Article

Duhuo Jisheng Decoction inhibits SDF-1-induced inflammation and matrix degradation in human degenerative nucleus pulposus cells in vitro through the CXCR4/NF-κB pathway

Authors: Zong-chao LIU1, Zhen-long WANG1, Chen-yi HUANG1, Zhi-jiang FU1, Yong LIU1, Zhang-chao WEI1, Shi-gui LIU1, Chuan MA1, Jie-liang SHEN2, Dayue Darrel DUAN3,4
1 Department of Orthopedic Surgery, the Traditional Chinese Medicine Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
2 Department of Orthopedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
3 Center for Phenomics of Traditional Chinese Medicine, Southwest Medical University, Luzhou 646000, China
4 Laboratory of Cardiovascular Phenomics, Department of Pharmacology, University of Nevada Reno School of Medicine, Reno, NV 89557, USA
Corresponding to: Zong-chao LIU: 565409672@qq.com, Chuan MA: langmanzhishen2008@163.com,
DOI: 10.1038/aps.2018.36
Received: 1 September 2017
Accepted: 23 April 2018
Advance online: 24 May 2018

Abstract

Abstract
Lower back pain (LBP) is the most common disease in orthopedic clinics world-wide. A classic Fangji of traditional Chinese medicine, Duhuo Jisheng Decoction (DHJSD), has been proven clinically effective for LBP but its therapeutic mechanisms remain unclear. We hypothesized that DHJSD might relieve LBP through inhibiting the exaggerated proinflammatory cytokines and extracellular matrix (ECM) degradation. Thus, we studied the effects of DHJSD on stromal cell-derived factor-1 (SDF-1)-induced inflammation and ECM degradation in human nucleus pulposus cells (hNPCs). The primary hNPCs were isolated from either degenerated human intervertebral disc (HID) of LBP patients or normal HID of lumbar vertebral fracture patients, and cultured in vitro. The cells were treated with SDF-1 (10 ng/mL) and subsequently with different concentrations (100–500 μg/mL) of DHJSD for 24 h, respectively. We found that application of DHJSD significantly antagonized the SDF-1-induced production of proinflammatory cytokines and reduction of aggrecan and type II collagen in the hNPCs. DHJSD also markedly reduced the SDF-1-induced increase of CXCR4 and p-p65 and inhibited the nuclear translocation of p65 in the hNPCs. DHJSD, CXCR4-siRNA, and NF-κB inhibitor (BAY11-7082) caused the same inhibition of exaggerated proinflammatory cytokines in the SDF-1-treated hNPCs. These results provided compelling evidence that DHJSD may inhibit the generation of proinflammatory mediators and ECM degradation of HID through an orchestrated targeting at multiple molecules in the SDF-1/CXCR4/NF-κB pathway, thus offered novel mechanistic insights into the clinical effectiveness of DHJSD on LBP.
Keywords: duhuojisheng decoction; traditional Chinese medicine; SDF-1; NF-κB; degenerative intervertebral disc; lower back pain