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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

Mizokami, Sandra S.; Arakawa, Nilton S.; Ambrosio, Sergio R.; Zarpelon, Ana C.; Casagrande, Rubia; Cunha, Thiago M.; Ferreira, Sergio H.; Cunha, Fernando Q.; Verri, Waldiceu A., Jr. Universidade De São Paulo

JOURNAL OF NATURAL PRODUCTS, WASHINGTON, v. 75, n. 5, supl. 1, Part 3, pp. 896-904, MAY, 2012

AMER CHEMICAL SOC; WASHINGTON 2013-08-02

Acesso online

  • Título:
    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: Mizokami, Sandra S.; Arakawa, Nilton S.; Ambrosio, Sergio R.; Zarpelon, Ana C.; Casagrande, Rubia; Cunha, Thiago M.; Ferreira, Sergio H.; Cunha, Fernando Q.; Verri, Waldiceu A., Jr.
  • Universidade De São Paulo
  • Assuntos: Aralia-Continentalis; Mechanical Hypernociception; Antiinflammatory Activity; Neutrophil Migration; Wedelia-Paludosa; Etb Receptors; Mice; Rats; Nociception; Constituents; Plant Sciences; Chemistry; Medicinal; Pharmacology & Pharmacy
  • É parte de: JOURNAL OF NATURAL PRODUCTS, WASHINGTON, v. 75, n. 5, supl. 1, Part 3, pp. 896-904, MAY, 2012
  • Descrição: 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-alpha and IL-1 beta. 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 lcinase G-ATP-sensitive potassium channel signaling pathway.
    Fundacao de Amparo a Pesquisa do Estado de So Paulo (FAPESP, Brazil)
    Conselho Nacional de Pesquisa (CNPq, Brazil)
    Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil
    Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil)
    Fundacao Araucaria and Governo do Estado do Parana (Brazil)
  • DOI: 10.1021/np200989t
  • Títulos relacionados: JOURNAL OF NATURAL PRODUCTS
  • Editor: AMER CHEMICAL SOC; WASHINGTON
  • Data de publicação: 2013-08-02
  • Idioma: Inglês

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