Abstract |
7-Hydroxycoumarin ( umbelliferone, 1), the main metabolite of coumarin, has been reported to produce potent antinociceptive effects in animal models of pain. However, the biochemical events involved in antinociception mediated by 1 are currently not well understood. In the present study, the mechanisms by which 1 exerts its pharmacological actions were investigated. Acute pretreatment of mice with 1 produced a long-lasting antinociceptive effect against complete Freund's adjuvant (CFA)-induced hyperalgesia. The subchronic administration of 1 inhibited CFA-induced hyperalgesia and paw edema, while it did not cause any apparent toxicity. Another set of experiments showed that 1 inhibited carrageenan-induced mechanical hyperalgesia, but not mechanical hyperalgesia induced by prostaglandin E(2) ( PGE(2)), suggesting that it acts upstream of PGE(2.) Treatment with 1 was able to prevent the plantar tissue neutrophil influx induced by local inflammatory stimuli. In addition, 1 exhibited inhibitory effects on the release of hyperalgesic cytokines (TNF-α and IL-1β) and the production of PGE(2), a directly acting hyperalgesic mediator. The present results suggest that the antinociceptive effect of 1 is correlated with the inhibition of neutrophil migration, cytokine release, and PGE(2) production and are supportive of the further investigation of the therapeutic potential of 1 to control inflammatory pain.
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Authors | Flávia Oliveira de Lima, Fabiana Regina Nonato, Ricardo David Couto, José Maria Barbosa Filho, Xirley Pereira Nunes, Ricardo Ribeiro dos Santos, Milena Botelho Pereira Soares, Cristiane Flora Villarreal |
Journal | Journal of natural products
(J Nat Prod)
Vol. 74
Issue 4
Pg. 596-602
(Apr 25 2011)
ISSN: 1520-6025 [Electronic] United States |
PMID | 21417376
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics
- Tumor Necrosis Factor-alpha
- Umbelliferones
- 7-hydroxycoumarin
- Freund's Adjuvant
- Dinoprostone
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Topics |
- Analgesics
(chemistry, metabolism, pharmacology, therapeutic use)
- Animals
- Brazil
- Dinoprostone
(pharmacology)
- Edema
(chemically induced, drug therapy)
- Freund's Adjuvant
(pharmacology)
- Mice
- Models, Animal
- Molecular Structure
- Neutrophils
(drug effects, physiology)
- Pain
(chemically induced, drug therapy)
- Pain Measurement
- Tumor Necrosis Factor-alpha
(pharmacology)
- Umbelliferones
(chemistry, pharmacology, therapeutic use)
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