Oxymatrine prevents hypoxia- and monocrotaline-induced pulmonary hypertension in rats.
Pulmonary hypertension is a progressive disease characterized by marked pulmonary arterial remodeling and increased vascular resistance. Inflammation and oxidative stress promote the development of pulmonary hypertension. Oxymatrine, one of the main active components of the Chinese herb Sophora flavescens Ait. (Kushen), plays anti-inflammatory and antioxidant protective roles, which effects on pulmonary arteries remain unclear. This study aimed to investigate the effects of oxymatrine on pulmonary hypertension development. Sprague-Dawley rats were exposed to hypoxia for 28 days or injected with monocrotaline, to develop pulmonary hypertension, along with administration of oxymatrine (50mg/kg/day). Hemodynamics and pulmonary arterial remodeling data from the rats were then obtained. The antiproliferative effect of oxymatrine was verified by in vitro assays. The inflammatory cytokine mRNA levels and leukocyte and T cell accumulation in lung tissue were detected. The antioxidative effects of oxymatrine were explored in vitro. Our study shows that oxymatrine treatment attenuated right-ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia or monocrotaline and inhibited proliferation of pulmonary arterial smooth muscle cells (PASMCs). Increased expression of inflammatory cytokine mRNA and accumulation of leukocytes and T cells around the pulmonary arteries were suppressed with oxymatrine administration. Under hypoxic conditions, oxymatrine significantly upregulated Nrf2 and antioxidant protein SOD1 and HO-1 expression, but downregulated hydroperoxide levels in PASMCs. In summary, this study indicates that oxymatrine may prevent pulmonary hypertension through its antiproliferative, anti-inflammatory, and antioxidant effects, thus providing a promising pharmacological avenue for treating pulmonary hypertension.
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China. Electronic address: luckzb@fmmu.edu.cn.
Bo
B
Zhang
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Wen
W
Niu
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Dunquan
D
Xu
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Yanyan
Y
Li
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Manling
M
Liu
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Yanxia
Y
Wang
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Ying
Y
Luo
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Pengtao
P
Zhao
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Yi
Y
Liu
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Mingqing
M
Dong
Xi'an YiLe Bio-Tech Laboratory, Xi'an 710075, People's Republic of China.
Rihe
R
Sun
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China. Electronic address: liyun8@fmmu.edu.cn.
Haiying
H
Dong
Department of Pathology, Xijing Hospital and Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, People's Republic of China. Electronic address: lizhic@fmmu.edu.cn.
Zhichao
Z
Li
D000818:Animals; D006801:Humans; D051381:Rats; D000470:Alkaloids / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D000860:Hypoxia / Q000188:drug therapy / Q000473:pathology; D016686:Monocrotaline / Q000633:toxicity; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D011651:Pulmonary Artery / Q000378:metabolism; D011807:Quinolizines / Q000008:administration & dosage; D013482:Superoxide Dismutase / Q000096:biosynthesis; D000072105:Superoxide Dismutase-1; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis; D000093842:Matrines
D000470:Alkaloids; D051547:Heme Oxygenase-1; D016686:Monocrotaline; D011807:Quinolizines; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D051267:NF-E2-Related Factor 2; C037573:oxymatrine; D000093842:Matrines; C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat; C495637:Nfe2l2 protein, rat
Free radicals; Hypoxia; Inflammation; Oxidative stress; Oxymatrine; Proliferation; Pulmonary hypertension