phytoestrogens and bavachin

The aim of this study was to examine the anabolic and anticatabolic functions of bavachin in primary rat chondrocytes. With bavachin treatment, chondrocytes survived for 21 d without cell proliferation, and the proteoglycan content and extracellular matrix increased. Short-term monolayer culture of chondrocytes showed that gene induction of both aggrecan and collagen type II, major extracellular matrix components, was significantly upregulated by bavachin. The expression and activities of cartilage-degrading enzymes such as matrix metalloproteinases and a disintegrin and metalloproteinase with thrombospondin motifs were inhibited significantly by bavachin, while tissue inhibitors of metalloprotease were significantly upregulated. Bavachin inhibits the expression of inducible nitric oxide synthase, a representative catabolic factor, and downregulated the expression of nitric oxide, cyclooxygenase-2, and prostaglandin E2 in a dose-dependent manner in chondrocytes. Our results suggest that the bavachin has anabolic and potent anticatabolic biological effects on chondrocytes, which may have considerable promise in treating articular cartilage degeneration in the future.

Topics: Animals; Cartilage, Articular; Cell Proliferation; Cells, Cultured; Chondrocytes; Collagen Type II; Cyclooxygenase 2 Inhibitors; Dinoprostone; Disintegrins; Extracellular Matrix; Flavonoids; Interleukin-1beta; Matrix Metalloproteinases; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis; Phytoestrogens; Phytotherapy; Plant Extracts; Proteoglycans; Psoralea; Rats, Sprague-Dawley; Thrombospondins

The pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) 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 could potently decrease IL-1 beta-induced nuclear factor-kappa B (NF-kappaB) but not activator protein-1 (AP-1) DNA-binding activity. Bavachin also inhibited I kappaB alpha degradation, increased nuclear translocation of p65 and p50 as well as decreased I kappaB alpha kinase (IKK) activity. Furthermore, bavachin inhibited IL-1 beta-induced chemokine production that resulted in reduced migration of THP-1 monocytic cells. Our results suggest that through decreasing IL-1 beta-induced activation of IKK-I kappaB alpha-NF-kappaB signaling pathway, bavachin potentially protects cartilage from inflammation-mediated damage in joints of osteoarthritis patients.

Topics: Anti-Inflammatory Agents; Cell Line; Chemokines; Chondrocytes; DNA; Dose-Response Relationship, Drug; Down-Regulation; Drugs, Chinese Herbal; Female; Flavonoids; Humans; I-kappa B Kinase; I-kappa B Proteins; Interleukin-1beta; NF-kappa B; NF-KappaB Inhibitor alpha; Phytoestrogens; Psoralea; Signal Transduction; Transcription Factor AP-1