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Molecules 2014, 19(11), 19036-19049;

Antioxidant Mechanism of Rutin on Hypoxia-Induced Pulmonary Arterial Cell Proliferation

Department of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Nangang District, Harbin 150081, China
Bio-pharmaceutical Key Laboratory of Harbin, Harbin Medical University, Harbin 150081, China
Department of Pathophysiology, Harbin Medical University-Daqing, Daqing 163319, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 26 August 2014 / Revised: 28 September 2014 / Accepted: 9 October 2014 / Published: 18 November 2014
(This article belongs to the Section Natural Products Chemistry)
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Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4) in pulmonary artery endothelial cells (PAECs). Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α). Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC), a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation. View Full-Text
Keywords: rutin; reactive oxygen species (ROS); NADPH oxidase 4; proliferation; hypoxia rutin; reactive oxygen species (ROS); NADPH oxidase 4; proliferation; hypoxia

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Li, Q.; Qiu, Y.; Mao, M.; Lv, J.; Zhang, L.; Li, S.; Li, X.; Zheng, X. Antioxidant Mechanism of Rutin on Hypoxia-Induced Pulmonary Arterial Cell Proliferation. Molecules 2014, 19, 19036-19049.

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