Pimaradienoic Acid Inhibits Inflammatory Pain: Inhibition of NF-魏B Activation and Cytokine Production and Activation of the NO鈥揅yclic GMP鈥揚rotein Kinase G鈥揂TP-Sensitive Potassium Channel Signaling Pat

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• 作者：Maria I. Possebon ; Sandra S. Mizokami ; Thacyana T. Carvalho ; Ana C. Zarpelon ; Miriam S. N. Hohmann ; Larissa Staurengo-Ferrari ; Camila R. Ferraz ; Thiago H. Hayashida ; Anderson R. de Souza ; Sergio R. Ambrosio ; Nilton S. Arakawa ; Rubia Casagrande ; Waldiceu A. Verri ; Jr.
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：November 26, 2014
• 年：2014
• 卷：77
• 期：11
• 页码：2488-2496
• 全文大小：421K
• ISSN：1520-6025

文摘

Pimaradienoic acid (1) is a pimarane diterpene (ent-pimara-8(14),15-dien-19-oic acid) extracted at high amounts from various plants including Vigueira arenaria Baker. Compound 1 inhibited carrageenan-induced paw edema and acetic acid-induced abdominal writhing, which are its only known anti-inflammatory activities. Therefore, it is important to further investigate the analgesic effects of 1. Oral administration of 1 (1, 3, and 10 mg/kg) inhibited the acetic acid-induced writhing. This was also observed at 10 mg/kg via sc and ip routes. Both phases of the formalin- and complete Freund鈥檚 adjuvant (CFA)-induced paw flinch and time spent licking the paw were inhibited by 1. Compound 1 inhibited carrageenan-, CFA-, and PGE₂-induced mechanical hyperalgesia. Treatment with 1 inhibited carrageenan-induced production of TNF-伪, IL-1尾, IL-33, and IL-10 and nuclear factor 魏B activation. Pharmacological inhibitors also demonstrated that the analgesic effects of 1 depend on activation of the NO鈥揷yclic GMP鈥損rotein kinase G鈥揂TP-sensitive potassium channel signaling pathway. Compound 1 did not alter plasma levels of AST, ALT, or myeloperoxidase activity in the stomach. These results demonstrate that 1 causes analgesic effects associated with the inhibition of NF-魏B activation, reduction 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.