LongShengZhi capsule inhibits doxorubicin-induced heart failure by anti-oxidative stress

  • Biomed Pharmacother. 2020 Mar;123:109803. doi: 10.1016/j.biopha.2019.109803.
Shuai Xu  1 ,  Yuanyu Wang  1 ,  Maoyun Yu  2 ,  Dandan Wang  1 ,  Yingquan Liang  1 ,  Yuanli Chen  1 ,  Chenzhong Liao  1 ,  Zhouling Xie  1 ,  Buchang Zhao  3 ,  Jihong Han  4 ,  Yajun Duan  1 ,  Xiaoxiao Yang  5
Affiliations
  • 1. Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • 2. School of Biological and Pharmaceutical Engineering, West Anhui University, Lu'an, China.
  • 3. Buchang Pharmaceutical Co. Ltd., Xi'an, China.
  • 4. Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China; College of Life Science, Key Laboratory of Bioactive Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
  • 5. Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China. Electronic address: [email protected].
PMID: 31877550 DOI: 10.1016/j.biopha.2019.109803
Abstract

Heart failure is a major cause of morbidity and mortality worldwide. LongShengZhi capsule (LSZ), a traditional Chinese medicine, is used for treatment of patients with vascular diseases. Herein we investigated the effect of LSZ treatment on doxorubicin (DOX)-induced heart failure in mice. C57BL/6 mice randomly in 3 groups received following treatment: Control group, mice were fed normal chow; DOX group, mice were intraperitoneally injected DOX to induce heart failure and fed normal chow; and LSZ group, mice were injected DOX and fed normal chow containing LSZ. DOX induced heart failure as evidenced by increased serum Creatine Kinase, lactic dehydrogenase and α-hydroxybutyrate dehydrogenase, and cardiac fibrosis. However, LSZ treatment substantially inhibited DOX-induced heart failure parameters. Mechanistically, LSZ reduced Collagen content and fibrosis by inhibiting expression of Collagen type I α1 (COL1α1), COL1α2, α-smooth muscle actin and transforming growth factor β1. In addition, DOX-induced cell Apoptosis was inhibited by LSZ, coupled with reduced Caspase 3 activity and mRNA expression. LSZ decreased inflammatory cytokine levels. More importantly, LSZ decreased oxidative stress by inducing expression of anti-oxidative stress Enzymes including superoxide dismutase 1 (SOD1), SOD2, catalase and Glutathione Peroxidase 1 through activation of forkhead box O3A and Sirtuin 3. In conclusion, our study demonstrates that LSZ reduces heart failure by reducing production of Reactive Oxygen Species and inhibiting inflammation/Apoptosis. Our study also suggests the potential application of LSZ for heart failure treatment.

Keywords
Doxorubicin; Fibrosis; Heart failure; LongShengZhi capsule; Oxidative stress.
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