Hua Yu1, Jingjing Liu2, Yizhi Dong2, Min Xu3, Le Xu2, Huaqin Guan4, Xiaoru Xia5, Liangxing Wang6. 1. Department of Geriatric Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. 2. Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. 3. Department of Respiratory Medicine, Zhuji People's Hospital of Zhejiang Province, Zhuji, 311800, Zhejiang, China. 4. Department of Rheumatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. 5. Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. 6. Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. Electronic address: wanglx17@yeah.net.
Abstract
BACKGROUND: Previous studies have found that dihydroartemisinin (DHA) has multiple functions such as anti-inflammatory, anti-tumor in addition to anti-malarial effects. Effect of DHA on monocrotaline-induced pulmonary hypertension in rats has been reported, while the specific mechanism is not known. METHOD: A hypoxic model was established with human pulmonary arterial endothelial cells (HPAECs) to investigate the possible mechanism of DHA. Effects of DHA on proliferation of HPAECs were evaluated by CCK-8 and EdU assay. Effects of DHA on cell oxidative stress, cell migration, angiogenesis, cell cycle and autophagy, as well as the possible underlying mechanism were also detected by using the established normoxia/hypoxia cell models. RESULTS: DHA significantly inhibited hypoxia induced increase of HPAECs proliferation in a dose dependent manner, migratory ability and angiogenic ability. DHA also significantly reversed hypoxia induced oxidative stress as a reduction of ROS and NO, and an increase of SOD. Autophagosomes, LC3B protein and apoptotic proteins were significantly increased in DHA treated hypoxic HPAECs. Autophagy inhibitor 3-Methyladenine diminishes the anti-hypoxia effects of DHA on cell proliferation, migration, and autophagy and apoptosis protein expression in HPAECs. CONCLUSION: DHA effectively inhibits hypoxia induced increase of cell proliferation, migration, and oxidative stress in HPAECs, and autophagy may be the underlying mechanism of DHA.
BACKGROUND: Previous studies have found that dihydroartemisinin (DHA) has multiple functions such as anti-inflammatory, anti-tumor in addition to anti-malarial effects. Effect of DHA on monocrotaline-induced pulmonary hypertension in rats has been reported, while the specific mechanism is not known. METHOD: A hypoxic model was established with human pulmonary arterial endothelial cells (HPAECs) to investigate the possible mechanism of DHA. Effects of DHA on proliferation of HPAECs were evaluated by CCK-8 and EdU assay. Effects of DHA on cell oxidative stress, cell migration, angiogenesis, cell cycle and autophagy, as well as the possible underlying mechanism were also detected by using the established normoxia/hypoxia cell models. RESULTS:DHA significantly inhibited hypoxia induced increase of HPAECs proliferation in a dose dependent manner, migratory ability and angiogenic ability. DHA also significantly reversed hypoxia induced oxidative stress as a reduction of ROS and NO, and an increase of SOD. Autophagosomes, LC3B protein and apoptotic proteins were significantly increased in DHA treated hypoxic HPAECs. Autophagy inhibitor 3-Methyladenine diminishes the anti-hypoxia effects of DHA on cell proliferation, migration, and autophagy and apoptosis protein expression in HPAECs. CONCLUSION:DHA effectively inhibits hypoxia induced increase of cell proliferation, migration, and oxidative stress in HPAECs, and autophagy may be the underlying mechanism of DHA.
Authors: Matthew Mikhael; Christian Makar; Amir Wissa; Trixie Le; Mansoureh Eghbali; Soban Umar Journal: Front Physiol Date: 2019-09-24 Impact factor: 4.566
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