Functionalization of β-caryophyllene generates novel polypharmacology in the endocannabinoid system

ACS Chemical Biology

Volumn 9, Issue 7, 2014, Pages 1499-1507

  Chicca, Andrea ^a   Caprioglio, Diego ^b   Minassi, Alberto ^b   Petrucci, Vanessa ^a   Appendino, Giovanni ^b   Taglialatela Scafati, Orazio ^c   Gertsch, Jürg ^a  

^a UNIVERSITY OF BERN   (Switzerland)

^b UNIVERSITY OF EASTERN PIEDMONT   (Italy)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ACRYLIC ACID ETHYL ESTER; ARACHIDONIC ACID; CANNABINOID 2 RECEPTOR; CARYOPHYLLENE; ENDOCANNABINOID; SESQUITERPENE; AMIDASE; CYCLOOXYGENASE 2 INHIBITOR; FATTY-ACID AMIDE HYDROLASE; NONSTEROID ANTIINFLAMMATORY AGENT;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; BINDING ASSAY; CARBON NUCLEAR MAGNETIC RESONANCE; CONTROLLED STUDY; CYCLIZATION; CYCLOPROPANATION; ENZYMATIC DEGRADATION; ENZYME ACTIVITY; EPOXIDATION; HUMAN; HYDROLYSIS; ISOMER; NONHUMAN; PHARMACOPHORE; POLYPHARMACOLOGY; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; RECEPTOR BINDING; RECEPTOR BINDING ASSAY; AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; CHO CELL LINE; CRICETULUS; EUGENIA; METABOLISM;

AMIDOHYDROLASES; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CHO CELLS; CRICETULUS; CYCLOOXYGENASE 2 INHIBITORS; ENDOCANNABINOIDS; EUGENIA; HUMANS; POLYPHARMACOLOGY; RECEPTOR, CANNABINOID, CB2; SESQUITERPENES;

EID: 84904549118     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb500177c     Document Type: Article

References (57)

1. Hanson, J. R. (2001) The development of strategies for terpenoid structure determination Nat. Prod. Rep. 18, 607-617 (Pubitemid 34010014)
2. Corey, E. J., Mitra, R. B., and Uda, H. (1964) Total Synthesis of d, l -caryophyllene and d, l -isocaryophyllene J. Am. Chem. Soc. 86, 485-492
3. Collado, I. G., Hanson, J. R., and Macias-Sanchez, A. J. (1998) Recent advances in the chemistry of caryophyllene Nat. Prod. Rep. 15, 187-204 (Pubitemid 28202598)
4. Gertsch, J., Leonti, M., Raduner, S., Racz, I., Chen, J. Z., Xie, X. Q., Altmann, K. H., Karsak, M., and Zimmer, A. (2008) Beta-caryophyllene is a dietary cannabinoid Proc. Natl. Acad. Sci. U.S.A. 105, 9099-9104
5. Paula-Freire, L. I., Andersen, M. L., Gama, V. S., Molska, G. R., and Carlini, E. L. (2014) The oral administration of trans-caryophyllene attenuates acute and chronic pain in mice Phytomedicine 21, 356-362
6. Gertsch, J. (2008) Anti-inflammatory cannabinoids in diet: Towards a better understanding of CB(2) receptor action? Commun. Integr. Biol. 1, 26-28
7. Gane, S., Georganakis, D., Maniati, K., Vamvakias, M., Ragoussis, N., Skoulakis, E. M., and Turin, L. (2013) Molecular vibration-sensing component in human olfaction PLoS One 8, e55780
8. Appendino, G., Chianese, G., and Taglialatela-Scafati, O. (2011) Cannabinoids: occurrence and medicinal chemistry Curr. Med. Chem. 18, 1086-1099
9. 2 ligands for drug abuse and their therapeutic potential Future Med. Chem. 4, 187-204
10. Horváth, B., Mukhopadhyay, P., Kechrid, M., Patel, V., Tanchian, G., Wink, D. A., Gertsch, J., and Pacher, P. (2012) β-Caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner Free Radicals Biol. Med. 52, 1325-1333
11. 2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain Eur. Neuropsychopharmacol. 24, 608-620
12. Choi, I. Y., Ju, C., Anthony Jalin, A. M., Lee, D. I., Prather, P. L., and Kim, W. K. (2013) Activation of cannabinoid CB2 receptor-mediated AMPK/CREB pathway reduces cerebral ischemic injury Am. J. Pathol. 182, 928-939
13. Bento, A. F., Marcon, R., Dutra, R. C., Claudino, R. F., Cola, M., Leite, D. F., and Calixto, J. B. (2011) β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway Am. J. Pathol. 178, 1153-1166
14. Leleu-Chavain, N., Body-Malapel, M., Spencer, J., Chavatte, P., Desreumaux, P., and Millet, R. (2012) Recent advances in the development of selective CB(2) agonists as promising anti-inflammatory agents Curr. Med. Chem. 19, 3457-3474
15. Pacher, P. and Mechoulam, R. (2011) Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog. Lipid Res. 50, 193-211
16. Steffens, S. and Pacher, P. (2012) Targeting cannabinoid receptor CB(2) in cardiovascular disorders: promises and controversies Br. J. Pharmacol. 167, 313-323
17. Barton, D. H. R., Bruun, T., and Lindsey, A. S. (1952) Tricyclic derivatives of caryophyllene J. Chem. Soc. 2210-2219
18. Rao, V. V. R. and Devaprabhakara, D. (1978) Tetrahedron 34, 2223
19. 2-selective ligands FEBS Lett. 580, 568-574 (Pubitemid 43089687)
20. Allen, F. H., Brown, E. D., Rogers, D., and Sutherland, J. K. (1967) Structure and reactivity in medium-ring olefins Chem. Commun. (London) 1116-1118
21. Cope, A. C., Martin, M. M., and McKervey, M. A. (1966) Transannular reactions in medium.sized rings Q. Rev., Chem. Soc. 20, 119-152
22. Morgan, J. P., Morrill, C., and Grubbs, R. H. (2002) Selective ring opening cross metathesis of cyclooctadiene and trisubstituted cycloolefins Org. Lett. 4, 67-70
23. Gertsch, J. (2008) Immunomodulatory lipids in plants: plant fatty acid amides and the human endocannabinoid system Planta Med. 74, 638-650 (Pubitemid 351846778)
24. Appendino, G., Minassi, A., Morello, A. S., De Petrocellis, L., and Di Marzo, V. (2002) N -Acylvanillamides: Development of an expeditious synthesis and discovery of new acyl templates for powerful activation of the vanilloid receptor J. Med. Chem. 45, 3739-3745 (Pubitemid 34856112)
25. Maione, S., Costa, B., and Di Marzo, V. (2013) Endocannabinoids: a unique opportunity to develop multitarget analgesics Pain 154, S87-93
26. Pertwee, R. G. (2013) Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications Proc. Nutr. Soc. 18, 1-10
27. Cravatt, B. F., Giang, D. K., Mayfield, S. P., Boger, D. L., Lerner, R. A., and Gilula, N. B. (1996) Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides Nature 384, 83-87 (Pubitemid 26374593)
28. Kathuria, S., Gaetani, S., Fegley, D., Valiño, F., Duranti, A., Tontini, A., Mor, M., Tarzia, G., La Rana, G., Calignano, A., Giustino, A., Tattoli, M., Palmery, M., Cuomo, V., and Piomelli, D. (2003) Modulation of anxiety through blockade of anandamide hydrolysis Nat. Med. 9, 76-81 (Pubitemid 36098263)
29. Long, J. Z., Li, W., Booker, L., Burston, J. J., Kinsey, S. G., Schlosburg, J. E., Pavón, F. J., Serrano, A. M., Selley, D. E., Parsons, L. H., Lichtman, A. H., and Cravatt, B. F. (2009) Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioural effects Nat. Chem. Biol. 5, 37-44
30. Blankman, J. L., Simon, G. M., and Cravatt, B. F. (2007) A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2- arachidonoylglycerol Chem. Biol. 14, 1347-1356 (Pubitemid 350257008)
31. Marrs, W. R., Blankman, J. L., Horne, E. A., Thomazeau, A., Lin, Y. H., Coy, J., Bodor, A. L., Muccioli, G. G., Hu, S. S., Woodruff, G., Fung, S., Lafourcade, M., Alexander, J. P., Long, J. Z., Li, W., Xu, C., Möller, T., Mackie, K., Manzonim, O. J., Cravatt, B. F., and Stella, N. (2010) The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors Nat. Neurosci. 13, 951-957
32. Chicca, A., Marazzi, J., and Gertsch, J. (2012) The antinociceptive triterpene β-amyrin inhibits 2-arachidonoylglycerol (2-AG) hydrolysis without directly targeting cannabinoid receptors Br. J. Pharmacol. 167, 1596-1608
33. Kozak, K. R., Rowlinson, S. W., and Marnett, L. J. (2000) Oxygenation of the endocannabinoid, 2-arachidonylglycerol, to glyceryl prostaglandins by cyclooxygenase-2 J. Biol. Chem. 275, 3344-3349
34. Kozak, K. R., Crews, B. C., Morrow, J. D., Wang, L. H., Ma, Y. H., Weinander, R., Jakobsson, P. J., and Marnett, L. J. (2002) Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides J. Biol. Chem. 277, 44877-44885 (Pubitemid 36159083)
35. Woodward, D. F., Carling, R. W., Cornell, C. L., Fliri, H. G., Martos, J. L., Pettit, S. N., Liang, Y., and Wang, J. W. (2008) The pharmacology and therapeutic relevance of endocannabinoid derived cyclo-oxygenase (COX)-2 products Pharmacol. Ther. 120, 71-80
36. Liang, Y., Woodward, D. F., Guzman, V. M., Li, C., Scott, D. F., Wang, J. W., Wheeler, L. A., Garst, M. E., Landsverk, K., Sachs, G., Krauss, A. H., Cornell, C., Martos, J., Pettit, S., and Fliri, H. (2008) Identification and pharmacological characterization of the prostaglandin FPreceptor and FP receptor variant complexes Br. J. Pharmacol. 154, 1079-1093 (Pubitemid 351915050)
37. Gatta, L., Piscitelli, F., Giordano, C., Boccella, S., Lichtman, A., Maione, S., and Di Marzo, V. (2012) Discovery of prostamide F2α and its role in inflammatory pain and dorsal horn nociceptive neuron hyperexcitability PLoS One 7, e31111
38. Chicca, A., Marazzi, J., Nicolussi, S., and Gertsch, J. (2012) Evidence for bidirectional endocannabinoid transport across cell membranes J. Biol. Chem. 287, 34660-34682
39. Nomura, D. K., Morrison, B. E., Blankman, J. L., Long, J. Z., Kinsey, S. G., Marcondes, M. C., Ward, A. M., Hahn, Y. K., Lichtman, A. H., Conti, B., and Cravatt, B. F. (2011) Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation Science 334, 809-813
40. Kuc, C., Jenkins, A., and Van Dross, R. T. (2012) Arachidonoyl ethanolamide (AEA)-induced apoptosis is mediated by J-series prostaglandins and is enhanced by fatty acid amide hydrolase (FAAH) blockade Mol. Carcinog. 51, 139-149
41. Fowler, C. J., Naidu, P. S., Lichtman, A., and Onnis, V. (2009) The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1 Br. J. Pharmacol. 156, 412-419
42. Fowler, C. J., Tiger, G., and Stenström, A. (1997) Ibuprofen inhibits rat brain deamidation of anandamide at pharmacologically relevant concentrations. Mode of inhibition and structure-activity relationship J. Pharmacol. Exp. Ther. 283, 729-734 (Pubitemid 27514633)
43. Holt, S., Paylor, B., Boldrup, L., Alajakku, K., Vandevoorde, S., Sundström, A., Cocco, M. T., Onnis, V., and Fowler, C. J. (2007) Inhibition of fatty acid amide hydrolase, a key endocannabinoid metabolizing enzyme, by analogues of ibuprofen and indomethacin Eur. J. Pharmacol. 565, 26-36 (Pubitemid 46782775)
44. Weber, A., Ni, J., Ling, K. H., Acheampong, A., Tang-Liu, D. D., Burk, R., Cravatt, B. F., and Woodward, D. (2004) Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry J. Lipid. Res. 45, 757-763 (Pubitemid 38405683)
45. Wahli, W. and Michalik, L. (2012) PPARs at the crossroads of lipid signaling and inflammation Trends Endocrinol. Metab. 23, 351-363
46. Sinning, C., Watzer, B., De Petrocellis, L., Di Marzo, V., and Imming, P. (2008) Dopamides, vanillylamides, ethanolamides, and arachidonic acid amides of anti-inflammatory and analgesic drug substances as TRPV1 ligands ChemMedChem. 3, 1956-1964
47. Brooks, J. W., Pryce, G., Bisogno, T., Jaggar, S. I., Hankey, D. J., Brown, P., Bridges, D., Ledent, C., Bifulco, M., Rice, A. S., Di Marzo, V., and Baker, D. (2002) Arvanil-induced inhibition of spasticity and persistent pain: evidence for therapeutic sites of action different from the vanilloid VR1 receptor and cannabinoid CB(1)/CB(2) receptors Eur. J. Pharmacol. 439, 83-92 (Pubitemid 34286610)
48. Di Marzo, V., Blumberg, P. M., and Szallasi, A. (2002) Endovanilloid signaling in pain Curr. Opin. Neurobiol. 12, 372-379 (Pubitemid 34876481)
49. Maffei, M. E., Gertsch, J., and Appendino, G. (2011) Plant volatiles: production, function and pharmacology Nat. Prod. Rep. 28, 1359-1380
50. Petrelli, A. (2012) Polypharmacological Kinase Inhibitors: New Hopes for Cancer Therapy, in Polypharmacology in Drug Discovery (Peters, J.-U., Ed.), pp 149-165, Wiley, Hoboken.
51. Astarita, G., Geaga, J., Ahmed, F., and Piomelli, D. (2009) Targeted lipidomics as a tool to investigate endocannabinoid function Int. Rev. Neurobiol. 85, 35-55
52. Reddy, A. S. and Zhang, S. (2013) Polypharmacology: drug discovery for the future Expert Rev. Clin. Pharmacol. 6, 41-47
53. Hopkins, A. L. (2008) Network pharmacology: the next paradigm in drug discovery Nat. Chem. Biol. 4, 682-690
54. Bauer, M., Chicca, A., Tamborrini, M., Eisen, D., Lerner, R., Lutz, B., Poetz, O., Pluschke, G., and Gertsch, J. (2012) Identification and quantification of a new family of peptide endocannabinoids (Pepcans) showing negative allosteric modulation at CB1 receptors J. Biol. Chem. 287, 36944-36967
55. Marazzi, J., Kleyer, J., Paredes, J. M., and Gertsch, J. (2011) Endocannabinoid content in fetal bovine sera-unexpected effects on mononuclear cells and osteoclastogenesis J. Immunol. Methods. 373, 219-228
56. King, A. R., Dotsey, E. Y., Lodola, A., Jung, K. M., Ghomian, A., Qiu, Y., Fu, J., Mor, M., and Piomelli, D. (2009) Discovery of potent and reversible monoacylglycerol lipase inhibitors Chem. Biol. 16, 1045-1052
57. Nicolussi, S., Viveros-Paredes, J. M., Gachet, M. S., Rau, M., Flores-Soto, M. E., Blunder, M., and Gertsch, J. (2014) Guineensine is a novel inhibitor of endocannabinoid uptake showing cannabimimetic behavioral effects in BALB/c mice Pharmacol. Res. 80C, 52-65