title: Ginsenoside Rg3 antagonizes adriamycin-induced cardiotoxicity by improving endothelial dysfunction from oxidative stress via upregulating the Nrf2-ARE pathway through the activation of akt.
abstract: BACKGROUND
  Adriamycin (ADM) is an antineoplastic agent that is effective against a wide range of cancers, but cardiac toxicity limits its clinical application. Ginsenoside Rg3 (Rg3), an anti-cancer active ingredient of Panax ginseng, was reported to have anti-oxidative, anti-apoptotic, and cardioprotective properties.
  
  
  OBJECTIVE
  The current study aimed to investigate the possible protective effect of Rg3 against ADM-induced cardiotoxicity.
  
  
  METHODS
  The activity of Rg3 to improve endothelial dysfunction was processed both in vivo and in vitro.
  
  
  METHODS
  We investigated the cardioprotective effect of Rg3 on ADM treated rats by echocardiography. The endothelial dysfunction was assessed using an aortic ring assay. Cardiac microvascular endothelial cells were cultured to investigate the effects of Rg3 on ADM-treated cells.
  
  
  RESULTS
  Results showed that Rg3 could ameliorate the decrease in the ejection fraction and fractional shortening that was induced by ADM, and improve the left ventricular outflow. The aortic ring assay showed that Rg3 could partially recover the abnormal vascular function. In vitro studies showed that Rg3 could promote cell viability to attenuate ADM induced oxidative damage and apoptosis. This counteraction was achieved partially via activation of the Nrf2-ARE pathway through the activation of Akt.
  
  
  CONCLUSIONS
  These findings elucidated the potential of Rg3 as a promising reagent for treating ADM-induced cardiotoxicity in clinic.
authors: College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors: Xiaoying
authors: X
authors: Wang
authors: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors: Lili
authors: L
authors: Chen
authors: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors: Ting
authors: T
authors: Wang
authors: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors: Xiaoqing
authors: X
authors: Jiang
authors: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors: Han
authors: H
authors: Zhang
authors: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors: Pan
authors: P
authors: Li
authors: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors: Bin
authors: B
authors: Lv
authors: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. Electronic address: gaoxiumei@tjutcm.edu.cn.
authors: Xiumei
authors: X
authors: Gao
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects; D020013:Calcium Signaling; D002316:Cardiotonic Agents / Q000494:pharmacology*; D066126:Cardiotoxicity / Q000188:drug therapy*; D002478:Cells, Cultured; D004317:Doxorubicin / Q000009:adverse effects*; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D036145:Ginsenosides / Q000494:pharmacology*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D005894:Panax / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D016277:Ventricular Function, Left
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002316:Cardiotonic Agents; D036145:Ginsenosides; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; C097367:ginsenoside Rg3; D004317:Doxorubicin; D051057:Proto-Oncogene Proteins c-akt
keywords: Adriamycin; Aortic ring; Cardiotoxicity; Ginsenoside Rg3; Nrf2; Oxidative stress