Pimaradienoic acid inhibits inflammatory pain: inhibition of NF-κB activation and cytokine production and activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway.

Abstract

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's 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-α, IL-1β, IL-33, and IL-10 and nuclear factor κB activation. Pharmacological inhibitors also demonstrated that the analgesic effects of 1 depend on activation of the NO-cyclic GMP-protein kinase G-ATP-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-κB activation, reduction of cytokine production, and activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway.

• Authors: 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
• Journal: Journal of natural products (J Nat Prod) Vol. 77 Issue 11 Pg. 2488-96 (Nov 26 2014) ISSN: 1520-6025 [Electronic] United States
• PMID: 25394199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Anti-Inflammatory Agents
• Diterpenes
• Interleukin-1beta
• KATP Channels
• Potassium Channels
• Tumor Necrosis Factor-alpha
• Interleukin-10
• pimaric acid
• Carrageenan
• Freund's Adjuvant
• Cyclic GMP
• Acetic Acid

Topics

• Acetic Acid (pharmacology)
• Analgesics (pharmacology)
• Anti-Inflammatory Agents (pharmacology)
• Carrageenan (pharmacology)
• Cyclic GMP (metabolism)
• Diterpenes (chemistry, pharmacology)
• Edema (chemically induced)
• Freund's Adjuvant (pharmacology)
• Hyperalgesia (drug therapy)
• Interleukin-10 (metabolism)
• Interleukin-1beta (metabolism)
• KATP Channels (drug effects)
• Molecular Structure
• Pain (drug therapy)
• Potassium Channels (drug effects)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (pharmacology)