title: Honokiol, a low molecular weight natural product, prevents inflammatory response and cartilage matrix degradation in human osteoarthritis chondrocytes.
abstract: Proinflammatory cytokine interleukin-1β (IL-1β) stimulates several mediators of cartilage degradation and plays an important role in the pathogenesis of osteoarthritis (OA). Honokiol, a low molecular weight natural product isolated from the Magnolia officinalis, has been shown to possess anti-inflammatory effect. Here, we used an in vitro model of cartilage inflammation to investigate the therapeutic potential of honokiol in OA. Human OA chondrocytes were cultured and pretreated with honokiol (2.5-10 µM) with or without IL-1β (10 ng/ml). Nitric oxide (NO) production was quantified by Griess reagent. Prostaglandin (PG)E2 , metalloproteinase-13 (MMP-13), and interleukin-6 (IL-6) productions were quantified by enzyme-linked immunosorbent assay. The expressions of collagen II, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor κB (NF-κB)-related signaling molecules were determined by Western blotting. Our data showed that IL-1β markedly stimulated the expressions of iNOS and COX-2 and the productions of NO, PGE2 , and IL-6, which could be significantly reversed by honokiol. Honokiol could also suppress the IL-1β-triggered activation of IKK/IκBα/NF-κB signaling pathway. Moreover, honokiol significantly inhibited the IL-1β-induced MMP-13 production and collagen II reduction. Taken together, the present study suggests that honokiol may have a chondroprotective effect and may be a potential therapeutic choice in the treatment of OA patients.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, No.1, Jen-Ai Road, Section 1, Taipei, 10051, Taiwan.
authors.forename: Ying Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Keh Sung
authors.initials: KS
authors.lastname: Tsai
authors.forename: Ding Cheng
authors.initials: DC
authors.lastname: Chan
authors.forename: Kuo Cheng
authors.initials: KC
authors.lastname: Lan
authors.forename: Cheng Feng
authors.initials: CF
authors.lastname: Chen
authors.forename: Rong Sen
authors.initials: RS
authors.lastname: Yang
authors.forename: Shing Hwa
authors.initials: SH
authors.lastname: Liu
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D031566:Magnolia; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D024043:Collagen Type II; D004365:Drugs, Chinese Herbal; D051550:I-kappa B Kinase; D017705:Lignans; D053509:Matrix Metalloproteinase 13; D016328:NF-kappa B; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C507079:MMP13 protein, human
keywords: MMP-13; chondrocyte; collagen II; honokiol; osteoarthritis