Cardiovascular Toxicology

, Volume 16, Issue 2, pp 101–110 | Cite as

Protection of Luteolin-7-O-Glucoside Against Doxorubicin-Induced Injury Through PTEN/Akt and ERK Pathway in H9c2 Cells

  • Hong Yao
  • Zhimei Shang
  • Penghong Wang
  • Shuixian Li
  • Qianyun Zhang
  • Huiqin Tian
  • Dongmei Ren
  • Xiuzhen Han


Luteolin-7-O-glucoside (LUTG) was isolated from the plants of Dracocephalum tanguticum Maxim. Previous research has showed that LUTG pretreatment had a significant protective effect against doxorubicin (DOX)-induced cardiotoxicity by reducing intracellular calcium overload and leakage of creatine kinase and lactate dehydrogenase. But the underlying mechanisms have not been completely elucidated. In the present study, we investigated the effects of LUTG on H9c2 cell morphology, viability, apoptosis, reactive oxygen species generation, and the mitochondrial transmembrane potentials. The expression of p-PTEN, p-Akt, p-ERK, p-mTOR, and p-GSK-3β were detected by Western blotting. Compared with DOX alone treatment group, the morphological injury and apoptosis of the cells in groups treated by DOX plus LUTG were alleviated, cell viability was increased, ROS generation was lowered remarkably, and mitochondrial depolarization was mitigated. In DOX group, the expression of p-PTEN was lower than normal group and the expression of p-Akt and p-ERK was higher than normal group. In the groups treated with LUTG (20 μM), the expression of p-PTEN was upregulated and the expression of p-Akt, p-ERK, p-mTOR, and p-GSK-3β was downregulated. These results indicated that the protective effects of LUTG against DOX-induced cardiotoxicity may be related to anti-apoptosis through PTEN/Akt and ERK pathway.


Luteolin-7-O-glucoside Doxorubicin PTEN Akt ERK 



This work was supported by Grants from the Natural Science Foundation of Shandong Province (No. ZR2013HM084) and Independent Innovation Foundation of Shandong University (No. 2012ZD043) of P.R.China.

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Hong Yao
    • 1
  • Zhimei Shang
    • 2
  • Penghong Wang
    • 1
  • Shuixian Li
    • 1
  • Qianyun Zhang
    • 1
  • Huiqin Tian
    • 1
  • Dongmei Ren
    • 3
  • Xiuzhen Han
    • 1
  1. 1.Department of Pharmacology, School of Pharmaceutical SciencesShandong UniversityJinanChina
  2. 2.Department of OncologyWei Fang Traditional Chinese HospitalWeifangChina
  3. 3.Department of Natural Product Chemistry, School of Pharmaceutical SciencesShandong UniversityJinanChina

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