Gingerols: A novel class of vanilloid receptor (VR1) agonists

British Journal of Pharmacology

Volumn 137, Issue 6, 2002, Pages 793-798

  Dedov, Vadim N ^a   Tran, Van H ^a   Duke, Colin C ^a   Connor, Mark ^b   Christie, MacDonald J ^b   Mandadi, Sravan ^a   Roufogalis, Basil D ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

^b University of Sydney   (Australia)

Author keywords

DRG neurones; Ginger; Gingerols; Intracellular calcium; Plasma membrane currents; VR1 receptor

Indexed keywords

6 GINGEROL; 8 GINGEROL; CALCIUM ION; CAPSAICIN; CAPSAZEPINE; GINGEROL; NERVE GROWTH FACTOR; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG; VANILLOID RECEPTOR; VANILLOID RECEPTOR 1; VANILLOID RECEPTOR AGONIST;

ANIMAL CELL; ARTICLE; CALCIUM CELL LEVEL; CONTROLLED STUDY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; HYDROPHOBICITY; MEMBRANE CURRENT; NERVE CELL; NOCICEPTION; NONHUMAN; PAIN; PATCH CLAMP; PRIORITY JOURNAL; RAT; SPINAL GANGLION;

ANIMALS; ANIMALS, NEWBORN; CALCIUM; CAPSAICIN; CELLS, CULTURED; DOSE-RESPONSE RELATIONSHIP, DRUG; FATTY ALCOHOLS; FURA-2; GANGLIA, SPINAL; MEMBRANE POTENTIALS; NEURONS; RATS; RECEPTORS, DRUG; TIME FACTORS;

EID: 0036856241     PISSN: 00071188     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.bjp.0704925     Document Type: Article

References (39)

1. Blumenthal, M. & Werner, B.R. (1998). The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, Tex.: American Botanical Council; Boston, MA.: Integrative Medicine Communications.
2. Caterina, M.J., Schumacher, M.A., Tominaga, M. Rosen, T.A., Levine, J.D. & Julius, D. (1997). The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature, 389, 816-824.
3. Caterina, M.J., Leffler, A., Malmberg, A.B., Martin, W.J., Trafton, J., Petersen-Zeitz, K.R., Koltzenburg, M., Basbaum, A.I. & Julius, D. (2000). Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science, 288, 306-313.
4. Chard, P.S., Bleakman, D., Savidge, J.R. & Miller, R.J. (1995). Capsaicin-induced neurotoxicity in cultured dorsal root ganglion neurons: Involvement of calcium-activated proteases. Neuroscience, 65, 1099-1108.
5. Cholewinski, A., Burgess, G.M. & Bevan, S. (1993). The role of calcium in capsaicin-induced desensitization in rat cultured dorsal root ganglion neurons. Neuroscience, 55, 1015-1023.
6. Craib, S.J., Ellington, H.C., Pertwee, R.G. & Ross, R.A. (2001) A possible role of lipoxygenase in the activation of vanilloid receptors by anandamide in the guinea-pig bronchus. Br. J. Pharmacol., 134, 30-37.
7. 2+. Neurosci. Lett., 248, 151-154.
8. Dedov, V.N. & Roufogalis, B.D. (2000). Mitochondrial calcium accumulation following activation of vanilloid (VR1) receptors by capsaicin in dorsal root ganglion neurons. Neuroscience. 95, 183-188.
9. Denniff, P., Macleod, I. & Whiting, D.A. (1981). 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, 82-87.
10. Ernst, E. & Pittler, M.H. (2000). Efficacy of ginger for nausea and vomiting: A systematic review of randomised clinical trials. Br. J. Anaesth., 84, 367-371.
11. Grant, K.L. & Lutz, R.B., (2000). Ginger. Am. J. Health Syst. Pharm., 57, 945-947.
12. 2+ indicators with greatly improved fluorescence properties. J. Biol. Chem., 260, 3440-3450.
13. Huang, S.M., Bisogno, T., Trevisani, M., Al-Hayani, A., De Petrocellis, L., Fezza, F., Tognetto, M., Petros, T.J., Krey, J.F., Chu, C.J., Miller, J.D., Davies, S.N., Geppetti, P., Walker, J.M. & Di Marzo, V. (2002) An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc. Natl. Acad. Sci, U.S.A., 99, 8400-8405.
14. Hwang, S.W., Cho, H., Kwak, J., Lee, S-Y., Kang, C-J., Jung, J., Cho, S., Min, K.H., Suh, Y-G., & Oh, U. (2000). Direct activation of capsaicin receptors by products of lipoxygenases: Endogenous capsaicin-like substances. Proc. Natl. Acad. Sci. U.S.A., 97, 6155-6160.
15. 2+] with fluorescent indicators. Methods Cell Biol., 40, 155-181.
16. Kiuchi, F., Iwakami, S., Shibuya, M., Hanaoka, F. & Sankawa, U. (1982). Inhibitors of prostaglandin biosynthesis from ginger. Chem. Pharm. Bull., 30, 754-757.
17. 2+ channels in isolated rat trigeminal and hippocampal neurons, NeuroReport, 6, 2338-2340.
18. 2+ influx through the plasmalemma. In Calcium Signaling in the Nervous System. pp 1-38. Chichester; New York: J. Wiley and Sons.
19. Kress, M. & Zeilhofer, H.U. (1999). Capsaicin, protons and heat: New excitement about nociceptors. Trends Pharmacol. Sci., 20, 112-118.
20. Liu, L. & Simon, S.A. (1996). Similarities and differences in the currents activated by capsaicin, piperine, and zingerone in rat trigeminal ganglion cells. J. Neurophysiol., 76, 1858-1869.
21. Mascolo, N., Jain, R., Jain, S.C. & Capasso, F. (1989). Ethnopharmacologic investigation of ginger (Zingiber officinale). J. Ethnopharmacol., 17, 129-140.
22. Mezey, E., Toth, Z.E., Cortright, D.N., Arzubi, M.K., Krause, J.E., Elde, R., Guo, A., Blumberg, P.M. & Szallasi, A. (2000). Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc. Natl. Acad. Sci. U.S.A., 97, 3655-3660.
23. Mustafa, T., Srivastava, K.C. & Jensen, K.B. (1993). Drug development report: 9. Pharmacology of ginger, Zingiber officinale. J. Drug Dev., 6, 25-39.
24. Nolano, M., Simone, D.A., Wendelschafer-Crabb, G., Johnson, T., Hazen, E. & Kennedy, W.R. (1999). Topical capsaicin in humans: Parallel loss of epidermal nerve fibers and pain sensation. Pain, 81, 135-145.
25. Olah, Z., Karai, L. & Iadarola, M.J. (2001). Anandamide activates vanilloid receptor 1 (VR1) at acidic pH in dorsal root ganglia neurons and cells ectopically expressing VR1. J. Biol. Chem., 276, 31163-31170.
26. Piomelli, D. (2001). The ligand that came from within. Trends Pharmacol. Sci., 22, 17-19.
27. Piper, A.S., Yeats, J.C., Bevan, S. & Docherty, R.J. (1999). A study of the voltage dependence of capsaicin-activated membrane currents in rat sensory neurones before and after acute desensitization. J. Physiol., 518, 721-733.
28. Roufogalis, B.D. & Dedov, V.N. (1999). Capsaicin receptor mechanism and future trends for analgesics. In Herbal Medicinal Products for the Treatment of Pain. ed. Chrubasik, S. & Roufogalis, B.D. pp 94-98. Lismore: Southern Cross University Press.
29. Szallasi, A., Biro, T., Modarres, S., Garlaschelli, L., Petersen, M., Klusch, A., Vidari, G., Jonassohn, M., De Rosa, S., Sterner, O., Blumberg, P.M. & Krause, J.E. (1998). Dialdehyde sesquiterpenes and other terpenoids as vanilloids. Eur. J. Pharmacol., 356, 81-89.
30. Sharma, H. & Clark, C. (1998). Active ingredients, free radicals and the herbal pharmacopeia. In Contemporary Ayurveda: Medicine and Research in Maharishi Ayur-Veda. 75-95. New York: Churchill Livingstone.
31. Smart, D., & Jerman, J.C. (2000). Anandamide: An endogenous activator of the vanilloid receptor. Trends Pharmacol. Sci., 21, 134.
32. Smart, D., Gunthorpe, M.J., Jerman, J.C., Nasir, S., Gray, J., Muir, A.I., Chambers, J.K., Randall, A.D. & Davis, J.B. (2000). The endogenous lipid anandamide is full agonist at the human vanilloid receptor (hVR1). Br. J. Pharmacol., 129, 227-230.
33. Srivastava, K.C. & Mustafa, T. (1992). Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. Med. Hypotheses, 39, 342-348.
34. Tominaga, M., Caterina, M.J., Malmberg, A.B., Rosen, T.A., Gilbert, H., Skinner, K., Raumann, B.E., Basbaum, A.I. & Julius, D. (1998). The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron, 21, 531-543.
35. Walpole, C.S.J., Wrigglesworth, R., Bevan, S., Campbell, E.A., Dray, A., James I.F., Perkins, M.N., Reid, D.J. & Winter, J. (1993a). Analogues of capsaicin with agonist activity as novel analgesic agents; Structure-activity studies: 1. The Aromatic 'A-region'. J. Med. Chem., 36, 2362-2372.
36. Walpole, C.S.J., Wrigglesworth, R., Bevan, S., Campbell, E.A., Dray, A., James I.F., Masdin, K.J., Perkins, M.N. & Winter, J. (1993b). Analogues of capsaicin with agonist activity as novel analgesic agents; Structure-activity studies: 2. The amide bond 'B-region'. J. Med. Chem., 36, 2373-2380.
37. Walpole, C.S.J., Wrigglesworth, R., Bevan, S., Campbell, E.A., Dray A., James, I.F., Masdin, K.J., Perkins, M.N. & Winter, J. (1993c). Analogues of capsaicin with agonist activity as novel analgesic agents; Structure-activity studies: 3. The hydrophobic side-chain 'C-region'. J. Med. Chem., 36, 2381-2389.
38. Wood, J.N. (ed.). (1993). Capsaicin in the Study of Pain. New York: Academic press.
39. Zygmunt, P.M., Petersson, J., Andersson, D.A., Chuang, H.H., Sorgard, M., Di Marzo, V., Julius, D. & Hogestatt, E.D. (1999). Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature. 400, 452-457.