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

J Ethnopharmacol. 2012 Oct 11;143(3):779-86. doi: 10.1016/j.jep.2012.06.041. Epub 2012 Aug 1.

Abstract

Ethnopharmacological relevance: 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).

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / metabolism
  • ADAMTS4 Protein
  • ADAMTS5 Protein
  • Aged
  • Anemarrhena*
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Humans
  • I-kappa B Proteins / metabolism
  • Interleukin-1beta
  • Lonicera*
  • Matrix Metalloproteinases / metabolism
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-KappaB Inhibitor alpha
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Procollagen N-Endopeptidase / metabolism
  • Synovial Membrane / cytology*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism

Substances

  • Anti-Inflammatory Agents
  • I-kappa B Proteins
  • Interleukin-1beta
  • NFKBIA protein, human
  • Plant Extracts
  • TIMP1 protein, human
  • TIMP3 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-3
  • WIN 34B
  • NF-KappaB Inhibitor alpha
  • Mitogen-Activated Protein Kinases
  • ADAM Proteins
  • ADAMTS5 Protein
  • ADAMTS5 protein, human
  • Matrix Metalloproteinases
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein
  • ADAMTS4 protein, human