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Biomed Res Int. 2018 Feb 28;2018:1047810. doi: 10.1155/2018/1047810. eCollection 2018.

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

Yang D1,2,3, Tan S1,2, Yang Z4, Jiang P5, Qin C1,2, Yuan Q6, Dang R5, Yao X7, Qu J1,2, Lu Q1,2, Xu P1,2, Zhang B1,2, Xiang D1,2, Chen L1,2.

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


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.

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