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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 970490, 14 pages
Research Article

Higenamine Combined with [6]-Gingerol Suppresses Doxorubicin-Triggered Oxidative Stress and Apoptosis in Cardiomyocytes via Upregulation of PI3K/Akt Pathway

1Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road, Guangzhou 510080, China
2Institute of Integrated Traditional Chinese and Western Medicine, Sun Yat-Sen University, Guangzhou 510080, China
3Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China

Received 26 March 2013; Accepted 10 May 2013

Academic Editor: Bashar Saad

Copyright © 2013 Yan-Ling Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Sini decoction is a well-known formula of traditional Chinese medicine, which has been used to treat cardiovascular disease for many years. Previously, we demonstrated that Sini decoction prevented doxorubicin-induced heart failure in vivo. However, its active components are still unclear. Thus, we investigated the active components of Sini decoction and their cardioprotective mechanisms in the in vitro neonatal rat cardiomyocytes and H9c2 cell line models of doxorubicin-induced cytotoxicity. Our results demonstrated that treatment with higenamine or [6]-gingerol increased viability of doxorubicine-injured cardiomyocytes. Moreover, combined use of higenamine and [6]-gingerol exerted more profound protective effects than either drug as a single agent, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. In addition, we found that treatment with doxorubicin reduced SOD activity, increased ROS generation, enhanced MDA formation, induced release of LDH, and triggered the intrinsic mitochondria-dependent apoptotic pathway in cardiomyocytes, which was inhibited by cotreatment of higenamine and [6]-gingerol. Most importantly, the cytoprotection of higenamine plus [6]-gingerol could be abrogated by LY294002, a PI3K inhibitor. In conclusion, combination of higenamine and [6]-gingerol exerts cardioprotective effect against doxorubicin-induced cardiotoxicity through activating the PI3K/Akt signaling pathway. Higenamine and [6]-gingerol may be the active components of Sini decoction.