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

Authors

  • Amanda Villalvilla,

    1. Osteoarticular Pathology Lab, IIS-Fundación Jiménez Díaz, Avda Reyes Católicos, Madrid, Spain
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    • These authors contributed equally to this work.

  • Jame's A. da Silva,

    1. Department of Chemistry, Laboratory of Natural Products, Federal University of São Carlos, São Carlos, SP, Brazil
    2. Núcleo de Farmácia, Federal University of Sergipe, Lagarto, SE, Brazil
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    • These authors contributed equally to this work.

  • Raquel Largo,

    1. Osteoarticular Pathology Lab, IIS-Fundación Jiménez Díaz, Avda Reyes Católicos, Madrid, Spain
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  • Oreste Gualillo,

    1. SERGAS, Santiago University Clinical Hospital Research laboratory 9 (NEIRID LAB), Institute of Medical Research (IDIS), Santiago de Compostela, Spain
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  • Paulo Cezar Vieira,

    1. Department of Chemistry, Laboratory of Natural Products, Federal University of São Carlos, São Carlos, SP, Brazil
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  • Gabriel Herrero-Beaumont,

    1. Osteoarticular Pathology Lab, IIS-Fundación Jiménez Díaz, Avda Reyes Católicos, Madrid, Spain
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  • Rodolfo Gómez

    Corresponding author
    1. Osteoarticular Pathology Lab, IIS-Fundación Jiménez Díaz, Avda Reyes Católicos, Madrid, Spain
    • Correspondence: Dr. Rodolfo Gómez Bahamonde, Osteoarticular Pathology Lab, IIS-Fundación Jiménez Díaz. Av. Reyes Católicos 2, 28040 Madrid, Spain

      E-mail: rodolfobahamonde@gmail.com

      Fax: +34-91-544-2636

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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.

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