ABSTRACT
BACKGROUND: Annona crassiflora Mart., popularly known as "Araticum", is a native tree of the Brazilian Cerrado used in folk medicine for treatment of pain and inflammatory diseases. We proposed to analyze analgesic and anti-inflammatory properties of the filtrate (F1) and the precipitate (F2) of the hydroalcoholic fraction from the leaves of Annona crassiflora Mart. in mice. MATERIALS AND METHODS: Swiss mice were submitted to formalin-induced nociception test and tail-flick reflex test, to assess antinociceptive properties, and to the rota-rod test, for motor performance analyses. To evaluate anti-inflammatory properties, F1 and F2 were orally administered 1 h prior to the intrathoracic injection of carrageenan, zymosan, LPS, CXCL8, or vehicle in Balb/c mice and neutrophil infiltration was evaluated 4 h after injection. RESULTS: F1 and F2 reduced the licking time in the second phase of formalin-induced nociception test, but only F2 showed a dose-dependent response. Neither F1 nor F2 reduced the latency time in the tail-flick reflex test. In addition, motor performance alteration was not observed in F1- or F2-treated mice. F2 treatment significantly inhibited the neutrophilia induced by carrageenan, LPS, or CXCL8, but not zymosan. CONCLUSIONS: The experimental data demonstrated that hydroalcoholic fractions of Annona crassiflora Mart. leaves have remarkable anti-inflammatory and antinociceptive activities.
Subject(s)
Analgesics/pharmacology , Annona/chemistry , Anti-Inflammatory Agents/pharmacology , Pain Measurement/drug effects , Plant Extracts/pharmacology , Plant Leaves/chemistry , Animals , Carrageenan/pharmacology , Disease Models, Animal , Mice , Mice, Inbred BALB CABSTRACT
Peltatoside is a natural compound isolated from leaves of Annona crassiflora Mart., 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-CB1 cannabinoid 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 CB1 cannabinoid antagonist AM251 (160 µg/paw), but not by CB2 cannabinoid 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 CB1 receptors, involving endocannabinoids in this process.
Subject(s)
Analgesics/pharmacology , Cannabinoids/metabolism , Glycosides/pharmacology , Quercetin/analogs & derivatives , Amidohydrolases/metabolism , Analgesics/chemistry , Analgesics/isolation & purification , Animals , Annona/chemistry , Benzodioxoles/administration & dosage , Benzodioxoles/pharmacology , Cannabinoid Receptor Antagonists/pharmacology , Carrageenan/antagonists & inhibitors , Carrageenan/pharmacology , Dose-Response Relationship, Drug , Endocannabinoids/metabolism , Glycosides/antagonists & inhibitors , Glycosides/chemistry , Glycosides/isolation & purification , Hyperalgesia/drug therapy , Male , Mice , Monoacylglycerol Lipases/drug effects , Pain Measurement/drug effects , Piperidines/administration & dosage , Piperidines/pharmacology , Plant Extracts/pharmacology , Pyrazoles/pharmacology , Quercetin/antagonists & inhibitors , Quercetin/chemistry , Quercetin/isolation & purification , Quercetin/pharmacology , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Receptor, Cannabinoid, CB1/metabolism , Receptor, Cannabinoid, CB2/antagonists & inhibitors , Receptor, Cannabinoid, CB2/metabolismABSTRACT
Annona crassiflora, a native tree from Brazilian Cerrado, is reported to possess several ethnomedical uses. Here, we report the isolation and unambiguous characterisation of the flavonoids quercetin-3-O-ß-D-glucopyranosil(1 â 6)-O-α-L-arabinoside (1), known as peltatoside, kaempferol-3-O-ß-D-galactopyranoside (2), quercetin-3-O-ß-D-galactopyranoside (3), quercetin-3-O-ß-L-arabinopiranoside (4) and the ( - )-epicatechin (5) from the hydroalcoholic portion of the leaf ethanolic extract. Their structures were elucidated by using 1D and 2D NMR, ESI-MS, UV/Vis spectroscopy, optical rotation analysis and literature data comparison. The leaf ethanolic extract and its isolated compounds were evaluated by using antimicrobial, antioxidant and larvicidal assays, expressing antimicrobial and antioxidant activities. This is the first report on flavonoid isolation from A. crassiflora.
