Kaurenoic Acid from Sphagneticola trilobata Inhibits Inflammatory Pain: Effect on Cytokine Production and Activation of the NO–Cyclic GMP–Protein Kinase G–ATP-Sensitive Potassium Channel Signaling Pathway
| Autor: | Ana C. Zarpelon, Rubia Casagrande, Sérgio Ricardo Ambrósio, Sergio H. Ferreira, Fernando Q. Cunha, Nilton S. Arakawa, Sandra S. Mizokami, Thiago M. Cunha, Waldiceu A. Verri |
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| Rok vydání: | 2012 |
| Předmět: |
ATP-sensitive potassium channel
medicine.medical_treatment Freund's Adjuvant Carbazoles Administration Oral Pain Pharmaceutical Science Asteraceae Pharmacology Analytical Chemistry Mice Acetic acid chemistry.chemical_compound KATP Channels Formaldehyde Glyburide Drug Discovery Cyclic GMP-Dependent Protein Kinases medicine Animals DOR Acetic Acid Inflammation Dose-Response Relationship Drug Molecular Structure Tumor Necrosis Factor-alpha Kinase Interleukin-8 Organic Chemistry Potassium channel NG-Nitroarginine Methyl Ester Cytokine Nociception Complementary and alternative medicine chemistry Cytokines Molecular Medicine Diterpenes Signal transduction cGMP-dependent protein kinase Injections Intraperitoneal |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/np200989t |
| Popis: | 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's adjuvant (CFA), and both phases of the formalin test. Compound 1 also inhibited acute carrageenin- and PGE(2)-induced and chronic CFA-induced inflammatory mechanical hyperalgesia. Mechanistically, 1 inhibited the production of the hyperalgesic cytokines TNF-α and IL-1β. Furthermore, the analgesic effect of 1 was inhibited by l-NAME, ODQ, KT5823, and glybenclamide treatment, demonstrating that such activity also depends on activation of the NO-cyclic GMP-protein kinase G-ATP-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-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway. |
| Databáze: | OpenAIRE |
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