title: Tanshinone IIA represses inflammatory response and reduces radiculopathic pain by inhibiting IRAK-1 and NF-κB/p38/JNK signaling.
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.
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, 324# JingWuWeiQi Road, Jinan 250021, Shandong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Operation, Shandong University QiLu Hospital, Shandong University, 106# Wenhua West Road,Jinan 250012, Shandong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical Department, Shandong Provincial Hospital Affiliated to Shandong University, 324# JingWuWeiQi Road, Jinan 250021, Shandong, China.
authors.forename: Cuiyan
authors.initials: C
authors.lastname: Xing
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, 324# JingWuWeiQi Road, Jinan 250021, Shandong, China. Electronic address: zhangmy717@163.com.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Zhang
mesh_terms: D045784:Abietanes / Q000494:pharmacology / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D053583:Interleukin-1beta; D007403:Intervertebral Disc / Q000166:cytology; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy*; D007405:Intervertebral Disc Displacement / Q000188:drug therapy*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010146:Pain / Q000188:drug therapy*; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D045784:Abietanes; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D016328:NF-kappa B; C021751:tanshinone; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: IRAK-1; Inflammatory response; Intervertebral disc; NF-κB; Radiculopathy; Tanshinone IIA