Journal of Natural Medicines

, Volume 66, Issue 1, pp 149–157 | Cite as

Davallialactone protects against adriamycin-induced cardiotoxicity in vitro and in vivo

  • Sankarganesh Arunachalam
  • Sun Young Kim
  • Sun Hwa Lee
  • Young Hee Lee
  • Min Sun Kim
  • Bong Sik Yun
  • Ho Keun Yi
  • Pyoung Han Hwang
Original Paper

Abstract

Adriamycin (ADR) is a potent anticancer drug. Its clinical applications are limited due to its cardiotoxicity. Oxidative stress is responsible for cardiomyopathy induced by ADR. Previous studies have demonstrated that davallialactone (DAVA), extracted from mushroom Inonotus xeranticus, has potential antiplatelet aggregation activity and free radical scavenging properties. In this study, we investigated whether DAVA has protective effects against ADR-induced free radical accumulation and apoptosis in cardiac muscle cells and compared the effects of DAVA with N-acetylcysteine, a potent antioxidant. We evaluated the effect of DAVA on ADR-induced cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and crystal violet staining, the reactive oxygen species (ROS) production by flow cytometry, and the expression of stress-related proteins like Cu/Zn superoxide dismutase (SOD), Mn-SOD, and the involvement of mitogen-activated protein kinase pathway by Western blot analysis. Apoptosis was assessed by nuclear condensation and the expression levels of pro-apoptotic proteins, such as caspase-3 and polyadenosine diphosphate-ribose polymerase (PARP). The cardio-protective effects of DAVA were also evaluated in an in vivo study in an animal model of ADR-induced acute cardiomyopathy. Our results showed that DAVA significantly increased the viability of doxorubicin-injured H9c2 cells and inhibited ADR-induced ROS production, apoptosis, and the expression of Cu/Zn SOD and Mn-SOD. DAVA also inhibited the expression of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), which was activated by ADR. In the in vivo animal model, treatment involving DAVA significantly reduced cardiomyocyte lesions. These results suggest that DAVA is a potentially protective agent for ADR-induced cardiotoxicity in cardiomyocytes and can be a potential candidate to protect against cardiotoxicity in ADR-treated cancer patients.

Keywords

Davallialactone Adriamycin Cardiotoxicity Antioxidant effect 

Notes

Acknowledgments

The authors thank Professor S. Kamala-Kannan for the careful review of the manuscript and revision suggestions. This study was supported by a grant from the Korea Forest Service (S121010L090120) and in part by a grant of the Clinical Trial Center for Functional Foods of Chonbuk National University Hospital.

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Copyright information

© The Japanese Society of Pharmacognosy and Springer 2011

Authors and Affiliations

  • Sankarganesh Arunachalam
    • 1
    • 2
  • Sun Young Kim
    • 1
    • 2
  • Sun Hwa Lee
    • 3
  • Young Hee Lee
    • 4
  • Min Sun Kim
    • 1
  • Bong Sik Yun
    • 5
  • Ho Keun Yi
    • 4
  • Pyoung Han Hwang
    • 1
    • 2
  1. 1.Department of PediatricsChonbuk National University HospitalJeonjuRepublic of Korea
  2. 2.Research Institute of Clinical MedicineChonbuk National UniversityJeonjuRepublic of Korea
  3. 3.Division of Cardiology, Department of Internal Medicine, School of MedicineChonbuk National UniversityJeonjuRepublic of Korea
  4. 4.Department of Biochemistry, School of DentistryChonbuk National UniversityJeonjuRepublic of Korea
  5. 5.Division of Biotechnology, College of Environmental and Bioresources SciencesChonbuk National UniversityJeonjuRepublic of Korea

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