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Magnolol ameliorates pneumonectomy and monocrotaline-induced pulmonary arterial hypertension in rats through inhibition of angiotensin II and endothelin-1 expression

Chang, Hung, Chang, Cheng-Yi, Lee, Hwei-Jen, Chou, Ching-Yu, Chou, Tz-Chong
Phytomedicine 2018 v.51 pp. 205-213
Magnolia officinalis, angiotensin II, bioactive compounds, endothelial nitric oxide synthase, endothelins, gene expression, histopathology, hypertension, hypertrophy, inducible nitric oxide synthase, lungs, magnolol, monocrotaline, peptidyl-dipeptidase A, protective effect, pulmonary artery, rats, signal transduction, superoxide anion, therapeutics
Background: Magnolol, a major bioactive component extracted from Magnolia officinalis, exerts several beneficial effects, such as anti-inflammatory and anti-hypertensive activities.Purpose: In this study, we investigated whether magnolol has a protective effect on pneumonectomy and monocrotaline-induced pulmonary arterial hypertension (PAH) in rats.Design/Methods: The alterations of right ventricular (RV) hypertrophy, pulmonary vascular remodeling, histopathological parameters, and related gene expression and signaling pathways in lungs by magnolol treatment were studied in the PAH rats.Results: Administration of magnolol greatly ameliorated the characteristic features of PAH, including increased pulmonary arterial pressure, RV hypertrophy, and pulmonary vascular remodeling. Moreover, magnolol inhibited angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/Ang II type 1 receptor (AT-1R) cascade, whereas upregulates ACE2 in the lungs of PAH rats. The overexpression of endothelin-1 (ET-1) and ETA receptor occurred in the PAH rats was significantly attenuated by magnolol through inhibition of Akt/ERK1/2/GSK3β/β-catenin pathway. Compared with that of untreated PAH rats, higher expression of endothelial nitric oxide synthase, and lower expression of inducible nitric oxide synthase and O2− production in lungs were observed in magnolol-treated PAH rats.Conclusion: We demonstrated that treatment with magnolol reduces the development of PAH induced by pneumonectomy and monocrotaline in rats, and suppressing Ang II and ET-1-mediated processes may contribute to its protective effects. These findings suggest that magnolol may be a potential agent for PAH therapy.