Compound Danshen Dripping Pills pretreatment protects the heart from ischemia/reperfusion injury by enhancing autophagic flux

Authors

  • Haiqiong Liu Department of Health Management, Zhujiang Hospital, Southern Medical University, China,Southern Medical University
  • Qian Liang Department of Cardiology of The First People’s Hospital of Foshan City, China
  • Xiheng Mei Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, China ,Department of Cardiology, Zhujiang Hospital of Southern Medical University, China
  • Hekai Li Li Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, China
  • Jing Yan Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, China,Department of Cardiology, Zhujiang Hospital of Southern Medical University, China
  • Man Long Ultrasound Medical Center, Zhujiang Hospital of Southern Medical University, China
  • Xili Yang Department of Cardiology of The First People’s Hospital of Foshan City, China
  • Wei Wang Department of Cardiology of The First People’s Hospital of Foshan City, China
  • Weijie Li Department of Cardiology of The First People’s Hospital of Foshan City, China
  • Aihua Chen Department of Health Management, Zhujiang Hospital, Southern Medical University, China http://orcid.org/0000-0002-7682-4255
  • Yuanna Ling Department of Nuclear Medicine of Zhujiang Hospital of Southern Medical University, China http://orcid.org/0000-0002-2282-0718

Keywords:

ischemia/reperfusion;, Compound Danshen Dripping Pills;, Autophagy;, Apoptosis

Abstract

Compound Danshen Dripping Pills (CDDPs) have been used in clinical treatment to protect the heart from ischemia/reperfusion (IR) injury for many years. However, the underlying mechanism implicated in the protective effects remains to be explored. Here, we determined the effects of CDDPs in Sprague-Dawley rats with the IR model. Cardiac function in vivo was assessed by echocardiography. Transmission electron microscopy, histological and immunohistochemical techniques, Western blotting and recombinant adeno-associated virus 9 transfection were used to illustrate the effects of CDDPs on IR and autophagy. Our results showed that pretreatment with CDDPs decreased the level of serum myocardial enzymes and infarct size in rats after IR. Apoptosis evaluation showed that CDDPs significantly ameliorated the cardiac apoptosis level after IR. Meanwhile, CDDPs pretreatment increased myocardial autophagic flux, with upregulation of LC3B, downregulation of p62, and increased autophagosomes and autolysosomes. Moreover, the autophagic flux inhibitor chloroquine could increase IR injury, while CDDPs could partially reverse the effects. Furthermore, our results showed that the activation of AMPK/mTOR was involved in the cardioprotective effect exerted by CDDPs. Herein, we suggest that CDDPs partially protect the heart from IR injury by enhancing autophagic flux through the activation of AMPK/mTOR.

Downloads

Download data is not yet available.

Author Biographies

  • Haiqiong Liu, Department of Health Management, Zhujiang Hospital, Southern Medical University, China,Southern Medical University
    writing-original Draft investigation revising manuscript  Haiqiong Liu and Qian Liang contributed equally to this article.
  • Qian Liang, Department of Cardiology of The First People’s Hospital of Foshan City, China
    conceptualization methodology Haiqiong Liu and Qian Liang contributed equally to this article.
  • Xiheng Mei, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, China ,Department of Cardiology, Zhujiang Hospital of Southern Medical University, China
    software validation
  • Hekai Li Li, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, China

    resources

  • Jing Yan, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, China,Department of Cardiology, Zhujiang Hospital of Southern Medical University, China

    resources

  • Man Long, Ultrasound Medical Center, Zhujiang Hospital of Southern Medical University, China

    resources

  • Xili Yang, Department of Cardiology of The First People’s Hospital of Foshan City, China
    formal analysis
  • Wei Wang, Department of Cardiology of The First People’s Hospital of Foshan City, China
    visualization
  • Weijie Li, Department of Cardiology of The First People’s Hospital of Foshan City, China
    data curation
  • Aihua Chen, Department of Health Management, Zhujiang Hospital, Southern Medical University, China

    Supervision

  • Yuanna Ling, Department of Nuclear Medicine of Zhujiang Hospital of Southern Medical University, China
    project administration writing-review & editing

References

Chu Y, Zhang L, Wang X, Guo J, Guo Z, Ma X. The Effect of Compound Danshen Dripping Pills, a Chinese Herb Medicine, On the Pharmacokinetics and Pharmacodynamics of Warfarin in Rats. J Ethnopharmacol. 2011;137(3):1457-1461.

Denton D, Nicolson S, Kumar S. Cell Death by Autophagy: Facts and Apparent Artefacts. Cell Death Differ. 2012;2012-01-01;19(1):87-95.

Gatica D, Chiong M, Lavandero S, Klionsky DJ. Molecular Mechanisms of Autophagy in the Cardiovascular System. Circ Res. 2015;2015-01-30;116(3):456-467.

Ghavami S, Gupta S, Ambrose E, Hnatowich M, Freed DH, Dixon IM. Autophagy and Heart Disease: Implications for Cardiac Ischemia-Reperfusion Damage. Curr Mol Med. 2014;2014-01-20;14(5):616-629.

Giampieri F, Afrin S, Forbes-Hernandez TY, Gasparrini M, Cianciosi D, Reboredo-Rodriguez P, et al. Autophagy in Human Health and Disease: Novel Therapeutic Opportunities. Antioxid Redox Signal. 2018;2018-08-10.

Guo J, Yong Y, Aa J, Cao B, Sun R, Yu X, et al. Compound Danshen Dripping Pills Modulate the Perturbed Energy Metabolism in a Rat Model of Acute Myocardial Ischemia. Sci Rep-Uk. 2016;6(1).

Huang J, Sun Y, Chen L, Ma G. The Lymphocyte Adapter Protein: A Negative Regulator of Myocardial Ischemia/Reperfusion Injury. J Mol Cell Cardiol. 2019;134:107-118.

Li Y, Wang S, Liu B, Tang L, Kuang R, Wang X, et al. Sulforaphane prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating SIRT1 and subsequently inhibiting ER stress. Acta Pharmacol Sin. 2016;37(3):344-353.

Ling Y, Chen G, Deng Y, Tang H, Ling L, Zhou X, et al. Polydatin Post-Treatment Alleviates Myocardial Ischaemia/Reperfusion Injury by Promoting Autophagic Flux. Clin Sci. 2016;2016-08-08;130(18):1641-1653.

Marek-Iannucci S, Thomas A, Hou J, Crupi A, Sin J, Taylor DJ, et al. Myocardial Hypothermia Increases Autophagic Flux, Mitochondrial Mass and Myocardial Function After Ischemia-Reperfusion Injury. Sci Rep-Uk. 2019;9(1).

Murphy E, Steenbergen C. Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury. Physiol Rev. 2008;88(2):581-609.

Qi D, Young LH. AMPK: Energy Sensor and Survival Mechanism in the Ischemic Heart. Trends Endocrinol Metab. 2015;2015-08-01;26(8):422-429.

Ren-an Q, Juan L, Chuyuan L, Wenjuan F, Chunyan H, Xuemei Y, et al. Study of the Protective Mechanisms of Compound Danshen Tablet (Fufang Danshen Pian) Against Myocardial Ischemia/Reperfusion Injury Via the Akt-eNOS Signaling Pathway in Rats. J Ethnopharmacol. 2014;156:190-198.

Sciarretta S, Hariharan N, Monden Y, Zablocki D, Sadoshima J. Is Autophagy in Response to Ischemia and Reperfusion Protective or Detrimental for the Heart? Pediatr Cardiol. 2011;32(3):275-281.

Tan Z, Liu H, Song X, Ling Y, He S, Yan Y, et al. Honokiol Post-Treatment Ameliorates Myocardial Ischemia/Reperfusion Injury by Enhancing Autophagic Flux and Reducing Intracellular ROS Production. Chem-Biol Interact. 2019;307:82-90.

Tang H, Song X, Ling Y, Wang X, Yang P, Luo T, et al. Puerarin Attenuates Myocardial Hypoxia Reoxygenation Injury by Inhibiting Autophagy Via the Akt Signaling Pathway. Mol Med Rep. 2017 2017-06-01;15(6):3747-3754.

Tang L, Mo Y, Li Y, Zhong Y, He S, Zhang Y, et al. Urolithin a Alleviates Myocardial Ischemia/Reperfusion Injury Via PI3K/Akt Pathway. Biochem Biophys Res Commun. 2017;2017-05-06;486(3):774-780.

Yan J, Yan JY, Wang YX, Ling YN, Song XD, Wang SY, et al. Spermidine‐Enhanced Autophagic Flux Improves Cardiac Dysfunction Following Myocardial Infarction by Targeting the AMPK/mTOR Signalling Pathway. Brit J Pharmacol. 2019;2019-07-17.

Zhang Y, Ling Y, Yang L, Cheng Y, Yang P, Song X, et al. Liraglutide Relieves Myocardial Damage by Promoting Autophagy Via AMPK-mTOR Signaling Pathway in Zucker Diabetic Fatty Rat. Mol Cell Endocrinol. 2017;2017-06-15;448:98-107.

Zhao N, Liu Y, Wang F, Hu B, Sun K, Chang X, et al. Cardiotonic Pills, a Compound Chinese Medicine, Protects Ischemia-Reperfusion-Induced Microcirculatory Disturbance and Myocardial Damage in Rats. Am J Physiol-Heart C. 2010a;298(4):H1166-H1176.

Zhao N, Liu Y, Wang F, Hu B, Sun K, Chang X, et al. Cardiotonic Pills, a Compound Chinese Medicine, Protects Ischemia-Reperfusion-Induced Microcirculatory Disturbance and Myocardial Damage in Rats. Am J Physiol-Heart C. 2010b;298(4):H1166-H1176.

Zheng Y, Gu S, Li X, Tan J, Liu S, Jiang Y, et al. Berbamine Postconditioning Protects the Heart From Ischemia/Reperfusion Injury through Modulation of Autophagy. Cell Death Dis. 2017;8(2):e2577.

Zhong Y, Zhong P, He S, Zhang Y, Tang L, Ling Y, et al. Trimetazidine Protects Cardiomyocytes Against Hypoxia/Reoxygenation Injury by Promoting AMP-activated Protein Kinase-Dependent Autophagic Flux. J Cardiovasc Pharmacol. 2017;2017-06-01;69(6):389-397.

Zhou W, Yuan W, Chen C, Wang S, Liang S. Study on material base and action mechanism of compound danshen dripping pills for treatment of atherosclerosis based on modularity analysis. J Ethnopharmacol. 2016;193:36-44.

Downloads

Published

2023-09-08

Issue

Vol. 59 (2023)

Section

Article

License

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.

The on line journal has open and free access.

How to Cite

Compound Danshen Dripping Pills pretreatment protects the heart from ischemia/reperfusion injury by enhancing autophagic flux . (2023). Brazilian Journal of Pharmaceutical Sciences, 59, 14. https://revistas.usp.br/bjps/article/view/222559

Funding data