
66. S.O. Kim, J.K. Kundu, Y.K. Shin, J.H. Park, M.H. Cho, T.Y. Kim, and Y.J. Surh [6]-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-κB in phorbol ester-stimulated mouse skin Oncogene 24 2005 2558 2567
67. J.K. Kim, Y. Kim, K.M. Na, Y.J. Surh, and T.Y. Kim [6]-Gingerol prevents UVB-induced ROS production and COX-2 expression in vitro and in vivo Free Rad. Res. 41 2007 603 614
68. J.S. Kim, S.I. Lee, H.W. Park, J.H. Yang, T.Y. Shin, Y.C. Kim, N.I. Baek, S.H. Kim, S.U. Choi, B.M. Kwon, K.H. Leem, M.Y. Jung, and D.K. Kim Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe Arch. Pharm. Res. 31 2008 415 418
69. J.H. Kim, J.H. Chang, J.H. Yoon, S.H. Kwon, J.H. Bae, and K.S. Kim [6]-Gingerol suppresses interleukin-1β-induced MUC5AC gene expression in human airway epithelial cells Am. J. Rhinol. Allergy 23 2009 385 391
70. I. Kimura, L.-R. Pancho, T. Shioiri, and M. Kimura Suppression of spontaneous calcium spikes and contraction in isolated portal veins of mice by gingerols and chemically related compounds Jpn. J. Pharmacol. 48 1988 257 262
71. 2+-pumping ATPase in skeletal and cardiac sarcoplasmic reticulum Biochim. Biophys. Acta - Biomembranes 903 1987 96 102
72. 2+-pumping adenosine triphosphatase of sarcoplasmic reticulum, in guinea pig atrial muscle J. Pharmacol. Exp. Ther. 246 1988 667 673
73. A. Kuhad, N. Tirkey, S. Pilkhwal, and K. Chopra 6-Gingerol prevents cisplatin-induced acute renal failure in rats BioFactors 26 2006 189 200
74. N.V. Kumar, P. Srinivas, and B.K. Bettadaiah New scalable and eco-friendly synthesis of gingerols Tetrahedron Lett. 53 2012 2993 2995
75. A. Lapworth, I.K. Pearson, and F.A. Royle The pungent principles of ginger. Part I: The chemical characters and decomposition products of thresh's "gingerol" J. Chem. Soc. 111 1917 777
76. T. Le Gall, J.P. Lellouche, and J.P. Beaucourt An organo-iron mediated chiral synthesis of (+)-(S)-[6]-gingerol Tetrahedron Lett. 30 1989 6521 6524
77. E. Lee, and Y.J. Surh Induction of apoptosis in HL-60 cells by pungent vanilloids, [6]-gingerol and [6]-paradol Cancer Lett. 134 1998 163 168
78. H.S. Lee, E.Y. Seo, N.E. Kang, and W.K. Kim [6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells J. Nutr. Biochem. 19 2008 313 319
79. S.H. Lee, M. Cekanova, and J.B. Seung Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells Mol. Carcinog. 47 2008 197 208
80. T.Y. Lee, K.C. Lee, S.Y. Chen, and H.H. Chang 6-Gingerol inhibits ROS and iNOS through the suppression of PKC-α and NF-κB pathways in lipopolysaccharide-stimulated mouse macrophages Biochem. Biophys. Res. Commun. 382 2009 134 139
81. C. Lee, G.H. Park, C.Y. Kim, and J.H. Jang [6]-Gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system Food Chem. Toxicol. 49 2011 1261 1269
82. S.W. Lee, J.H. Lim, M.S. Kim, J.H. Jeong, G.Y. Song, W.S. Lee, and M.C. Rho Phenolic compounds isolated from Zingiber officinale roots inhibit cell adhesion Food Chem. 128 2011 778 782
83. 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 Med. 78 2012 1549 1555
84. M. Li, P.Z. Chen, Q.X. Yue, J.Q. Li, R.A. Chu, W. Zhang, and H. Wang Pungent ginger components modulates human cytochrome P450 enzymes in vitro Acta Pharmacol. Sin. 34 2013 1237 1242
85. X.H. Li, K.C.Y. McGrath, V.H. Tran, Y.M. Li, S. Mandadi, C.C. Duke, A.K. Heather, and B.D. Roufogalis Identification of a calcium signalling pathway of S-[6]-gingerol in HuH-7 cells Evid. Based Complement. Alternat. Med. 2013 951758
86. X.H. Li, K.C.Y. McGrath, V.H. Tran, Y.-M. Li, C.C. Duke, B.D. Roufogalis, and A.K. Heather Attenuation of proinflammatory responses by S-[6]-Gingerol via inhibition of ROS/NF-Kappa B/COX2 activation in HuH7 cells Evid. Based Complement. Alternat. Med. 2013 146142
87. Y.R. Liao, Y.L. Leu, Y.Y. Chan, P.C. Kuo, and T.S. Wu Anti-platelet aggregation and vasorelaxing effects of the constituents of the rhizomes of Zingiber officinale Molecules 17 2012 8928 8937
88. C.B. Lin, C.C. Lin, and G.J. Tsay 6-Gingerol inhibits growth of colon cancer cell LoVo via induction of G2/M arrest Evid. Based Complement. Alternat. Med. 2012 326096
89. Q. Liu, J. Liu, H. Guo, S. Sun, S. Wang, Y. Zhang, S. Li, and Y. Qiao [6]-Gingerol: a novel AT1 antagonist for the treatment of cardiovascular disease Planta Med. 79 2013 322 326
90. J. Lu, S. Guan, X. Shen, W. Qian, G. Huang, X. Deng, and G. Xie Immunosuppressive activity of 8-gingerol on immune responses in mice Molecules 16 2011 2636 2645
91. L. Lv, H. Chen, D. Soroka, X. Chen, T. Leung, and S. Sang 6-Gingerdiols as the major metabolites of 6-gingerol in cancer cells and in mice and their cytotoxic effects on human cancer cells J. Agric. Food Chem. 60 2012 11372 11377
92. I. Macleod, and D.A. Whiting Stages in the biosynthesis of [6]-gingerol in Zingiber officinale J. Chem. Soc., Chem. Commun. 1979 1152 1153
93. G.B. Mahady, S.L. Pendland, G.S. Yun, Z.Z. Lu, and A. Stoia Ginger (Zingiber officinale Roscoe) and the gingerols inhibit the growth of Cag A+ strains of Helicobacter pylori Anticancer Res. 23 2003 3699 3702
94. L.S. Maier, C. Schwan, W. Schillinger, K. Minami, U. Schütt, and B. Pieske Gingerol, isoproterenol and ouabain normalize impaired post-rest behavior but not force-frequency relation in failing human myocardium Cardiovasc. Res. 45 2000 913 924
95. M. Martin, and P. Guibet Synthesis of the [8] gingerol enantiomers Chirality 3 1991 151 155
96. Y. Miao, Y. Sun, W. Wang, B. Du, S.-E. Xiao, Y. Hu, and Z. Hu 6-Gingerol inhibits hair shaft growth in cultured human hair follicles and modulates hair growth in mice PLoS One 8 2013 e57226
97. E. Morera, L. De Petrocellis, L. Morera, A.S. Moriello, M. Nalli, V. Di Marzo, and G. Ortar Synthesis and biological evaluation of [6]-gingerol analogues as transient receptor potential channel TRPV1 and TRPA1 modulators Bioorg. Med. Chem. Lett. 22 2012 1674 1677
98. M. Nagabhushan, A.J. Amonkar, and S.V. Bhide Mutagenicity of gingerol and shogaol and antimutagenicity of zingerone in Salmonella/microsome assay Cancer Lett. 36 1987 221 233
99. C. Nagoshi, S. Shiota, T. Kuroda, T. Hatano, T. Yoshida, R. Kariyama, and T. Tsuchiya Synergistic effect of [10]-gingerol and aminoglycosides against vancomycin-resistant enterococci (VRE) Biol. Pharm. Bull. 29 2006 443 447
100. H. Nakamura, and T. Yamamoto The active part of the [6]-gingerol molecule in mutagenesis Mutat. Res. Lett. 122 1983 87 94
101. T. Nakazawa, and K. Ohsawa Metabolism of [6]-gingerol in rats Life Sci. 70 2002 2165 2175
102. 2+-ATPase, ameliorate diabetes mellitus-induced diastolic dysfunction in isolated murine ventricular myocardial Eur. J. Pharmacol. 706 2013 48 55
103. K. Naora, G. Ding, M. Hayashibara, Y. Katagiri, Y. Kano, and K. Iwamoto Pharmacokinetics of [6]-gingerol after intravenous administration in rats with acute renal or hepatic failure Chem. Pharm. Bull. 40 1992 1295 1298
104. E.K. Nelson Gingerol and paradol J. Am. Chem. Soc. 39 1917 1466 1469
105. H. Nie, L.Z. Meng, and H. Zhang Effect of gingerol on endotoxemia mouse model induced by heatstroke Chin. J. Integr. Trad. West. Med. 26 2006 529 532
106. N. Nigam, K. Bhui, S. Prasad, J. George, and Y. Shukla [6]-Gingerol induces reactive oxygen species regulated mitochondrial cell death pathway in human epidermoid carcinoma A431 cells Chem. Biol. Interact. 181 2009 77 84
107. N. Nigam, J. George, S. Srivastava, P. Roy, K. Bhui, M. Singh, and Y. Shukla 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 2010 687 696
108. 2+-ATPase by gingerol analogues Biol. Pharm. Bull. 19 1996 1377 1379
109. S. Ok, and W.S. Jeong Optimization of extraction conditions for the 6-shogaol-rich extract from ginger (Zingiber officinale Roscoe) Prevent. Nutr. Food Sci. 17 2012 166 171
110. M. Okamoto, H. Irii, Y. Tahara, H. Ishii, A. Hirao, H. Udagawa, M. Hiramoto, K. Yasuda, A. Takanishi, S. Shibata, and I. Shimizu Synthesis of a new [6]-gingerol analogue and its protective effect with respect to the development of metabolic syndrome in mice fed a high-fat diet J. Med. Chem. 54 2011 6295 6304
111. H. Okumi, K. Tashima, K. Matsumoto, T. Namiki, K. Terasawa, and S. Horie Dietary agonists of TRPV1 inhibit gastric acid secretion in mice Planta Med. 78 2012 1801 1806
112. A.A. Oyagbemi, A.B. Saba, and O.I. Azeez Molecular targets of [6]-gingerol: its potential roles in cancer chemoprevention BioFactors 36 2010 169 178
113. M.H. Pan, M.C. Hsieh, P.C. Hsu, S.Y. Ho, C.S. Lai, H. Wu, S. Sang, and C.T. Ho 6-Shogaol suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages Mol. Nutr. Food Res. 52 2008 1467 1477
114. M.H. Pan, M.C. Hsieh, J.M. Kuo, C.S. Lai, H. Wu, S. Sang, and C.T. Ho 6-Shogaol induces apoptosis in human colorectal carcinoma cells via ROS production, caspase activation, and GADD 153 expression Mol. Nutr. Food Res. 52 2008 527 537
115. J.S. Park, and M.Y. Jung Development of high-performance liquid chromatography-time-of-flight mass spectrometry for the simultaneous characterization and quantitative analysis of gingerol-related compounds in ginger products J. Agric. Food Chem. 60 2012 10015 10026
116. K.K. Park, K.S. Chun, J.M. Lee, S.S. Lee, and Y.J. Surh 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 1998 139 144
117. Y.J. Park, J. Wen, S. Bang, S.W. Park, and S.Y. Song [6]-Gingerol induces cell cycle arrest and cell death of mutant p53-expressing pancreatic cancer cells Yonsei Med. J. 47 2006 688 697
118. M. Park, J. Bae, and D.S. Lee Antibacterial activity of [10]-gingerol and [12]-gingerol isolated from ginger rhizome against periodontal bacteria Phytother. Res. 22 2008 1446 1449
119. S.A. Park, I.H. Park, J.S. Cho, Y.M. Moon, S.H. Lee, T.H. Kim, S.H. Lee, and H.M. Lee Effect of [6]-gingerol on myofibroblast differentiation in transforming growth factor beta 1-induced nasal polyp-derived fibroblasts Am. J. Rhinol. Allergy 26 2012 97 103
120. F. Peng, Q. Tao, X. Wu, H. Dou, S. Spencer, C. Mang, L. Xu, L. Sun, Y. Zhao, H. Li, S. Zeng, G. Liu, and X. Hao Cytotoxic, cytoprotective and antioxidant effects of isolated phenolic compounds from fresh ginger Fitoterapia 83 2012 568 585
121. H.H. Pertz, J. Lehmann, R. Roth-Ehrang, and S. Elz Effects of ginger constituents on the gastrointestinal tract: role of cholinergic M3 and serotonergic 5-HT3 and 5-HT4 receptors Planta Med. 77 2011 973 978
122. M. Rafi, L.W. Lim, T. Takeuchi, and L.K. Darusman Simultaneous determination of gingerols and shogaol using capillary liquid chromatography and its application in discrimination of three ginger varieties from Indonesia Talanta 103 2013 28 32
123. S. Rai, K. Mukherjee, M. Mal, A. Wahile, B.P. Saha, and P.K. Mukherjee Determination of 6-gingerol in ginger (Zingiber officinale) using high-performance thin-layer chromatography J. Sep. Sci. 29 2006 2292 2295
124. M.C. Ramirez-Ahumada, B.N. Timmermann, and D.R. Gang Biosynthesis of curcuminoids and gingerols in turmeric (Curcuma longa) and ginger (Zingiber officinale): identification of curcuminoid synthase and hydroxycinnamoyl-CoA thioesterases Phytochemistry 67 2006 2017 2029
125. K.K. Rout, and S.K. Mishra Efficient and sensitive method for quantitative analysis of 6-gingerol in marketed ayurvedic formulation J. Planar. Chromatogr. - Mod. TLC 22 2009 127 131
126. E.P. Sabina, S.J. Pragasam, S. Kumar, and M. Rasool 6-gingerol, an active ingredient of ginger, protects acetaminophen-induced hepatotoxicity in mice J. Chin. Integr. Med. 9 2011 1264 1269
127. G. Sabitha, C. Srinivas, T.R. Reddy, K. Yadagiri, and J.S. Yadav Synthesis of gingerol and diarylheptanoids Tetrahed. Asym. 22 2011 2124 2133
128. P. Saha, B. Das, and K. Chaudhuri Role of 6-gingerol in reduction of cholera toxin activity in vitro and in vivo Antimicrob. Agents Chemother. 57 2013 4373 4380
129. S. Sang, J. Hong, H. Wu, J. Liu, C.S. Yang, M.H. Pan, V. Badmaev, and C.T. Ho Increased growth inhibitory effects on human cancer cells and anti-inflammatory potency of shogaols from Zingiber officinale relative to gingerols J. Agric. Food Chem. 57 2009 10645 10650
130. X. Shao, L. Lv, T. Parks, H. Wu, C.T. Ho, and S. Sang Quantitative analysis of ginger components in commercial products using liquid chromatography with electrochemical array detection J. Agric. Food Chem. 58 2010 12608 12614
131. A. Sharma, S. Sankaranarayanan, and S. Chattopadhyay A chemoenzymatic synthesis of (R)-[8]-gingerol Enantiomer 3 1998 45 50
132. Y. Shukla, S. Prasad, C. Tripathi, M. Singh, J. George, and N. Kalra In vitro and in vivo modulation of testosterone mediated alterations in apoptosis related proteins by [6]-gingerol Mol. Nutr. Food Res. 51 2007 1492 1502
133. J.A.D. Silva, A.B. Becceneri, H.S. Mutti, A.C.B.M. Martin, M.F.D. Silva, J.B. Fernandes, P.C. Vieira, and M.R. Cominetti Purification and differential biological effects of ginger-derived substances on normal and tumor cell lines J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 903 2012 157 162
134. G. Solladie, and C. Ziani-Cherif Total synthesis of natural gingerols, the three active principles of ginger J. Org. Chem. 58 1993 2181 2185
135. A. Someya, S. Horie, H. Yamamoto, and T. Murayama Modification of capsaicin-sensitive neurons in isolated guinea pig ileum by [6]-gingerol and lafutidine J. Pharmacol. Sci. 92 2003 359 366
136. M. Suekawa, A. Ishige, K. Yuasa, K. Sudo, M. Aburada, and E. Hosoya Pharmacological studies on ginger. I. Pharmacological actions of pungent constituents, (6)-gingerol and (6)-shogaol J. Pharmacobiodyn. 7 1984 836 848
137. Y.J. Surh, and S.S. Lee Enzymic reduction of [6]-gingerol, a major pungent principle of ginger, in the cell-free preparation of rat liver Life Sci. 54 1994 321 326
138. Y.-J. Surh, K.-K. Park, K.-S. Chun, J.-M. Lee, E. Lee, and S.S. Lee Anti-tumor-promoting activities of selected pungent phenolic substances present in ginger J. Environ. Pathol. Toxicol. Oncol. 18 1999 131 139
139. H. Takahashi, T. Hashimoto, Y. Noma, and Y. Asakawa Biotransformation of 6-gingerol and 6-shogaol by Aspergillus niger Phytochemistry 34 1993 1497 1500
140. B.S. Tan, O. Kang, C.W. Mai, K.H. Tiong, A.S.B. Khoo, M.R. Pichika, T.D. Bradshaw, and C.O. Leong 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor γ (PPARγ) Cancer Lett. 336 2013 127 139
141. J.C. Thresh Proximate analysis of the rhizome of Zingiber officinale and comparitive examination of typical specimens of commercial gingers Pharm. J. 10 1879 171
142. I. Tintu, K.V. Dileep, C. Remya, A. Augustine, and C. Sadasivan 6-Gingerol inhibits fungal alpha amylase: enzyme kinetic and molecular modeling studies Starch-Staerke 64 2012 607 612
143. E.A. Townsend, M.E. Siviski, Y. Zhang, C. Xu, B. Hoonjan, and C.W. Emala Effects of ginger and its constituents on airway smooth muscle relaxation and calcium regulation Am. J. Respir. Cell Mol. Biol. 48 2013 157 163
144. S. Tripathi, K.G. Maier, D. Bruch, and D.S. Kittur Effect of 6-gingerol on pro-inflammatory cytokine production and costimulatory molecule expression in murine peritoneal macrophages J. Surg. Res. 138 2007 209 213
145. O. Tsuge, S. Kanemasa, N. Nakagawa, and H. Suga Horner-Emmons olefination of 4-hydroxy-2-oxoalklyphosphonates and related compounds: applications to the syntheses of (±)-gingerol, (±)-yashabushiketol, and (±)-dihydroyashabushiketol Bull. Chem. Soc. Jpn. 60 1987 4091 4098
146. T.F. Tzeng, and I.M. Liu 6-Gingerol prevents adipogenesis and the accumulation of cytoplasmic lipid droplets in 3T3-L1 cells Phytomedicine 20 2013 481 487
147. S. Ueki, M. Miyoshi, O. Shido, J. Hasegawa, and T. Watanabe Systemic administration of [6]-gingerol, a pungent constituent of ginger, induces hypothermia in rats via an inhibitory effect on metabolic rate Eur. J. Pharmacol. 584 2008 87 92
148. W.H. Wang, Z.M. Wang, L.Z. Xu, and S.L. Yang HPLC determination of 6-gingerol in Rhizoma Zingiberis Recens China J. Chin. Mat. Med. 27 2002 342 349
149. C.C. Wang, L.G. Chen, L.T. Lee, and L.L. Yang Effects of 6-gingerol, an antioxidant from ginger, on inducing apoptosis in human leukemic HL-60 cells In Vivo 17 2003 641 645
150. W. Wang, C.Y. Li, X.D. Wen, P. Li, and L.W. Qi 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. 49 2009 1070 1074
151. Z. Wang, K.J. Wang, C.S. Cheng, N. Li, T.M. Wang, and L. Di Gingerol derivatives from the rhizomes of Zingiber officinale Z. Naturforsch. B 66 2011 740 744
152. X. Wang, Z. Zheng, X. Guo, J. Yuan, and C. Zheng Preparative separation of gingerols from Zingiber officinale by high-speed counter-current chromatography using stepwise elution Food Chem. 125 2011 1476 1480
153. M.L. Wang, Y.L. Yang, Z.X. Wei, W. Yue, and W.Q. Xu The effect of gingerol on cisplatin-induced pica in rats Chin. Pharmacol. Bull. 28 2012 558 562
154. C.J. Weng, C.F. Wu, H.W. Huang, C.T. Ho, and G.C. Yen Anti-invasion effects of 6-shogaol and 6-gingerol, two active components in ginger, on human hepatocarcinoma cells Mol. Nutr. Food Res. 54 2010 1618 1627
155. C.J. Weng, C.P. Chou, C.T. Ho, and G.C. Yen Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol Mol. Nutr. Food Res. 56 2012 1304 1314
156. Wohlmuth, H., 2008. Phytochemistry and Pharmacology of Plants from the Ginger Family, Zingiberaceae (PhD thesis). Southern Cross University, Lismore, NSW.
157. H. Wohlmuth, D.N. Leach, M.K. Smith, and S.P. Myers Gingerol content of diploid and tetraploid clones of ginger (Zingiber officinale Roscoe) J. Agric. Food Chem. 53 2005 5772 5778
158. H. Wu, M.C. Hsieh, C.Y. Lo, C.B. Liu, S. Sang, C.T. Ho, and M.H. Pan 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. 54 2010 1296 1306
159. S. Yagihashi, Y. Miura, and K. Yagasaki Inhibitory effect of gingerol on the proliferation and invasion of hepatoma cells in culture Cytotechnology 57 2008 129 136
160. J. Yamahara, H. Matsuda, S. Yamaguchi, H. Shimoda, N. Murakami, and M. Yoshikawa Pharmacological study on ginger processing. I. Antiallergic activity and cardiotonic action of gingerols and shogaols Nat. Med. 49 1995 76 83
161. G. Yang, L. Zhong, L. Jiang, C. Geng, J. Cao, X. Sun, and Y. Ma Genotoxic effect of 6-gingerol on human hepatoma G2 cells Chem. Biol. Interact. 185 2010 12 17
162. G. Yang, L. Zhong, L. Jiang, C. Geng, J. Cao, X. Sun, X. Liu, M. Chen, and Y. Ma 6-gingerol prevents patulin-induced genotoxicity in HepG2 cells Phytother. Res. 25 2011 1480 1485
163. G. Yang, S. Wang, L. Zhong, X. Dong, W. Zhang, L. Jiang, C. Geng, X. Sun, X. Liu, M. Chen, and Y. Ma 6-gingerol induces apoptosis through lysosomal-mitochondrial axis in human hepatoma G2 cells Phytother. Res. 26 2012 1667 1673
164. 2+]i and cell death in human colorectal cancer cells Molecules 14 2009 959 969
165. J.M. Yon, I.J. Baek, B.J. Lee, Y.W. Yun, and S.Y. Nam Emodin and [6]-gingerol lessen hypoxia-induced embryotoxicities in cultured mouse whole embryos via upregulation of hypoxia-inducible factor 1α and intracellular superoxide dismutases Reprod. Toxicol. 31 2011 513 518
166. J.M. Yon, I.J. Baek, S.R. Lee, M.R. Kim, J.T. Hong, H. Yong, B.J. Lee, Y.W. Yun, and S.Y. Nam Protective effect of [6]-gingerol on the ethanol-induced teratogenesis of cultured mouse embryos Arch. Pharm. Res. 35 2012 171 178
167. H.Y. Young, Y.L. Luo, H.Y. Cheng, W.C. Hsieh, J.C. Liao, and W.H. Peng Analgesic and antiinflammatory activities of [6]-gingerol J. Ethnopharmacol. 96 2005 207 210
168. H.L. Zeng, X.A. Han, C. Gu, X.S. Huang, J.Q. Gu, Q. Zhong, W.J. Ming, and X.N. Cai Comparative protein analysis of K562 cell apoptosis induced by 6-gingerol J. Chin. Med. Mater. 33 2010 753 758
169. H.L. Zeng, X.A. Han, C. Gu, H.Y. Zhu, X.S. Huang, J.Q. Gu, Q. Zhong, G.J. Liu, W.J. Ming, and X.N. Cai Reactive oxygen species and mitochondrial membrane potential changes in leukemia cells during 6-gingerol induced apoptosis J. Chin. Med. Mater. 33 2010 584 587
170. K. Zhan, K. Xu, and H. Yin Preparative separation and purification of gingerols from ginger (Zingiber officinale Roscoe) by high-speed counter-current chromatography Food Chem. 126 2011 1959 1963
171. Y.X. Zhang, J.S. Li, L.H. Chen, W.W. Peng, and B.C. Cai Simultaneous determination of five gingerols in raw and processed ginger by HPLC Chin. Pharm. J. 47 2012 471 474
172. Y.L. Zhang, Y.M. Zheng, S.N. Hu, and H. Liu Anti-Helicobacter pylori effect of 6-gingerol in vitro Modern Food Sci. Technol. 29 2013 1259 1261
173. Zhu, P.H., 2009. Immunomodulation Effect of Gingerol on Immunosuppression Induced via Gamma-Ray Radiation in the Kunming Mice (Master's thesis). Sichuan Agricultural University, China.
174. S.M. Zick, Z. Djuric, M.T. Ruffin, A.J. Litzinger, D.P. Normolle, S. Alrawi, M.R. Feng, and D.E. Brenner Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects Cancer Epidemiol. Biomark. Prev. 17 2008 1930 1936