title: Peltatoside Isolated from Annona crassiflora Induces Peripheral Antinociception by Activation of the Cannabinoid System.
abstract: Peltatoside is a natural compound isolated from leaves ofAnnona crassifloraMart., a plant widely used in folk medicine. This substance is an analogue of quercetin, a flavonoid extensively studied because of its diverse biological activities, including analgesic effects. Besides, a previous study suggested, by computer structure analyses, a possible quercetin-CB1cannabinoid receptor interaction. Thus, the aim of this work was to assess the antinociceptive effect of peltatoside and analyze the cannabinoid system involvement in this action. The mouse paw pressure test was used and hyperalgesia was induced by intraplantar injection of carrageenan (200 µg/paw). All used drugs were administered by intraplantar administration in Swiss male mice (n = 6). Peltatoside (100 µg/paw) elicited a local inhibition of hyperalgesia. The peripheral antinociceptive action of peltatoside was antagonized by the CB1cannabinoid antagonist AM251 (160 µg/paw), but not by CB2cannabinoid antagonist AM630 (100 µg/paw). In order to assess the role of endocannabinoids in this peripheral antinociceptive effect, we used (i) [5Z,8Z,11Z,14Z]-5,8,11,14-eicosatetraenyl-methyl ester phosphonofluoridic acid, an inhibitor of anandamide amidase; (ii) JZL184, an inhibitor for monoacylglycerol lipase, the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol; and (iii) VDM11, an endocannabinoid reuptake inhibitor. MAFP, JZL184, and VDM11 did not induce antinociception, respectively, at the doses 0.5, 3.8, and 2.5 µg/paw, however, these three drugs were able to potentiate the peripheral antinociceptive effect of peltatoside at an intermediary dose (50 µg/paw). Our results suggest that this natural substance is capable of inducing analgesia through the activation of peripheral CB1receptors, involving endocannabinoids in this process.
authors: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors: Cristina da Costa
authors: CD
authors: Oliveira
authors: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors: Clarice de Carvalho
authors: CC
authors: Veloso
authors: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors: Renata Cristina Mendes
authors: RC
authors: Ferreira
authors: Department of Chemistry, Institute of Exact Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil.
authors: Gisele Avelar
authors: GA
authors: Lage
authors: Department of Chemistry, Institute of Exact Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil.
authors: Lúcia Pinheiro Santos
authors: LP
authors: Pimenta
authors: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors: Igor Dimitri Gama
authors: ID
authors: Duarte
authors: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors: Thiago Roberto Lima
authors: TR
authors: Romero
authors: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors: Andrea de Castro
authors: AC
authors: Perez
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000700:Analgesics / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D031041:Annona / Q000737:chemistry; D052117:Benzodioxoles / Q000008:administration & dosage / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002186:Cannabinoids / Q000378:metabolism*; D002351:Carrageenan / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000378:metabolism; D006027:Glycosides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D051379:Mice; D008994:Monoacylglycerol Lipases / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000700:Analgesics; D052117:Benzodioxoles; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D063388:Endocannabinoids; D006027:Glycosides; C534333:JZL 184; D010880:Piperidines; D010936:Plant Extracts; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C000592193:quercetin-3-O-beta-D-glucopyranosil(1-6)-O-alpha-L-arabinoside; C103505:AM 251; D002351:Carrageenan; D011794:Quercetin; D008994:Monoacylglycerol Lipases; D000581:Amidohydrolases; C087226:arachidonoylethanolamide synthase