title: WIN-34B, a new herbal medicine, inhibits the inflammatory response by inactivating IκB-α phosphorylation and mitogen activated protein kinase pathways in fibroblast-like synoviocytes.
abstract: BACKGROUND
  The dried flowers of Lonicera japonica Thunb and dried roots of Anemarrhena asphodeloides BUNGE have been used for the treatment of a variety of inflammatory diseases in traditional Korean medicine.
  
  
  OBJECTIVE
  The aim of the study is to evaluate the anti-inflammatory effects of WIN-34B, a new herbal medicine, in fibroblast-like synoviocytes (FLS) obtained from patients with osteoarthritis (OA).
  
  
  METHODS
  WIN-34B is isolated from the n-butanol fraction of dried flowers of L. japonica and dried roots of A. asphodeloides. The anti-inflammatory effects of WIN-34B on cell viability, the production and release of inflammatory mediators, matrix metalloproteinases (MMPs), aggrecanases, tissue inhibitor of matrix proteinases (TIMP) is compared with celecoxib in IL-1β-stimulated human OA FLS. Furthermore, the effect of WIN-34B on inhibitory kappa B-α (IκB-α) phosphorylation and mitogen-activated protein kinases (MAPK) in the IL-1β-stimulated OA FLS was also evaluated.
  
  
  RESULTS
  WIN-34B significantly inhibited the IL-1β-induced cell viability in human OA FLS without cytotoxicity. Compared to celecoxib, WIN-34B exhibited similar or better anti-inflammatory effects through significant suppression of inflammatory mediators (IL-1β, TNF-α, PGE2 and NO), MMPs (MMP-1, MMP-3 and MMP-13) and aggrecanases (ADAMTS-4 and ADAMTS-5), and enhancement of TIMPs (TIMP-1 and TIMP-3). Moreover, WIN-34B reduced the phosphorylation of IκB-α, ERK1/2, p38 and JNK1/2 in IL-1β-stimulated OA FLS.
  
  
  CONCLUSIONS
  WIN-34B exhibited similar or better anti-inflammatory properties in IL-1β-stimulated OA FLS compared to celecoxib. The anti-inflammatory effects of WIN-34B are due to inhibition of inflammatory mediators (IL-1β, TNF-α, PGE2 and NO) and regulation of MMPs, ADAMTSs and TIMPs via the inhibition of IκB-α and MAPK phosphorylation in IL-1β-stimulated OA FLS.
authors.affiliation: Oriental Medicine Research Center for Bone and Joint Disease, East-West Bone and Joint Research Institute, Kyung Hee University, 149 Sangil-dong, Gangdong-gu, Seoul 134-727, Republic of Korea. jehuh2551@hanmail.net
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Huh
authors.forename: Byung-Kwan
authors.initials: BK
authors.lastname: Seo
authors.forename: Yeon-Cheol
authors.initials: YC
authors.lastname: Park
authors.forename: Jong-In
authors.initials: JI
authors.lastname: Kim
authors.forename: Jae-Dong
authors.initials: JD
authors.lastname: Lee
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Choi
authors.forename: Yong-Hyeon
authors.initials: YH
authors.lastname: Baek
authors.forename: Dong-Suk
authors.initials: DS
authors.lastname: Park
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000368:Aged; D031403:Anemarrhena; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta; D031239:Lonicera; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; C000606204:NFKBIA protein, human; D010936:Plant Extracts; C560822:TIMP1 protein, human; C088390:TIMP3 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; C569023:WIN 34B; D000072000:NF-KappaB Inhibitor alpha; D020928:Mitogen-Activated Protein Kinases; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D020782:Matrix Metalloproteinases; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human