Paeoniflorin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing TAK1-MAPK/NF-κB pathways.
Int J Med Sci
; 19(4): 681-694, 2022.
Article
en En
| MEDLINE
| ID: mdl-35582418
ABSTRACT
Pulmonary arterial hypertension (PAH) characterized by pulmonary vascular remodeling is a lethal disease. Paeoniflorin (PF) is a monoterpene glycoside with numerous beneficial functions, such as vasodilation, anti-inflammation and immunomodulation. This study aims to investigate the effects of PF on monocrotaline (MCT)-induced PAH rats. Our data showed that both prophylactic or therapeutic administration of PF alleviated MCT-induced increasing of right ventricular systolic pressure (RVSP), prevented right ventricle hypertrophy and pulmonary arterial remodeling, as well as inhibited inflammatory cell infiltration around pulmonary arteries. Meanwhile, PF blocked MCT-induced endothelial-mesenchymal transition (EndMT) as indicated by the restored expression of endothelial markers in lung. Moreover, PF inhibited MCT-induced down-regulation of bone morphogenetic protein receptor 2 (BMPR2) and suppressed MCT-induced phosphorylation of transforming growth factor-ß (TGFß) activated kinase 1 (TAK1) in vivo. In vitro studies indicated that PF prevented human pulmonary arterial smooth muscle cells (PASMCs) from platelet-derived growth factor-BB (PDGF-BB)-stimulated proliferation and migration. PF also partially reversed TGFß1, interleukin-1ß (IL-1ß) and tumor necrosis factor (TNF-α) co-stimulated endothelial-to-mesenchymal transition (EndMT) in cultured human pulmonary artery endothelial cells (HPAECs). Signaling pathway analysis demonstrated that the underlying mechanism might be associated with the inhibition of TAK1-MAPK/NF-κB pathways. Taken together, our results suggested that PF could be a potential drug for the treatment of PAH.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Hipertensión Arterial Pulmonar
/
Hipertensión Pulmonar
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Med Sci
Asunto de la revista:
MEDICINA
Año:
2022
Tipo del documento:
Article