ReferenceID 5521

Protective effects of isorhamnetin on pulmonary arterial hypertension: in vivo and in vitro studies

Phytother Res

Pulmonary arterial hypertension (PAH) is a malignant disease with high mortality and closely involves the bone morphogenetic protein (BMP) pathway. Mutations in BMPR2 caused proliferation of pulmonary artery smooth muscl

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Reference Id
5521
Evidence Id
22111
Core Evidence Id
22111
Source Reference Id
4281
Herb2 Reference Id
HBREF005078
Subject Paper Key
HBIN031114_32452118
Pubmed Id
32452118
Doi
10.1002/ptr.6714
Paper Title
Protective effects of isorhamnetin on pulmonary arterial hypertension: in vivo and in vitro studies
Paper Abstract
Pulmonary arterial hypertension (PAH) is a malignant disease with high mortality and closely involves the bone morphogenetic protein (BMP) pathway. Mutations in BMPR2 caused proliferation of pulmonary artery smooth muscle cells (PASMCs) leading to PAH. Isorhamnetin, one of the main naturally occurring flavonoids extracted from Hippophae rhamnoides L, shows antiinflammatory and anti-proliferative properties. Nevertheless, the effects of isorhamnetin on PAH remain unclear. This study aimed to investigate whether isorhamnetin has protective effects against PAH and explore possible mechanisms. An in vivo model of PAH induced by monocrotaline (MCT) was employed, and sildenafil and isorhamnetin were orally administered for 21 consecutive days. An in vitro model induced by TNF-alpha was employed, and cell proliferation of HPASMCs was detected. Results indicated that isorhamnetin significantly improved hemodynamic, histopathological, and echocardiographic changes in MCT-induced PAH in rats. In vitro, isorhamnetin suppressed TNF-alpha-induced HPASMCs proliferation. Furthermore, isorhamnetin improved protein expression of BMPR2 and suppressed protein expression of TNF-alpha and IL-6 in rat lungs. Isorhamnetin improved protein expression of BMPR2 and p-smad1/5 and mRNA expression of Id1 and Id3 in HPASMCs. Isorhamnetin ameliorated MCT-induced PAH in rats and inhibited TNF-alpha-induced HPASMCs proliferation by a mechanism likely involving the regulation of the BMP signaling pathway.
Journal
Phytother Res
Publish Year
2020
Experiment Subject
rat
Experiment Type
Animal & Cell Experiment
Phenotype Related
Pulmonary Arterial Hypertension; Malignant Disease
Paper Title Cn
Paper Title En
Protective effects of isorhamnetin on pulmonary arterial hypertension: in vivo and in vitro studies
Bilingual Status
semi_complete