Phytoestrogen BAVACHIN (cas 19879-32-4) mediates anti-inflammation targeting IκB kinase-IκBα-NF-κB signaling pathway in chondrocytes in vitro

Add time:09/26/2019    Source:infona.pl

The pro-inflammatory cytokine interleukin-1beta (IL-1β) plays critical roles in pathogenesis of osteoarthritis. Although estrogen is protective for cartilage in osteoarthritis patients, it also potentially increases the risk of stroke and cancer. Phytoestrogens acting as natural estrogen receptor modulators may serve as alternatives. This study aimed to identify medicinal phytoestrogens that preserve anti-inflammatory property and may function as potential chondro-protective compounds. Both human chondrocytes and chondrocytic cell line CHON-002 were used for this study. Protein concentrations or expressions were measured by ELISA or Western blot, respectively. The DNA-binding activity and transcriptional activity of transcription factors were evaluated by electrophoretic mobility shift assay and dual-luciferase reporter assay, respectively. Cell migration was analyzed by chemotaxis assays. We found that among screened phytoestrogens, BAVACHIN (cas 19879-32-4) could potently decrease IL-1β-induced nuclear factor-kappa B (NF-κB) but not activator protein-1 (AP-1) DNA-binding activity. Bavachin also inhibited IκBα degradation, increased nuclear translocation of p65 and p50 as well as decreased IκBα kinase (IKK) activity. Furthermore, bavachin inhibited IL-1β-induced chemokine production that resulted in reduced migration of THP-1 monocytic cells. Our results suggest that through decreasing IL-1β-induced activation of IKK-IκBα-NF-κB signaling pathway, bavachin potentially protects cartilage from inflammation-mediated damage in joints of osteoarthritis patients.

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