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Inflammopharmacology. 2018 Feb;26(1):227-233. doi: 10.1007/s10787-017-0391-7. Epub 2017 Sep 9.

Tingenone, a pentacyclic triterpene, induces peripheral antinociception due to cannabinoid receptors activation in mice.

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Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas (UFAM), Av. General Rodrigo Octávio Jordão Ramos, 3000, Coroado I, Manaus, AM, 69.077-000, Brazil.
Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
Department of Chemistry, Institute of Exact Sciences, UFMG, Belo Horizonte, MG, Brazil.


Several works have shown that triterpenes induce peripheral antinociception by activation of cannabinoid receptors and endocannabinoids; besides, several research groups have reported activation of cannabinoid receptors in peripheral antinociception. The aim of this study was to assess the involvement of the cannabinoid system in the antinociceptive effect induced by tingenone against hyperalgesia evoked by prostaglandin E2 (PGE2) at peripheral level. The paw pressure test was used and the hyperalgesia was induced by intraplantar injection of PGE2 (2 μg/paw). All drugs were injected subcutaneously in the hind paws of male Swiss mice. Tingenone (200 µg/paw) administered into the right hind paw induced a local antinociceptive effect, that was antagonized by AM630, a selective antagonist to CB2 cannabinoid receptor. AM251, a selective antagonist to CB1 cannabinoid receptor, did not alter the peripheral antinociceptive effect of tingenone. MAFP, a fatty acid amide hydrolase (FAAH) inhibitor; VDM11, an anandamide reuptake inhibitor; and JZL184, monoacylglycerol lipase (MAGL) inhibitor did not potentiate the peripheral antinociceptive effect of the lower dose of tingenone (50 µg/paw). The results suggest that tingenone induced a peripheral antinociceptive effect via cannabinoid receptor activation. Therefore, this study suggests a pharmacological potential for a new analgesic drug.


Cannabinoid receptors; Pentacyclic triterpene; Peripheral antinociception; Tingenone

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