Ligustrazine Suppresses Platelet-Derived Growth Factor-BB-Induced Pulmonary Artery Smooth Muscle Cell Proliferation and Inflammation by Regulating the PI3K/AKT Signaling Pathway
| Autor: | Huiping Huang, Shaohua Luan, Lingjin Kong, Chuanzong Qi, Fanrong Wu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
China Myocytes Smooth Muscle Becaplermin Inflammation Pharmacology Rats Sprague-Dawley 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Right ventricular hypertrophy medicine Animals Protein kinase B PI3K/AKT/mTOR pathway 030304 developmental biology Cell Proliferation 0303 health sciences Pulmonary Arterial Hypertension Phosphoinositide 3-kinase Lung biology Akt/PKB signaling pathway business.industry Cell growth Plant Extracts Cell Cycle General Medicine medicine.disease Rats Disease Models Animal medicine.anatomical_structure Complementary and alternative medicine 030220 oncology & carcinogenesis Pyrazines biology.protein medicine.symptom business Proto-Oncogene Proteins c-akt |
| Zdroj: | The American journal of Chinese medicine. 49(2) |
| ISSN: | 1793-6853 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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