Phytoestrogen bavachin mediates anti-inflammation targeting Ikappa B kinase-I kappaB alpha-NF-kappaB signaling pathway in chondrocytes in vitro.
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.
Cheng
Cheng-Chung
CC
Division of Cardiology, Department of Medicine, Tri-Service General Hospital, Taiwan, ROC.
Chen
Yi-Hsin
YH
Chang
Wen-Liang
WL
Yang
Shih-Ping
SP
Chang
Deh-Ming
DM
Lai
Jenn-Haung
JH
Ho
Ling-Jun
LJ
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D048789:Phytoestrogens / Q000494:pharmacology*; D029907:Psoralea / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D048789:Phytoestrogens; D018808:Transcription Factor AP-1; C459212:bavachin; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D051550:I-kappa B Kinase