6‐Shogaol inhibits chondrocytes’ innate immune responses and cathepsin‐K activity

• Published in: Molecular nutrition & food research 2014-02, Vol.58 (2), p.256-266
• Main Authors: Villalvilla, Amanda, Silva, Jame's A, Largo, Raquel, Gualillo, Oreste, Vieira, Paulo Cezar, Herrero‐Beaumont, Gabriel, Gómez, Rodolfo
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; cartilage; Catechols - pharmacology; Cathepsin K - antagonists & inhibitors; Cathepsin K - metabolism; Cell Survival - drug effects; Cells, Cultured; Chemokine CCL2 - metabolism; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; clinical trials; diet; Diseases of the osteoarticular system; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; gelatinase A; gene expression; Ginger; Humans; immune response; Immunity, Innate - drug effects; Inflammation; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Lipopolysaccharides - adverse effects; MAP Kinase Signaling System; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Miscellaneous. Osteoarticular involvement in other diseases; Myeloid Differentiation Factor 88 - metabolism; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; oral administration; Oriental traditional medicine; Osteoarthritis; Osteoarthritis - drug therapy; Osteoarthritis - metabolism; Plant Extracts - pharmacology; TLRs; Toll-Like Receptor 4 - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Western blotting; Zingiber officinale - chemistry
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201200833

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.