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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2012, Vol. 17 ›› Issue (7): 736-743.

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Protective effect of 23-hydroxybetulinic acid against doxorubicin-induced cardiotoxicity through the antioxidant activity in H9c2 cells

HAO Gang1, ZHOU Fang1, LIU Jia-li1, WANG Guang-ji1, SANG Guo-wei2, YE Wen-cai3   

  1. 1Key Laboratory of Drug Metabolism and Pharmacokinetics, Nanjing 210009, Jiangsu, China;
    2National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, China;
    3Institute of Traditional Chinese Medicine and Nature Products, Jinan University, Guangzhou 510632, Guangdong, China
  • Received:2012-03-20 Revised:2012-05-25 Published:2012-07-17

Abstract: AIM: To investigate the potential protective effects of 23-hydroxybetulinic acid (23-HBA) on doxorubicin (DOX)-induced cardiotoxicity and the underlying mechanisms. METHODS: H9c2 cells were treated with DOX, 23-HBA, or their combinations, cell size and protein content were determined to evaluate the cardiac hypertrophy induced by DOX. Expression of ANP and BNP mRNA were studied by Real-time PCR. DOX-induced caspase-3 activation and apoptosis were further studied. Oxidative stress and lipid peroxidation were determined to evaluate the potential mechanism of the cardioprotective effect of 23-HBA. RESULTS: 23-HBA remarkably reduced the mRNA level of ANP and BNP induced by DOX, and reversed the cardiac hypertrophy caused by DOX treatment. Caspase-3 activity also significantly reduced when combined treated with 23-HBA and DOX compared to DOX treatment. Further studies showed that 23-HBA exerted its cardioprotective effect on DOX through decreasing the intracellular ROS and MDA amount. CONCLUSION: 23-HBA protected H9c2 cells against the cardiotoxicity of DOX, and the reduction of oxygen free radicals in cardiac myocytes may be the underlying mechanism mediating the protective effect of 23-HBA.

Key words: 23-HBA, Doxorubicin, Cardiotoxicity

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