Abstract
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.
Key words
Annonaceae -
Annona crassiflora
- Quercetin - peltatoside - cannabinoid - peripheral antinociception
