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Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity

Marina Klawitter18, Lilian Quero1, Juergen Klasen2, Alexia N Gloess3, Babette Klopprogge3, Oliver Hausmann4, Norbert Boos125 and Karin Wuertz15679*

  • * Corresponding author: Karin Wuertz kwuertz@ethz.ch

  • † Equal contributors

Author Affiliations

1 Spine Research Group, Competence Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland

2 University Hospital Balgrist, University of Zurich, Zurich, Switzerland

3 Institute of Chemistry and Biological Chemistry, Zurich University of Applied Sciences, Waedenswil, Switzerland

4 Department of Neurosurgery, Clinic St. Anna, Lucerne, Switzerland

5 AOSpine Research Network, Duebendorf, Switzerland

6 Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland

7 Institute for Biomechanics, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland

8 Bone and Stem Cell Research Group, Competence Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland

9 Institute for Biomechanics, Swiss Federal Institute of Technology (ETH) Zurich, Schafmattstrasse 30, 8093, Zurich, Switzerland

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Journal of Inflammation 2012, 9:29  doi:10.1186/1476-9255-9-29

Published: 21 August 2012

Abstract

Background

As proinflammatory cytokines seem to play a role in discogenic back pain, substances exhibiting anti-inflammatory effects on intervertebral disc cells may be used as minimal-invasive therapeutics for intradiscal/epidural injection. The purpose of this study was to investigate the anti-inflammatory and anti-catabolic potential of curcuma, which has been used in the Indian Ayurvedic medicine to treat multiple ailments for a long time.

Methods

Human disc cells were treated with IL-1β to induce an inflammatory/catabolic cascade. Different extracts of curcuma as well as curcumin (= a component selected based on results with curcuma extracts and HPLC/MS analysis) were tested for their ability to reduce mRNA expression of proinflammatory cytokines and matrix degrading enzymes after 6 hours (real-time RT-PCR), followed by analysis of typical inflammatory signaling mechanisms such as NF-κB (Western Blot, Transcription Factor Assay), MAP kinases (Western Blot) and Toll-like receptors (real-time RT-PCR). Quantitative data was statistically analyzed using a Mann Whitney U test with a significance level of p < 0.05 (two-tailed).

Results

Results indicate that the curcuma DMSO extract significantly reduced levels of IL-6, MMP1, MMP3 and MMP13. The DMSO-soluble component curcumin, whose occurrence within the DMSO extract was verified by HPLC/MS, reduced levels of IL-1β, IL-6, IL-8, MMP1, MMP3 and MMP13 and both caused an up-regulation of TNF-α. Pathway analysis indicated that curcumin did not show involvement of NF-κB, but down-regulated TLR2 expression and inhibited the MAP kinase JNK while activating p38 and ERK.

Conclusions

Based on its anti-inflammatory and anti-catabolic effects, intradiscal injection of curcumin may be an attractive treatment alternative. However, whether the anti-inflammatory properties in vitro lead to analgesia in vivo will need to be confirmed in an appropriate animal model.

Keywords:
Human intervertebral disc cells; Curcumin; Curcuma; Proinflammatory cytokines; Matrix degrading enzymes; NF-κB; Toll-like receptors; MAP kinase; Back pain; HPLC/MS