title: Baicalin inhibits hypoxia-induced pulmonary artery smooth muscle cell proliferation via the AKT/HIF-1α/p27-associated pathway.
abstract: Baicalin, a flavonoid compound purified from the dry roots of Scutellaria baicalensis Georgi, has been shown to possess various pharmacological actions. Previous studies have revealed that baicalin inhibits the growth of cancer cells through the induction of apoptosis. Pulmonary arterial hypertension (PAH) is a devastating disease characterized by enhanced pulmonary artery smooth muscle cell (PASMCs) proliferation and suppressed apoptosis. However, the potential mechanism of baicalin in the regulation of PASMC proliferation and the prevention of cardiovascular diseases remains unexplored. To test the effects of baicalin on hypoxia, we used rats treated with or without baicalin (100 mg·kg⁻¹ each rat) at the beginning of the third week after hypoxia. Hemodynamic and pulmonary pathomorphology data showed that right ventricular systolic pressures (RVSP), the weight of the right ventricle/left ventricle plus septum (RV/LV + S) ratio and the medial width of pulmonary arterioles were much higher in chronic hypoxia. However, baicalin treatment repressed the elevation of RVSP, RV/LV + S and attenuated the pulmonary vascular structure remodeling (PVSR) of pulmonary arterioles induced by chronic hypoxia. Additionally, baicalin (10 and 20 μmol·L⁻¹) treatment suppressed the proliferation of PASMCs and attenuated the expression of hypoxia-inducible factor-α (HIF-α) under hypoxia exposure. Meanwhile, baicalin reversed the hypoxia-induced reduction of p27 and increased AKT/protein kinase B phosphorylation p-AKT both in vivo and in vitro. These results suggested that baicalin could effectively attenuate PVSR and hypoxic pulmonary hypertension.
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian 116000, China. linzhangdr2014@163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Clinical Medicine, Yijishan Hospital of Wannan Medical College, Wuhu 241001, China. zhichenp@163.com.
authors.forename: Zhichen
authors.initials: Z
authors.lastname: Pu
authors.affiliation: Department of Oncology, Dalian University Affiliated Xinhua Hospital, No. 156 Wansui Street, Dalian 116000, China. junsongw0111@163.com.
authors.forename: Junsong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian 116000, China. zhifengzhang1981@163.com.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Public Health, Dalian Medical University, 9 Western Lvshun South Road, Dalian 116000, China. dongmeih1979@163.com.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian 116000, China. junjiewang@dlmedu.edu.cn.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000150:complications*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D031364:Scutellaria baicalensis / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005419:Flavonoids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C038044:baicalin; D051057:Proto-Oncogene Proteins c-akt