Tanshinone IIA represses inflammatory response and reduces radiculopathic pain by inhibiting IRAK-1 and NF-κB/p38/JNK signaling

Int Immunopharmacol. 2015 Sep;28(1):382-9. doi: 10.1016/j.intimp.2015.06.032. Epub 2015 Jul 7.

Abstract

Intervertebral disc (IVD) disease, a most common cause of disc failure and low back pain, is characterized by age-related changes in the adult disc. In this study we aimed to investigate the potential of Tanshinone IIA (TSA) for the treatment of IVD disease, through exploring its anti-inflammatory and anti-catabolic activities in both in vitro IVD cell culture and in vivo animal models. After the inflammatory response was induced in IVD cells by IL-1β, the activity and expression of inflammatory mediators, and potentially involved pathways were investigated in the presence or absence of TSA. The p38-MAPK inhibitor, SB239063, was also used to investigate the involvement of the MAPK signaling pathway in the observed effects. Meanwhile, the analgesic properties of TSA were analyzed by the von Frey filament test in Sprague-Dawley rats. Our results indicated that TSA significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, probably by modulation of the activity of interleukin-1 receptor-associated kinase 1 (IRAK-1) and its downstream effectors p38, JNK and NF-κB. Our current study strongly demonstrates the potential of TSA for the treatment of inflammation and followed pain in degenerative disc disease.

Keywords: IRAK-1; Inflammatory response; Intervertebral disc; NF-κB; Radiculopathy; Tanshinone IIA.

MeSH terms

  • Abietanes* / pharmacology
  • Abietanes* / therapeutic use
  • Analgesics* / pharmacology
  • Analgesics* / therapeutic use
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal* / therapeutic use
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Drugs, Chinese Herbal* / pharmacology
  • Drugs, Chinese Herbal* / therapeutic use
  • Female
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Interleukin-1beta
  • Intervertebral Disc / cytology
  • Intervertebral Disc Degeneration / drug therapy*
  • Intervertebral Disc Displacement / drug therapy*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Pain / drug therapy*
  • Rats, Sprague-Dawley
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Abietanes
  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Drugs, Chinese Herbal
  • Interleukin-1beta
  • NF-kappa B
  • tanshinone
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Interleukin-1 Receptor-Associated Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • MMP1 protein, human
  • Matrix Metalloproteinase 1

Supplementary concepts

  • Intervertebral disc disease