RRC ID 44651
Author Villalvilla A, da Silva JA, Largo R, Gualillo O, Vieira PC, Herrero-Beaumont G, Gómez R.
Title 6-Shogaol inhibits chondrocytes' innate immune responses and cathepsin-K activity.
Journal Mol Nutr Food Res
Abstract SCOPE: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.
CONCLUSION: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.
Volume 58(2)
Pages 256-66
Published 2014-2
DOI 10.1002/mnfr.201200833
PMID 24039109
MeSH Anti-Inflammatory Agents / pharmacology Catechols / pharmacology* Cathepsin K / antagonists & inhibitors Cathepsin K / metabolism* Cell Survival / drug effects Cells, Cultured Chemokine CCL2 / metabolism Chondrocytes / drug effects* Chondrocytes / metabolism Ginger / chemistry Humans Immunity, Innate / drug effects* Interleukin-1beta / metabolism Interleukin-6 / metabolism Lipopolysaccharides / adverse effects MAP Kinase Signaling System Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / metabolism Myeloid Differentiation Factor 88 / metabolism Nitric Oxide / metabolism Nitric Oxide Synthase Type II / metabolism Osteoarthritis / drug therapy Osteoarthritis / metabolism Plant Extracts / pharmacology* Toll-Like Receptor 4 / metabolism
IF 4.653
Times Cited 15
Human and Animal Cells