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Rupestonic Acid of Artemisia Rupestris L. Extract Treats Pulmonary Fibrosis in COPD by Targeting TGF‐β1

Ling-Feng Peng,Lulu Zhang,Yi-meng Fan,Sijuan Huang,Qingyu Zhao,Chao Han,Zhihui Hao

Published 2026 in Advancement of science

ABSTRACT

Pulmonary fibrosis (PF) is the final stage of lung damage, such as chronic obstructive pulmonary disease (COPD), with no effective treatment. Transforming growth factor beta 1 (TGF‐β1) is a key protein involved in fibrosis and regulating inflammation. Therefore, targeting components of TGF‐β1 is an effective strategy for controlling PF. Artemisia rupestris L, a perennial herb of rupestris belonging to Artemisia, has been prescribed as a treatment for pulmonary inflammation. We investigated the effects and mechanisms of Artemisia rupestris L ethanol extract (EEAR) on PF induced by cigarette smoke (CS) in vitro and in vivo models. In addition, we used Biolayer Interferometry (BLI) and Liquid Chromatograph‐Mass Spectrometer (LC‐MS) to screen and identify compounds that bind to TGF‐β1 in EEAR. We found that EEAR inhibited PF, lung inflammation, and airway obstruction, thereby improving lung injury and blood oxygen levels in COPD. And we identified the active ingredient in EEAR that binds to TGF‐β1, rupestonic acid (RA). RA inhibited the TGF‐β1‐Smad2/3 signaling pathway by suppressing TGF‐β1 ubiquitination and changing its conformation. Furthermore, RA significantly inhibited epithelial mesenchymal transition (EMT) and collagen deposition, thereby treating PF. Based on these findings, we propose that RA might be a promising therapeutic drug candidate for treating PF.

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