Fisetin alleviates pulmonary arterial hypertension by inhibiting the TGF-β1/Smad 2/3 signaling pathway.

Authors

Yanhong Xu, Shiwei Kang, Xiaowei Gong, Yadong Yuan

Published in

Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society. Volume 34. Issue 3. Jun 25, 2026. Epub Jun 25, 2026.

Abstract

Pulmonary arterial hypertension (PAH) is a refractory cardiopulmonary disorder with a high mortality rate and few treatment options. Fisetin, a natural flavonoid, exhibits pleiotropic effects including anti-angiogenic, anti-proliferative, anti-inflammatory, and autophagy-modulating activities. To evaluate the therapeutic potential of Fisetin, we established two experimental models: a rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and a platelet-derived growth factor (PDGF)-induced human pulmonary artery smooth muscle cell (PASMC) proliferation model. The therapeutic efficacy and underlying mechanisms of Fisetin were comprehensively assessed using a combination of in vivo and in vitro approaches, including right heart catheterization, masson's trichrome and hematoxylin-eosin staining, immunohistochemistry, westernblot, immunofluorescence, ELISA, and transmission electron microscopy. Additionally, Protein-protein docking predicts interactions between proteins, whereas molecular docking predicts interactions between small molecules and proteins. Fisetin significantly ameliorated pulmonary vascular remodeling and reduced both right ventricular systolic pressure and the right ventricular hypertrophy index in monocrotaline (MCT)-induced PAH rats. The underlying mechanism may involve suppression of the TGF-β1/Smad2/3 pathway, which regulates autophagy, cell proliferation, migration, and inflammatory responses. In vitro, Fisetin exerted a dose-dependent suppressive effect on these molecular events. This study suggests that Fisetin may alleviate MCT-induced PAH rats by suppressing aberrant TGF-β1/Smad2/3 pathway activation. These findings provide experimental and theoretical support for Fisetin as a promising therapeutic candidate for PAH.

PMID:
42347890
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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