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Ligustrazine Suppresses Platelet-Derived Growth Factor-BB-Induced Pulmonary Artery Smooth Muscle Cell Proliferation and Inflammation by Regulating the PI3K/AKT Signaling Pathway.
- Source :
- American Journal of Chinese Medicine; 2021, Vol. 49 Issue 2, p437-459, 23p
- Publication Year :
- 2021
-
Abstract
- Pulmonary arterial hypertension (PAH) is a serious pulmonary vascular disease. Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role in the course of this disease. Ligustrazine is an alkaloid monomer extracted from the rhizome of the herb Ligusticum chuanxiong. It is often used to treat cardiovascular diseases, but its effect on PAH has rarely been reported. This study aims to explore the protective effect and mechanism of ligustrazine on PAH. In the in vivo experiment, monocrotaline (MCT) was used to induce PAH in rats, and then ligustrazine (40, 80, 160 mg/kg/day) or sildenafil (25 mg/kg/day) was administered. Four weeks later, hemodynamic changes, right ventricular hypertrophy index, lung morphological characteristics, inflammatory factors, phosphoinositide 3-kinase (PI3K), and AKT expression were evaluated. In addition, primary rat PASMCs were extracted by the tissue adhesion method, a proliferation model was established with platelet-derived growth factor-BB (PDGF-BB), and the cells were treated with ligustrazine to investigate its effects on cell proliferation, inflammation, and cell cycle distribution. The results indicate that ligustrazine can markedly alleviate right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodeling, and inflammation caused by MCT, and that it decreased PI3K and AKT phosphorylation expression. Moreover, ligustrazine can inhibit the proliferation and inflammation of PASMCs and arrest the progression of G0/G1 to S phase through the PI3K/AKT signaling pathway. Therefore, we conclude that ligustrazine may inhibit the proliferation and inflammation of PASMCs by regulating the activation of the PI3K/AKT signaling pathway, thereby attenuating MCT-induced PAH in rats. Collectively, these findings suggest that ligustrazine may be a promising therapeutic for PAH. [ABSTRACT FROM AUTHOR]
- Subjects :
- PULMONARY hypertension prevention
INFLAMMATION prevention
LUNG anatomy
TISSUE analysis
MEDICINAL plants
IN vivo studies
SILDENAFIL
CENTRAL venous pressure
CATTLE
CELL culture
ALKALOIDS
ANIMAL experimentation
PULMONARY hypertension
RIGHT ventricular hypertrophy
FLUOROIMMUNOASSAY
WESTERN immunoblotting
ONE-way analysis of variance
PULMONARY artery
VASCULAR smooth muscle
CELLULAR signal transduction
PLANT roots
RATS
PATIENT monitoring
GENE expression
CELL survival
CELL cycle
T-test (Statistics)
CELL proliferation
TRANSFERASES
RESEARCH funding
DESCRIPTIVE statistics
PLANT extracts
HEMODYNAMICS
INFLAMMATORY mediators
BIOLOGICAL assay
CELL separation
DATA analysis software
PLATELET-derived growth factor
PHOSPHORYLATION
RADIOIMMUNOASSAY
Subjects
Details
- Language :
- English
- ISSN :
- 0192415X
- Volume :
- 49
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- American Journal of Chinese Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 149378353
- Full Text :
- https://doi.org/10.1142/S0192415X21500208