1. 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
- Author
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Dong-Suk Park, Jeong-Eun Huh, Jong-In Kim, Yong-Hyeon Baek, Byung-Kwan Seo, Do-Young Choi, Yeon-Cheol Park, and Jae-Dong Lee
- Subjects
MAPK/ERK pathway ,p38 mitogen-activated protein kinases ,Interleukin-1beta ,Anti-Inflammatory Agents ,Pharmacology ,Matrix metalloproteinase ,Anemarrhena asphodeloides ,NF-KappaB Inhibitor alpha ,Drug Discovery ,Humans ,Medicine ,Viability assay ,Phosphorylation ,Cells, Cultured ,Aged ,Cell Proliferation ,Tissue Inhibitor of Metalloproteinase-3 ,Anemarrhena ,Plants, Medicinal ,Tissue Inhibitor of Metalloproteinase-1 ,biology ,Plant Extracts ,Kinase ,business.industry ,Synovial Membrane ,Middle Aged ,biology.organism_classification ,Matrix Metalloproteinases ,ADAM Proteins ,Lonicera ,Mitogen-activated protein kinase ,Immunology ,ADAMTS4 Protein ,biology.protein ,I-kappa B Proteins ,ADAMTS5 Protein ,Mitogen-Activated Protein Kinases ,Procollagen N-Endopeptidase ,business - 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.
- Published
- 2012