Dehydroabietic Acid Suppresses Inflammatory Response Via Suppression of Src-, Syk-, and TAK1-Mediated Pathways

Int J Mol Sci. 2019 Mar 29;20(7):1593. doi: 10.3390/ijms20071593.

Abstract

Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid derived from coniferous plants such as Pinus and Picea. Various bioactive effects of DAA have been studied including antibacterial, antifungal, and anticancer activities. However, the anti-inflammatory mechanism of DAA remains unclear. We evaluated the anti-inflammatory effect of DAA in macrophage cell lines. Dehydroabietic acid clearly reduced nitric oxide (NO) production and inflammatory gene expression decreased according to RT-PCR results. Dehydroabietic acid displayed anti-inflammatory activity at the transcriptional level in results from NF-κB- or AP-1-mediated luciferase assays. To identify the DAA target protein, we investigated NF-κB and AP-1 pathways by Western blotting analysis. Dehydroabietic acid suppressed the activity of proto-oncogene tyrosine protein kinase (Src) and spleen tyrosine kinase (Syk) in the NF-κB cascade and transforming growth factor beta-activated kinase 1 (TAK1) in the AP-1 cascade. Using overexpression strategies, we confirmed that DAA targeted these kinases. Our findings demonstrate the anti-inflammatory effects and molecular mechanism of DAA. This suggests that DAA has potential as a drug or supplement to ameliorate inflammation.

Keywords: AP-1; NF-κB; dehydroabietic acid (DAA); inflammation.

MeSH terms

  • Abietanes / chemistry
  • Abietanes / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cell Death / drug effects
  • Inflammation / pathology*
  • MAP Kinase Kinase Kinases / metabolism*
  • Mice
  • Models, Biological
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • RAW 264.7 Cells
  • Signal Transduction* / drug effects
  • Syk Kinase / metabolism*
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic / drug effects
  • src-Family Kinases / metabolism*

Substances

  • Abietanes
  • Anti-Inflammatory Agents
  • NF-kappa B
  • Transcription Factor AP-1
  • dehydroabietic acid
  • Nitric Oxide
  • Syk Kinase
  • src-Family Kinases
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7