The antinociceptive triterpene β-amyrin inhibits 2- arachidonoylglycerol (2-AG) hydrolysis without directly targeting cannabinoid receptors

British Journal of Pharmacology

Volumn 167, Issue 8, 2012, Pages 1596-1608

  Chicca, A ^a   Marazzi, J ^a   Gertsch, J ^a  

^a UNIVERSITY OF BERN   (Switzerland)

Author keywords

2 AG; amyrin; CB1 receptor; endocannabinoid system; hydrolases; monoacyl glycerol lipase; pristimerin; triterpene

Indexed keywords

2 ARACHIDONOYLGLYCEROL; ACYLGLYCEROL LIPASE; ALPHA AMYRIN; ANANDAMIDE; BETA AMYRIN; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; FATTY ACID AMIDASE; HYDROLASE; PRISTIMERIN;

ANIMAL CELL; ARTICLE; BINDING ASSAY; BRAIN HOMOGENATE; CELL FREE SYSTEM; CHO CELL; CONTROLLED STUDY; DRUG MECHANISM; DRUG RECEPTOR BINDING; HUMAN; HUMAN CELL; HYDROLYSIS; INHIBITION KINETICS; LIGAND BINDING; NONHUMAN; PRIORITY JOURNAL; SWINE;

AMIDOHYDROLASES; ANALGESICS; ANIMALS; ARACHIDONIC ACIDS; BRAIN; CHO CELLS; CRICETINAE; CRICETULUS; ENDOCANNABINOIDS; GLYCERIDES; HUMANS; HYDROLYSIS; MONOACYLGLYCEROL LIPASES; OLEANOLIC ACID; POLYUNSATURATED ALKAMIDES; RECEPTOR, CANNABINOID, CB1; RECEPTOR, CANNABINOID, CB2; SWINE; U937 CELLS;

EID: 84867386846     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2012.02059.x     Document Type: Article

References (51)

1. Ahn K, McKinney MK, Cravatt BF, (2008). Enzymatic pathways that regulate endocannabinoid signaling in the nervous system. Chem Rev 108: 1687-1707.
2. Akihisa T, Yasukawa K, Oinuma H, Kasahara Y, Yamanouchi S, Takido M, et al,. (1996). Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects. Phytochemistry 43: 1255-1260.
3. Alexander SP, Mathie A, Peters JA, (2011). Guide to Receptors and Channels (GRAC), 5th edition. Br J Pharmacol 164: S1-S324.
4. Anavi-Goffer S, Baillie G, Irving AJ, Gertsch J, Greig IR, Pertwee RG, et al,. (2011). Modulation of L-α-lysophosphatidylinositol/GPR55 MAP kinase signalling by cannabinoids. J Biol Chem 287: 91-104.
5. Baur R, Gertsch J, Sigel E, (2011). The cannabinoid receptor CB1 antagonists rimonabant (SR141716) and AM251 directly potentiate GABA(A) receptors. Br J Pharmacol 165: 2479-2484.
6. Bisogno T, Di Marzo V, (2010). Cannabinoid receptors and endocannabinoids: role in neuroinflammatory and neurodegenerative disorders. CNS Neurol Disord Drug Targets 5: 564-573.
7. Björklund E, Noren E, Nilsson J, Fowler CJ, (2010). Inhibition of monoacylglycerol lipase by troglitazone, N-arachidonoyldopamine and the irreversible inhibitor JZL184: comparison of two different assays. Br J Pharmacol 161: 1512-1526.
8. Blankman JL, Simon GM, Cravatt BF, (2007). A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem Biol 14: 1347-1356.
9. Breivogel C, (2006). Cannabinoid receptor binding to membrane homogenates and cannabinoid-stimulated [35S]GTP-S binding to membrane homogenates or intact cultured cells. Marijuana and cannabinoid research. Methods Mol Med 123: 149-162.
10. Chianese G, Fattorusso E, Taglialatela-Scafati O, Bavestrello G, Calcinai B, Dien HA, et al,. (2011). Desulfohaplosamate, a new phosphate-containing steroid from Dasychalina sp., is a selective cannabinoid CB2 receptor ligand. Steroids 76: 998-1002.
11. Chicca A, Raduner S, Pellati F, Strompen T, Altmann KH, Schoop R, et al,. (2009). Synergistic immunomopharmacological effects of N-alkylamides in Echinacea purpurea herbal extracts. Int Immunopharmacol 9: 850-858.
12. Ching J, Lin HS, Tan CH, Koh HL, (2011). Quantification of α- and β-amyrin in rat plasma by gas chromatography-mass spectrometry: application to preclinical pharmacokinetic study. J Mass Spectrom 46: 457-464.
13. Da Silva KA, Paszcuk AF, Passos GF, Silva ES, Bento AF, Meotti FC, et al,. (2011). Activation of cannabinoid receptors by the pentacyclic triterpene α,β-amyrin inhibits inflammatory and neuropathic persistent pain in mice. Pain 152: 1872-1287.
14. Dutra RR, Silva KB, Bento AF, Paszcuk AF, Marcon R, Meiotti FC, et al,. (2011). Euphol, a novel cannabinoid agonist, prevents inflammatory and neuropathic persistent pain in rodents. Planta Med 77: 1254.
15. Folch J, Lees M, Sloane Stanley GH, (1957). A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226: 497-509.
16. Fowler CJ, Ghafouri N, (2008). Does the hydrolysis of 2-arachidonoylglycerol regulate its cellular uptake? Pharmacol Res 58: 72-76.
17. Fride E, Perchuk A, Hall FS, Uhl GR, Onaivi ES, (2006). Behavioural methods in cannabinoid research. Methods Mol Med 123: 269-290.
18. Gertsch J, (2011). Botanical drugs, synergy, and network pharmacology: forth and back to intelligent mixtures. Planta Med 77: 1086-1098.
19. Gertsch J, Raduner S, Altmann KH, (2006). New natural noncannabinoid ligands for cannabinoid type-2 (CB2) receptors. J Recept Signal Transduct Res 26: 709-730.
20. Gertsch J, Leonti M, Raduner S, Racz I, Chen JZ, Xie XQ, et al,. (2008). A. Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci USA 105: 9099-90104.
21. Gertsch J, Pertwee RG, Di Marzo V, (2010). Phytocannabinoids beyond the Cannabis plant-do they exist? Br J Pharmacol 160: 523-529.
22. Griffith DA, Hadcock JR, Black SC, Iredale PA, Carpino PA, DaSilva-Jardine P, et al,. (2009). Discovery of 1-[9-(4-chlorophenyl)-8-(2- chlorophenyl)-9H-purin-6-yl]-4-ethylaminopiperidine-4-carboxylic acid amide hydrochloride (CP-945,598), a novel, potent, and selective cannabinoid type 1 receptor antagonist. J Med Chem 52: 234-237.
23. Guindon J, Hohmann AG, (2008). Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain. Br J Pharmacol 153: 319-334.
24. Hadcock JR, Carpino PA, Iredale PA, Dow RL, Gautreau D, Thiede L, et al,. (2010). Quantitative in vitro and in vivo pharmacological profile of CE-178253, a potent and selective cannabinoid type 1 (CB1) receptor antagonist. BMC Pharmacol 10: 9.
25. Holanda Pinto SA, Pinto LM, Guedes MA, Cunha GM, Chaves MH, Santos FA, et al,. (2008). Antinoceptive effect of triterpenoid alpha,beta-amyrin in rats on orofacial pain induced by formalin and capsaicin. Phytomedicine 15: 630-634.
26. Hoover HS, Blankman JL, Niessen S, Cravatt BF, (2008). Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling. Bioorg Med Chem Lett 18: 5838-5841.
27. Huffman JW, Zengin G, Wu M, Lu J, Hynd G, Bushell K, et al,. (2005). Structure-activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB(1) and CB(2) receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB(2) receptor agonists. Bioorg Med Chem 13: 89-112.
28. King AR, Duranti A, Tontini A, Rivara S, Rosengarth A, Clapper JR, et al,. (2007). URB602 inhibits monoacylglycerol lipase and selectively blocks 2-arachidonoylglycerol degradation in intact brain slices. Chem Biol 14: 1357-1365.
29. King AR, Dotsey EY, Lodola A, Jung KM, Ghomian A, Qiu Y, et al,. (2009a). Discovery of potent and reversible monoacylglycerol lipase inhibitors. Chem Biol 16: 1045-1052.
30. King AR, Lodola A, Carmi C, Fu J, Mor M, Piomelli D, (2009b). A critical cysteine residue in monoacylglycerol lipase is targeted by a new class of isothiazolinone-based enzyme inhibitors. Br J Pharmacol 157: 974-983.
31. Labar G, Bauvois C, Borel F, Ferrer JL, Wouters J, Lambert DM, (2010). Crystal structure of the human monoacylglycerol lipase, a key factor in endocannabinoid signaling. Chembiochem 11: 218-227.
32. Leonti M, Casu L, Raduner S, Cottiglia F, Floris C, Altmann KH, et al,. (2010). Falcarinol is a covalent cannabinoid CB1 receptor antagonist and induces pro-allergic effects in skin. Biochem Pharmacol 79: 1815-1826.
33. Lichtman AH, Blankman JL, Cravatt BF, (2010). Endocannabinoid overload. Mol Pharmacol 78: 993-995.
34. Long JZ, Li W, Booker L, Burston JJ, Kinsey SG, Schlosburg JE, et al,. (2009). Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol 5: 37-44.
35. McPartland JM, Glass M, Pertwee RG, (2007). Meta-analysis of cannabinoid ligand binding affinity and receptor distribution: interspecies differences. Br J Pharmacol 152: 583-593.
36. Marazzi J, Kleyer J, Paredes JM, Gertsch J, (2011). Endocannabinoid content in fetal bovine sera-unexpected effects on mononuclear cells and osteoclastogenesis. J Immunol Methods 373: 219-228.
37. Marrs WR, Blankman JL, Horne EA, Thomazeau A, Lin YH, Coy J, et al,. (2010). The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors. Nat Neurosci 13: 951-957.
38. Melo CM, Carvalho KM, Neves JC, Morais TC, Rao VS, Santos FA, et al,. (2010). Alpha,beta-amyrin, a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in rats. World J Gastroenterol 16: 4272-4280.
39. Melo CM, Morais TC, Tomé AR, Brito GA, Chaves MH, Rao VS, et al,. (2011). Anti-inflammatory effect of α,β-amyrin, a triterpene from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice. Inflamm Res 60: 673-681.
40. Noe SN, Newton C, Widen R, Friedman H, Klein TW, (2001). Modulation of CB1 mRNA upon activation of murine splenocytes. Adv Exp Med Bio l493: 215-221.
41. Obata T, Sakurai Y, Kase Y, Tanifuji Y, Horiguchi T, (2003). Simultaneous determination of endocannabinoids (arachidonylethanolamide and 2-arachidonylglycerol) and isoprostane (8-epiprostaglandin F2alpha) by gas chromatography-mass spectrometry-selected ion monitoring for medical samples. J Chromatogr B Analyt Technol Biomed Life Sci 792: 131-140.
42. Onaivi ES, (2011). Commentary: functional Neuronal CB2 Cannabinoid Receptors in the CNS. Curr Neuropharmacol 9: 205-208.
43. Pacher P, Bátkai S, Kunos G, (2006). The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58: 389-462.
44. Papahatjis DP, Kourouli T, Abadji V, Goutopoulos A, Makriyannis A, (1998). Pharmacophoric requirements for cannabinoid side chains: multiple bond and C1'-substituted delta 8-tetrahydrocannabinols. J Med Chem 41: 1195-1200.
45. Pertwee RG, (2009). Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol 156: 397-411.
46. Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, et al,. (2010). International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev 62: 588-631.
47. Raduner S, Majewska A, Chen JZ, Xie XQ, Hamon J, Faller B, et al,. (2006). Alkylamides from Echinacea are a new class of cannabinomimetics. Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects. J Biol Chem 281: 14192-14206.
48. Rees HH, Britton G, Goodwin TW, (1968). The biosynthesis of beta-amyrin. Mechanism of squalene cyclization. Biochem J 106: 659-665.
49. Ríos JL, (2010). Effects of triterpenes on the immune system. J Ethnopharmacol 128: 1-14.
50. Sugiura T, Yoshinaga N, Waku K, (2001). Rapid generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in rat brain after decapitation. Neurosci Lett 297: 175-118.
51. Thakur GA, Palmer SL, Harrington PE, Stergiades IA, Tius MA, Makriyannis A, (2002). Enantiomeric resolution of a novel chiral cannabinoid receptor ligand. J Biochem Biophys Methods 54: 415-422.