Backgroundand objectives Ginger has been used in Asiatic traditional medicine, as an arthritis treatment. Supporting this therapeutic use, very recently it has been reported ginger derivatives (GDs) ability to control inflammation associated with different arthritis models. So the authors decided to study GDs toxicity, anti-catabolic and anti-inflammatory properties in cultured chondrocytes.
Materials and methods GDs toxicity was tested by MTT assay in cultured ATDC5 chondrocytes. Supernatant nitrite accumulation was determined by Griess reaction. Inducible nitric oxide synthase (NOS2), MyD88 and ERK protein expression was examined by western-blot. MMPs activity was tested by gelatin zymography. Cathepsin-K activity was evaluated by biochemical and biological assays in cultured human chondrocytes.
Results 6-shogaol and 10-gingerol, were isolated from ginger extracts. In addition, a new synthetic derivative was also designed, SSi6. MTT assay revealed that unlike 10-gingerol, 6-shogaol and SSi6 were not toxic at studied concentrations. All these compounds inhibited cathepsin-K activity, however, only 6-shogaol was able to inhibit nitrite accumulation in the culture medium of LPS stimulated chondrocytes. In contrast, neither 6-shogaol nor SSi6 were able to reduce significantly IL-1β induced nitrite accumulation. Moreover, 6-shogaol was able to inhibit LPS mediated ERK activation and NOS2 and MyD88 induced expression. In addition 6-shogaol inhibited MMP-2 and MMP-9 induction in the culture medium of LPS treated cells.
Conclusions Data obtained reveal new potential avenues for OA treatment based in GDs properties to inhibit cathepsin-K activity and 6-shogaol ability to inhibit innate immune inflammatory responses through TLR4 blockade.
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