AUTHOR=Yu Xin , Xiao Li , Zhu Jiang , Sun Tianying , Gong Kai , Kou Xuefang , Zhou Yuhe , Xu Mengzhen , Lu Kaihui , Sun Hua , Guan Haixing , Liu Chuanguo 

TITLE=Pinostilbene inhibits lung epithelial-mesenchymal transition and delays pulmonary fibrosis by modulating the PI3K/Akt pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1614546

DOI=10.3389/fphar.2025.1614546

ISSN=1663-9812

ABSTRACT=Epithelial-mesenchymal transition (EMT) in the lung is a key process in which pulmonary epithelial cells lose epithelial characteristics and acquire mesenchymal properties, contributing to conditions such as pulmonary fibrosis. This study investigates the potential of pinostilbene (PIN), a natural stilbene compound with known anti-cancer, antioxidant and anti-inflammatory properties, to inhibit pulmonary EMT. Cellular experiments using A549 and Beas2B cells showed that PIN significantly reduced TGF-β1-induced mesenchymal marker expression while increasing epithelial marker expression. Functional assays confirmed the ability of PIN to inhibit cell migration and adhesion. In vivo, PIN alone or in combination with pirfenidone effectively alleviated lung damage in a murine lung fibrosis model, as demonstrated by histological analysis. Mechanistic studies identified the PI3K/Akt pathway as a target of PIN, with Western blot analysis showing decreased phosphorylation levels of PI3K and Akt. These findings suggest that PIN inhibits pulmonary EMT and delays the progression of pulmonary fibrosis by modulating the PI3K/Akt pathway, providing a promising therapeutic avenue for lung diseases associated with EMT.