Kaurenoic Acid from Sphagneticola trilobata Inhibits Inflammatory Pain: Effect on Cytokine Production and Activation of the NO鈥揅yclic GMP鈥揚rotein Kinase G鈥揂TP-Sensitive Potassium Channel Signal

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• 作者：Sandra S. Mizokami ; Nilton S. Arakawa ; Sergio R. Ambrosio ; Ana C. Zarpelon ; Rubia Casagrande ; Thiago M. Cunha ; Sergio H. Ferreira ; Fernando Q. Cunha ; Waldiceu A. Verri ; Jr.
• 刊名：Journal of Natural Products
• 出版年：2012
• 出版时间：May 25, 2012
• 年：2012
• 卷：75
• 期：5
• 页码：896-904
• 全文大小：464K
• 年卷期：v.75,no.5(May 25, 2012)
• ISSN：1520-6025

文摘

Kaurenoic acid [ent-kaur-16-en-19-oic acid (1)] is a diterpene present in several plants including Sphagneticola trilobata. The only documented evidence for its antinociceptive effect is that it inhibits the writhing response induced by acetic acid in mice. Therefore, the analgesic effect of 1 in different models of pain and its mechanisms in mice were investigated further. Intraperitoneal and oral treatment with 1 dose-dependently inhibited inflammatory nociception induced by acetic acid. Oral treatment with 1 also inhibited overt nociception-like behavior induced by phenyl-p-benzoquinone, complete Freund鈥檚 adjuvant (CFA), and both phases of the formalin test. Compound 1 also inhibited acute carrageenin- and PGE<sub>2sub>-induced and chronic CFA-induced inflammatory mechanical hyperalgesia. Mechanistically, 1 inhibited the production of the hyperalgesic cytokines TNF-伪 and IL-1尾. Furthermore, the analgesic effect of 1 was inhibited by <span class="smallcaps">lspan>-NAME, ODQ, KT5823, and glybenclamide treatment, demonstrating that such activity also depends on activation of the NO鈥揷yclic GMP鈥損rotein kinase G鈥揂TP-sensitive potassium channel signaling pathway, respectively. These results demonstrate that 1 exhibits an analgesic effect in a consistent manner and that its mechanisms involve the inhibition of cytokine production and activation of the NO鈥揷yclic GMP鈥損rotein kinase G鈥揂TP-sensitive potassium channel signaling pathway.