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BioMed Research International
Volume 2018 (2018), Article ID 1047810, 12 pages
Research Article

Dihydromyricetin Attenuates TNF-α-Induced Endothelial Dysfunction through miR-21-Mediated DDAH1/ADMA/NO Signal Pathway

1Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
2Institute of Clinical Pharmacy, Central South University, Changsha, Hunan 410011, China
3Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
4Department of Pharmacy, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Hunan 530021, China
5Department of Clinical Pharmacy and Pharmacology, Jining First People’s Hospital, Jining Medical University, Jining 272000, China
6New Drugs Innovation and Development Institute, Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, China
7Department of Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

Correspondence should be addressed to Lei Chen

Received 18 October 2017; Accepted 24 January 2018; Published 28 February 2018

Academic Editor: Ramazan Akdemir

Copyright © 2018 Dafeng Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Accumulating studies demonstrate that dihydromyricetin (DMY), a compound extracted from Chinese traditional herb, Ampelopsis grossedentata, attenuates atherosclerotic process by improvement of endothelial dysfunction. However, the underlying mechanism remains poorly understood. Thus, the aim of this study is to investigate the potential mechanism behind the attenuating effects of DMY on tumor necrosis factor alpha- (TNF-α-) induced endothelial dysfunction. In response to TNF-α, microRNA-21 (miR-21) expression was significantly increased in human umbilical vein endothelial cells (HUVECs), in line with impaired endothelial dysfunction as evidenced by decreased tube formation and migration, endothelial nitric oxide synthase (eNOS) (ser1177) phosphorylation, dimethylarginine dimethylaminohydrolases 1 (DDAH1) expression and metabolic activity, and nitric oxide (NO) concentration as well as increased asymmetric dimethylarginine (ADMA) levels. In contrast, DMY or blockade of miR-21 expression ameliorated endothelial dysfunction in HUVECs treated with TNF-α through downregulation of miR-21 expression, whereas these effects were abolished by overexpression of miR-21. In addition, using a nonspecific NOS inhibitor, L-NAME, also abrogated the attenuating effects of DMY on endothelial dysfunction. Taken together, these data demonstrated that miR-21-mediated DDAH1/ADMA/NO signal pathway plays an important role in TNF-α-induced endothelial dysfunction, and DMY attenuated endothelial dysfunction induced by TNF-α in a miR-21-dependent manner.