Mechanisms Involved in the Antinociceptive Effects of 7-Hydroxycoumarin

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• 作者：Fla虂via Oliveira de Lima ; Fabiana Regina Nonato ; Ricardo David Couto ; Jose虂 Maria Barbosa Filho ; Xirley Pereira Nunes ; Ricardo Ribeiro dos Santos ; Milena Botelho Pereira Soares ; Cristiane Flora Villarreal
• 刊名：Journal of Natural Products
• 出版年：2011
• 出版时间：April 25, 2011
• 年：2011
• 卷：74
• 期：4
• 页码：596-602
• 全文大小：853K
• 年卷期：v.74,no.4(April 25, 2011)
• ISSN：1520-6025

文摘

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鈥檚 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 E₂ (PGE₂), 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-伪 and IL-1尾) and the production of PGE₂, 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 PGE₂ production and are supportive of the further investigation of the therapeutic potential of 1 to control inflammatory pain.