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

Seong-Yeong Heo; Min-Seon Jeong; Hyoung Shin Lee; Young Jick Kim; Sang-Hyug Park; Won-Kyo Jung

doi:10.1016/j.bbrc.2019.11.127

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

Biochem Biophys Res Commun. 2020 Feb 12;522(3):626-632. doi: 10.1016/j.bbrc.2019.11.127. Epub 2019 Nov 28.

Authors

Seong-Yeong Heo¹, Min-Seon Jeong², Hyoung Shin Lee³, Young Jick Kim⁴, Sang-Hyug Park¹, Won-Kyo Jung⁵

Affiliations

¹ Department of Biomedical Engineering, Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, 48513, Republic of Korea; Marine-Integrated Bionics Research Center, Pukyong National University, Busan, 48513, Republic of Korea.
² Department of Biomedical Engineering, Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, 48513, Republic of Korea; EONE-DIAGNOMICS Genome Center (EDGC), 291 Harmony-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea.
³ Department of Otolaryngology-Head and Neck Surgery, Kosin University College of Medicine, Busan, 49104, Republic of Korea.
⁴ ATEMs Co. Ltd., 306, Acekwanggyo Tower, 17 Daehak 4-ro, Yeongtong-gu, Suwon Gyeonggi, Republic of Korea.
⁵ Department of Biomedical Engineering, Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, 48513, Republic of Korea; Marine-Integrated Bionics Research Center, Pukyong National University, Busan, 48513, Republic of Korea. Electronic address: wkjung@pknu.ac.kr.

PMID: 31785808
DOI: 10.1016/j.bbrc.2019.11.127

Abstract

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.

Keywords: Anti-fibrosis; Ecklonia cava; Phlorofucofuroeckol A; Tracheal fibroblasts.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzofurans / chemistry
Benzofurans / pharmacology*
Cell Line
Dioxins / chemistry
Dioxins / pharmacology*
Fibroblasts / drug effects*
Fibroblasts / metabolism
Fibroblasts / pathology
Fibrosis
Humans
MAP Kinase Signaling System / drug effects
Phaeophyceae / chemistry
Signal Transduction / drug effects*
Smad2 Protein / metabolism
Smad3 Protein / metabolism
Trachea / drug effects*
Trachea / metabolism
Trachea / pathology
Transforming Growth Factor beta1 / metabolism*

Substances

Benzofurans
Dioxins
SMAD2 protein, human
SMAD3 protein, human
Smad2 Protein
Smad3 Protein
TGFB1 protein, human
Transforming Growth Factor beta1
phlorofucofuroeckol A