Research Papers: Gerotarget (Focus on Aging):

Activation of Nrf2-mediated anti-oxidant genes by antrodin C prevents hyperglycemia-induced senescence and apoptosis in human endothelial cells

Kumar K.J. Senthil _, Vani M. Gokila and Sheng-Yang Wang

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Oncotarget. 2017; 8:96568-96587. https://doi.org/10.18632/oncotarget.19951

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Kumar K.J. Senthil1, Vani M. Gokila1,2 and Sheng-Yang Wang1,2,3

1 Department of Forestry, National Chung Hsing University, Taichung, Taiwan

2 National Chung Hsing University/University of California at Davis, Plant and Food Biotechnology Center, National Chung Hsing University, Taichung, Taiwan

3 Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan

Correspondence to:

Sheng-Yang Wang, email:

Keywords: antrodin C, Antrodia cinnamomea, high glucose, endothelial cells, senescence, Gerotarget

Received: June 21, 2017 Accepted: July 25, 2017 Published: August 04, 2017


In the present study, we investigated the effects of antrodin C (ADC), a maleimide derivative isolated from mycelia of Antrodia cinnamomea, on high glucose (HG, 30 mM)-accelerated endothelial dysfunction in vitro. HG-induced cytotoxicity in human umbilical vein endothelial cells (HUVECs) was significantly ameliorated by ADC. In addition, treatment with ADC significantly prevented HG-induced senescence, growth arrest at the G1-S transition phase and apoptosis in HUVECs. Moreover, the increased level of intracellular reactive oxygen species (ROS) under HG condition was significantly ameliorated by ADC. Further analysis revealed that ADC-mediated anti-oxidant effects were due to up-regulation of cellular anti-oxidant genes, such as HO-1 and NQO-1 via promotion of the transcriptional activity of Nrf2, which was further confirmed by the failure of ADC to protect HUVECs from HG-induced dysfunction under HO-1 inhibition or Nrf2 silencing. Furthermore, hyperosmotic glucose (HOG, 60 mM)-induced uncontrolled production of ROS, rapid apoptotic cell death and HUVEC injury were significantly prevented by ADC, whereas these preventive effects were barely observed in HO-1 inhibited or Nrf2 silenced cells. Taken together, these results suggest that ADC may represent a promising intervention in diabetic-associated cardiovascular diseases by activating the Nrf2-dependent cellular anti-oxidant defense system.

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