Phlorofucofuroeckol A from Ecklonia cava ameliorates TGF-β1-induced fibrotic response of human tracheal fibroblasts via the downregulation of MAPKs and SMAD 2/3 pathways inactivated TGF-β receptor.

The objective of this study was to investigate inhibitory effects of a bioactive compound isolated from Ecklonia cava on fibrotic responses to transforming growth factor-β1 (TGF-β1)-stimulated Hs680. Tr human tracheal fibroblasts and the associated mechanisms of action. Post consecutive purification, a potent bioactive compound was identified phlorofucofuroeckol A. Phlorofucofuroeckol A significantly suppressed protein expression levels of collagen type I and α-smooth muscle actin (α-SMA) on TGF-β1-stimulated Hs680. Tr human tracheal fibroblasts. Further mechanistic studies determined that phlorofucofuroeckol A suppressed the phosphorylation of p38, extracellular regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) and SMAD 2/3 in TGF-β1-stimulated Hs680. Tr human tracheal fibroblasts. Moreover, we could show that phlorofucofuroeckol A inhibits binding of TGF-β1 to its TGF-β receptor by molecular docking. Based on the results, we propose that phlorofucofuroeckol A suppresses the MAPKs and SMAD 2/3 pathways and relieves cellular fibrotic activities, thus preventing tracheal fibrosis.