Forsythoside B Mitigates Monocrotaline-Induced Pulmonary Arterial Hypertension via Blocking the NF-κB Signaling Pathway to Attenuate Vascular Remodeling.
Drug Des Devel Ther
; 18: 767-780, 2024.
Article
in En
| MEDLINE
| ID: mdl-38495631
ABSTRACT
Purpose:
Pulmonary arterial hypertension (PAH) is a devastating disease with little effective treatment. The proliferation of pulmonary artery smooth muscle cells (PASMCs) induced by the nuclear factor-κB (NF-κB) signaling activation plays a pivotal role in the pathogenesis of PAH. Forsythoside B (FTSâ¢B) possesses inhibitory effect on NF-κB signaling pathway. The present study aims to explore the effects and mechanisms of FTSâ¢B in PAH.Methods:
Sprague-Dawley rats received monocrotaline (MCT) intraperitoneal injection to establish PAH model, and FTSâ¢B was co-treated after MCT injection. Right ventricular hypertrophy and pulmonary artery pressure were measured by echocardiography and right heart catheterization, respectively. Histological alterations were detected by H&E staining and immunohistochemistry. FTSâ¢B's role in PASMC proliferation and migration were evaluated by CCK-8 and wound healing assay. To investigate the underlying mechanisms, Western blotting, immunofluorescence staining and ELISA were conducted. The NF-κB activator PMA was used to investigate the role of NF-κB in FTSâ¢B's protective effects against PAH.Results:
FTSâ¢B markedly alleviated MCT-induced vascular remodeling and pulmonary artery pressure, and improved right ventricular hypertrophy and survival. FTSâ¢B also reversed PDGF-BB-induced PASMC proliferation and migration, decreased PCNA and CyclinD1 expression in vitro. The elevated levels of IL-1ß and IL-6 caused by MCT were decreased by FTSâ¢B. Mechanistically, MCT-triggered phosphorylation of p65, IκBα, IKKα and IKKß was blunted by FTSâ¢B. FTSâ¢B also reversed MCT-induced nuclear translocation of p65. However, all these protective effects were blocked by PMA-mediated NF-κB activation.Conclusion:
FTSâ¢B effectively attenuates PAH by suppressing the NF-κB signaling pathway to attenuate vascular remodeling. FTSâ¢B might be a promising drug candidate with clinical translational potential for the treatment of PAH.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Caffeic Acids
/
Pulmonary Arterial Hypertension
/
Glucosides
/
Hypertension, Pulmonary
Limits:
Animals
Language:
En
Journal:
Drug Des Devel Ther
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2024
Document type:
Article