Preprint / Version 1

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

Authors

  • Marina Klawitter Spine Research Group, Competence Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland
  • Lilian Quero Spine Research Group, Competence Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland
  • Juergen Klasen University Hospital Balgrist, University of Zurich, Zurich, Switzerland
  • Alexia Gloess Institute of Chemistry and Biological Chemistry, Zurich University of Applied Sciences, Waedenswil, Switzerland
  • Babette Klopprogge Institute of Chemistry and Biological Chemistry, Zurich University of Applied Sciences, Waedenswil, Switzerland
  • Oliver Hausmann Department of Neurosurgery, Clinic St. Anna, Lucerne, Switzerland
  • Norbert Boos Spine Research Group, Competence Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland
  • Karin Wuertz Spine Research Group, Competence Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland

Keywords:

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

Abstract

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

Author Biographies

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

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

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

AOSpine Research Network, Duebendorf, Switzerland

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

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

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