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.
