Phlorotannins ameliorate extracellular matrix production in human vocal fold fibroblasts and prevent vocal fold fibrosis via aerosol inhalation in a laser‐induced fibrosis model

Vocal fold fibrosis is an abnormal condition characterized by unfavorable changes in the organization of the extracellular matrix in vocal fold lamina propria. To prevent and treat vocal fold fibrosis, a number of synthetic drugs, such as mitomycin C and the glucocorticoid family, are used after surgery, but these are known to have some side effects. Therefore, using both in vitro and in vivo studies, this study investigated whether phlorotannins extracted from Ecklonia cava have the potential to prevent vocal fold fibrosis with minimal side effects. The results show that phlorotannins suppressed both the expression of the fibrotic phenotypic marker and cell migration by inhibiting the activation of the mitogen‐activated protein kinase (MAPK) and Smad2/3 signaling pathways in human vocal fold fibroblasts stimulated by transforming growth factor‐β. Additionally, phlorotannins exhibited antifibrotic efficacy without an excessive inflammatory response in a laser‐induced fibrosis rabbit model when delivered as an aerosol via inhalation. Based on these results, phlorotannins should be considered a promising candidate for use in the prevention of vocal fold fibrosis.