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San-Huang-Xie-Xin-Tang protects cardiomyocytes against hypoxia/reoxygenation injury via inhibition of oxidative stress-induced apoptosis

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Abstract

Oxidative stress has been widely implicated in the pathogenesis of hypoxia/reoxygenation (H/R) injury. San-Huang-Xie-Xin-Tang (SHXT), a widely used traditional Chinese medication, has been shown to possess antioxidant effects. Here, we investigated whether SHXT and its main component baicalin can attenuate oxidative stress induced by H/R injury. H9c2 rat ventricular cells were exposed to SHXT or baicalin followed by hypoxia for 24 h and/or reoxygenation for 8 h. Pretreatment with SHXT and baicalin both significantly prevented cell death and production of reactive oxygen species induced by hypoxia or H/R in H9c2 cardiomyoctes. In addition, SHXT and baicalin also inhibited hypoxia- or H/R-induced apoptosis, with associated decreased Bax protein, increased Bcl-2 protein, and decreased caspase-3 activity. Furthermore, we found that hypoxia and H/R decreased endothelial nitric oxide synthase (eNOS) expression and nitrite production, and these effects were counteracted by SHXT and baicalein. Finally, SHXT inhibited H/R-induced activation of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation in H9c2 rat ventricular cells. The present study demonstrates for the first time that SHXT can protect cardiomyocytes from H/R injury via inhibition of oxidative stress-induced apoptosis. These cardioprotective effects are possibly mediated through eNOS enhancement and p38 MAPK and JNK-dependent signaling pathways.

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Acknowledgments

We would like to thank Ms. Li-Ying Chen for technical assistance. This work was supported by Grant CCMP96-RD-014 to Dr. Jwu-Lai Yeh from the Committee on Chinese Medicine and Pharmacy, Department of Health, Taiwan.

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Authors and Affiliations

  1. Department of Pharmacy, Chia-Nan University of Pharmacy and Science, 60 Erh-Jen Road, Section 1, Pao-Ann, Jen-Te, Tainan, 717, Taiwan

    Shu-Fen Liou

  2. Department of Paediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan

    Jong-Hau Hsu & Jiunn-Ren Wu

  3. Graduate Institute of Engineering, National Taiwan University of Science and Technology, 1, Sec. 3, Chung-hsiao E. Rd., Taipei, 10608, Taiwan

    Jyh-Chong Liang

  4. Department and Graduate Institute of Pharmacology, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan

    Hung-Jen Ke, Ing-Jun Chen & Jwu-Lai Yeh

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  1. Shu-Fen Liou
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  2. Jong-Hau Hsu
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Correspondence to Jwu-Lai Yeh.

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Liou, SF., Hsu, JH., Liang, JC. et al. San-Huang-Xie-Xin-Tang protects cardiomyocytes against hypoxia/reoxygenation injury via inhibition of oxidative stress-induced apoptosis. J Nat Med 66, 311–320 (2012). https://doi.org/10.1007/s11418-011-0592-0

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  • DOI: https://doi.org/10.1007/s11418-011-0592-0

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