These authors contributed equally to this work.
6-Shogaol inhibits chondrocytes’ innate immune responses and cathepsin-K activity
Article first published online: 30 AUG 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 2, pages 256–266, February 2014
How to Cite
Villalvilla, A., da Silva, J. A., Largo, R., Gualillo, O., Vieira, P. C., Herrero-Beaumont, G. and Gómez, R. (2014), 6-Shogaol inhibits chondrocytes’ innate immune responses and cathepsin-K activity. Mol. Nutr. Food Res., 58: 256–266. doi: 10.1002/mnfr.201200833
- Issue published online: 3 FEB 2014
- Article first published online: 30 AUG 2013
- Manuscript Accepted: 30 JUN 2013
- Manuscript Revised: 8 JUN 2013
- Manuscript Received: 17 DEC 2012
- CAPES, CNPq, and FAPESP
Ginger has long been used in traditional Asian medicine to treat osteoarthritis. Indeed, scientific research has reported that ginger derivatives (GDs) have the potential to control innate immune responses. Given the widespread use and demonstrated properties of GDs, we set out to study their anti-inflammatory and anticatabolic properties in chondrocytes.
Methods and results
6-shogaol (6-S), the most active GD, was obtained from ginger. 6-S was not toxic as measured by MTT assay, and inhibited NO production and IL-6 and MCP-1 induced gene expression in LPSbut not in IL-1β-stimulated chondrocytes. 6-S also inhibited LPS-mediated ERK1/2 activation as well as NOS2 and MyD88 induced expression as determined by Western blot. Moreover, zymography revealed that 6-S inhibited matrix metalloproteinases (MMP) 2/9 induction in LPS-treated cells. Hydrated 6-S was modified to obtain a compound (SSi6) without 6-S potential anti-inflammatory properties. Both 6-S and SSi6 inhibited cathepsin-K activity.
6-S blocked TLR4-mediated innate immune responses and MMP induction in chondrocytes. These results, together with GDs-mediated cathepsin-K inhibition, suggest the potential for GDs use against cartilage and bone degradation. Therefore, considering that clinical trials involving oral administration of ginger achieved relevant nontoxic GDs serum concentrations, we suggest that a ginger-supplemented diet might reduce OA symptoms.