239 Berberine Inhibits Myofibroblast Differentiation in Nasal Polyp-deroved Fibroblast via P-38 Pathway

BACKGROUND: The alkaloid has shown pharmacological activities and multiple biological functions such as antibiotic activity, anti-tumor, anti-inflammation and anti-fibrotic properties. The purposes of this study were to examine whether berberine has any effect on phenotype change and extracellular matrix production in nasal polyp-derived fibroblasts (NPDFs) and to investigate underlying molecular mechanism. METHODS: NPDFs were pre-treated with berberin for 2 hours prior to induction by transforming growth factor (TGF)-β1. The expression of α-smooth muscle actin (SMA) and collagen type I mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of α-SMA protein and collagen type I was determined by Westernblotting and/or immunofluoescent staining. Total soluble collagen production was analyzed by the SirCol collagen dye-binding assay. Expression of pSmad 2/3, pp38, pERK 1/2 and pJNK was evaluated by Western blot analysis. RESULTS: In TGF-β1-induced NPDFs, berberine significantly inhibited the expressions of α-SMA and collagen type I mRNA and reduced α-SMA and collagen protein levels. Berberine had no effect on the level of pSmad2/3, pERK1/2 and pJNK expression in TGF-β1-induced NPDFs. However, berberine suppressed the expression of phosphorylated p38 in TGF-β1-induced NPDFs. SB 203580 (a specific inhibitor of p38 kinase) markedly suppresse the increased expression of collagen type I and α-smooth muscle actin (α-SMA) protein in TGF-β1-induced NPDFs. CONCLUSIONS: Berberine exerts suppressive effects on phenotype change and extracellular matrix production in NPDFs, through interfering of p38 signaling pathways. Our findings provide new therapeutic options for extracellular matrix production in nasal polyps.