Pinostilbene Inhibits Lung Epithelial-Mesenchymal Transition and Delays Pulmonary Fibrosis by Modulating the PI3K/Akt Pathway

Xin Yu¹Xiao Li²Xuefang Kou³Yuhe Zhou¹Mengzhen Xu¹Kaihui Lu¹Kai Gong¹Jiang Zhu¹Tianying Sun¹Hua Sun⁴Haixing Guan^3,5Chuanguo Liu^3,5*

• ¹山东中医药大学中医药创新研究院, 山东-济南市-长清区, China
• ²Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
• ³Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
• ⁴Department of Medical Oncology, Shandong Cancer Hospital, Shandong University, Jinan, Shandong Province, China
• ⁵Key Laboratory of Traditional Chinese Medicine Classic Theory, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China

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 (PEMT). 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 PEMT and delays the progression of pulmonary fibrosis by modulating the PI3K/Akt pathway, providing a promising therapeutic avenue for lung diseases associated with EMT.