2. Academic Validation
  3. Protective Effects and Mechanisms of Vaccarin on Vascular Endothelial Dysfunction in Diabetic Angiopathy

Protective Effects and Mechanisms of Vaccarin on Vascular Endothelial Dysfunction in Diabetic Angiopathy

  • Int J Mol Sci. 2019 Sep 17;20(18):4587. doi: 10.3390/ijms20184587.
Fei Xu 1,  Yixiao Liu 2,  Xuexue Zhu 3,  Shuangshuang Li 4,  Xuelin Shi 5,  Zhongjie Li 6,  Min Ai 7,  Jiangnan Sun 8,  Bao Hou 9,  Weiwei Cai 10,  Haijian Sun 11,  Lulu Ni 12,  Yuetao Zhou 13,  Liying Qiu 14
Affiliations

Affiliations

  • 1 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. feixuhgd@163.com.
  • 2 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. 18861824121@163.com.
  • 3 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. xuexue.zhu1992@gmail.com.
  • 4 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. Liss_1@163.com.
  • 5 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. sxlgeneral@163.com.
  • 6 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. 6171504016@stu.jiangnan.edu.cn.
  • 7 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. 6182806001@stu.jiangnan.edu.cn.
  • 8 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. 6182806005@stu.jiangnan.edu.cn.
  • 9 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. houbao2015@163.com.
  • 10 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. caiweiwei@jiangnan.edu.cn.
  • 11 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. sunhaijian927@163.com.
  • 12 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. nllandylau002@163.com.
  • 13 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. yuetaozhou@126.com.
  • 14 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214100, China. qiulydoc@sina.com.
PMID: 31533227 DOI: 10.3390/ijms20184587
Abstract

Cardiovascular complications are a major leading cause of mortality in patients suffering from type 2 diabetes mellitus (T2DM). Vascular endothelial dysfunction is a core pathophysiological event in the early stage of T2DM and eventually leads to Cardiovascular Disease. Vaccarin (VAC), an active flavonoid glycoside extracted from vaccariae semen, exhibits extensive biological activities including vascular endothelial cell protection effects. However, little is known about whether VAC is involved in endothelial dysfunction regulation under high glucose (HG) or hyperglycemia conditions. Here, in an in vivo study, we found that VAC attenuated increased blood glucose, increased glucose and Insulin tolerance, relieved the disorder of lipid metabolism and oxidative stress, and improved endothelium-dependent vasorelaxation in STZ/HFD-induced T2DM mice. Furthermore, in cultured human microvascular endothelial cell-1 (HMEC-1) cells, we showed that pretreatment with VAC dose-dependently increased nitric oxide (NO) generation and the phosphorylation of eNOS under HG conditions. Mechanistically, VAC-treated HMEC-1 cells exhibited higher AMPK phosphorylation, which was attenuated by HG stimulation. Moreover, HG-triggered miRNA-34a upregulation was inhibited by VAC pretreatment, which is in accordance with pretreatment with AMPK Inhibitor compound C (CC). In addition, both Reactive Oxygen Species (ROS) scavenger N-acetyl-L-cysteine (NAC) and VAC abolished HG-evoked dephosphorylation of AMPK and eNOS, increased miRNA-34a expression, and decreased NO production. These results suggest that VAC impedes HG-induced endothelial dysfunction via inhibition of the ROS/AMPK/miRNA-34a/eNOS signaling cascade.

Keywords

NO production; diabetic angiopathy; endothelial dysfunction; miRNA-34a.

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