4.6 Article

Antifibrotic effects of eupatilin on TGF-β1-treated human vocal fold fibroblasts

Journal

PLOS ONE
Volume 16, Issue 3, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0249041

Keywords

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Funding

  1. National Research Foundation of Korea (NRF) - Korea government Ministry of Science and ICT (MSIT) [2020R1G1A1004280]
  2. Catholic University of Korea Daejeon St. Mary's Hospital [CMCDJ-P-2019-003]
  3. E.N.T. Fund of the Catholic University of Korea [5-2020-B0001-00260]
  4. National Research Foundation of Korea [2020R1G1A1004280] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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Eupatilin has been shown to effectively suppress TGF-beta 1-induced fibrotic changes in human vocal fold fibroblasts through the Smad and p38 signaling pathways. This suggests that eupatilin may serve as a novel therapeutic agent for the treatment of vocal fold fibrosis. The study highlights the potential of eupatilin in inhibiting scar formation and promoting wound healing in the vocal fold tissue.
Vocal fold scarring is a major cause of dysphonia. Vocal fold fibroblasts (VFFs) and the TGF-beta signaling pathway play important roles in scar formation. Eupatilin, a chromone derivative of the Artemisia species, is a traditional folk remedy for wound healing. However, until recently, few studies investigated the therapeutic effects of eupatilin. We investigated the antifibrogenic effects of eupatilin on TGF-beta 1-treated human vocal fold fibroblasts (hVFFs). The optimal concentration of eupatilin was determined by a cell viability assay. Western blotting was used to measure the expression of alpha-smooth muscle actin during myofibroblast differentiation, fibronectin (FN), collagen type I (Col I), and collagen type III (Col III) extracellular matrix proteins, and Smad2, Smad3, and p38 in the fibrotic pathway. Measurements were made before and after eupatilin treatment. Eupatilin at 100 nM was shown to be safe for use in hVFFs. TGF-beta 1 induced hVFFs to proliferate and differentiate into myofibroblasts and increased Col III and FN synthesis in a time- and dose-dependent manner. Eupatilin suppressed TGF-beta 1-induced hVFF proliferation and differentiation into myofibroblasts through the Smad and p38 signaling pathways. Furthermore, eupatilin inhibited TGF-beta 1-induced FN, Col I, and Col III synthesis in hVFFs. Our in vitro findings show that eupatilin effectively suppressed TGF-beta 1-induced fibrotic changes in hVFFs via the Smad and p38 signaling pathways. Thus, eupatilin may be considered a novel therapeutic agent for the treatment of vocal fold fibrosis.

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