Skip to main content

Advertisement

SpringerLink
Log in

Anti-inflammatory Effect of Protocatechuic Aldehyde on Myocardial Ischemia/Reperfusion Injury In Vivo and In Vitro

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response plays a vital role, is frequently encountered in clinical practice. The present study was aimed to investigate the anti-inflammatory effect and the possible mechanism of protocatechuic aldehyde (PAl) on MI/R injury both in vivo and in vitro. The rat model of MI/R injury was induced by ligation of the left anterior descending coronary artery for 30 min, followed by 3-h reperfusion, and pretreatment with PAl could protect the heart from MI/R injury by reducing myocardial infarct size and the activities of creatine kinase-MB and cardiac troponin I (cTn-I) in serum. Also, PAl administration markedly reduced cellular injury induced by simulated ischemia/reperfusion (SI/R) in cultured neonatal rat cardiomyocytes, which was evidenced by increased cell viability, reduced lactate dehydrogenase and cTn-I activities in the culture medium, and greatly decreased percentage of cell apoptosis. Moreover, the levels of tumor necrosis factor-α, interleukin-6, intracellular adhesion molecule-1, phosphorylated IκB-α, and the nuclear translocation of nuclear factor-kappa B (NF-κB) were all evidently decreased by PAl both in vivo and in vitro. Taken together, these observations suggested that PAl could exert great protective effects against MI/R injury in rats and SI/R injury in cultured neonatal rat cardiomyocytes, and the cardioprotective mechanism might be involved in the suppression of inflammatory response via inhibiting the NF-κB signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Yellon, D.M., and D.J. Hausenloy. 2007. Myocardial reperfusion injury. The New England Journal o f Medicine 357: 1121–1135.

    Article  CAS  Google Scholar 

  2. Frangogiannis, N.G., C.W. Smith, and M.L. Entman. 2002. The inflammatory response in myocardial infarction. Cardiovascular Research 53: 31–47.

    Article  PubMed  CAS  Google Scholar 

  3. Nah, D.Y., and M.Y. Rhee. 2009. The inflammatory response and cardiac repair after myocardial infarction. Korean Circulation Journal 39: 393–398.

    Article  PubMed  CAS  Google Scholar 

  4. Frangogiannis, N.G., M.L. Lindsey, L.H. Michael, K.A. Youker, R.B. Bressler, L.H. Mendoza, R.N. Spengler, C.W. Smith, and M.L. Entman. 1998. Resident cardiac mast cells degranulate and release preformed TNF-a, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation 98: 699–710.

    Article  PubMed  CAS  Google Scholar 

  5. Ke, J.J., F.X. Yu, Y. Rao, and Y.L. Wang. 2011. Adenosine postconditioning protects against myocardial ischemia–reperfusion injury though modulate production of TNF-a and prevents activation of transcription factor NF-kappaB. Molecular Biology Reports 38: 531–538.

    Article  PubMed  CAS  Google Scholar 

  6. Kukielka, G.L., H.K. Hawkins, L. Michael, A.M. Manninget, K. Youker, C. Lane, M.L. Entman, C.W. Smith, and D.C. Anderson. 1993. Regulation of intercellular adhesion molecule-1 (ICAM-1) in ischemic and reperfused canine myocardium. The Journal of Clinical Investigation 92: 1504–1516.

    Article  PubMed  CAS  Google Scholar 

  7. Gurevitch, J., I. Frolkis, Y. Yuhas, B. Lifschitz-Mercer, E. Berger, Y. Paz, M. Masta, A. Kramer, and P. Mohr. 1997. Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion. Journal of the American College of Cardiology 30: 1554–1561.

    Article  PubMed  CAS  Google Scholar 

  8. Onai, Y., J.I. Suzuki, T. Kakuta, Y. Maejima, G. Haraguchi, H. Fukasawa, S. Muto, A. Itai, and M. Isobe. 2004. Inhibition of IκB phosphorylation in cardiomyocytes attenuates myocardial ischemia/reperfusion injury. Cardiovascular Research 63: 51–59.

    Article  PubMed  CAS  Google Scholar 

  9. Braunersreuthera, V., C. Pellieuxa, G. Pellia, F. Burger, S. Steffens, C. Montessuit, C. Weber, A. Proudfoot, F. Mach, and C. Arnaud. 2010. Chemokine CCL5/RANTES inhibition reduces myocardial reperfusion injury in atherosclerotic mice. Journal of Molecular and Cellular Cardiology 48: 789–798.

    Article  Google Scholar 

  10. Yuan, Z.F., G.X. Fan, B.B. Wang, Z.Y. He, and P.Q. Shu. 2008. Myocardial protective effect of Danshen injection in patients undergoing open heart surgery. Journal of Clinical Medicine in Practice 12: 12–14.

    Google Scholar 

  11. Zhou, R., L.F. He, Y.J. Li, Y. Shen, R.B. Chao, and J.R. Du. 2012. Cardioprotective effect of water and ethanol extract of Salvia miltiorrhiza in an experimental model of myocardial infarction. Journal of Ethnopharmacology 139: 440–446.

    Article  PubMed  Google Scholar 

  12. Qiao, Z.Y., J.W. Ma, and H.J. Liu. 2011. Evaluation of the antioxidant potential of Salvia miltiorrhiza ethanol extract in a rat model of ischemia–reperfusion injury. Molecules 16: 10002–10012.

    Article  PubMed  CAS  Google Scholar 

  13. Zhou, Z., Y. Liu, A.D. Miao, and S.Q. Wang. 2005. Protocatechuic aldehyde suppresses TNF-a-induced ICAM-1 and VCAM-1 expression in human umbilical vein endothelial cells. European Journal of Pharmacology 513: 1–8.

    Article  PubMed  CAS  Google Scholar 

  14. Han, C.J., R. Lin, J.T. Liu, Y. Liu, and H. Zhang. 2007. Protection of vascular endothelial cells from ox-LDL induced injury by protocatechualdehyde. Journal of Chinese Medicinal Materials 30: 1541–1544.

    PubMed  CAS  Google Scholar 

  15. Frantz, S., J. Tillmanns, P.J. Kuhlencordt, I. Schmidt, A. Adamek, C. Dienesch, T. Thum, S. Gerondakis, G. Ertl, and J. Bauersachs. 2007. Tissue-specific effects of the nuclear factor κB subunit p50 on myocardial ischemia–reperfusion injury. The American Journal of Pathology 171: 507–512.

    Article  PubMed  CAS  Google Scholar 

  16. Zhu, J., Y. Qiu, Q. Wang, Y. Zhu, S. Hu, L. Zheng, L. Wang, and Y. Zhang. 2008. Low dose cyclophosphamide rescues myocardial function from ischemia–reperfusion in rats. European Journal of Cardio-Thoracic Surgery 34: 661–666.

    Article  PubMed  Google Scholar 

  17. Zhang, J.Y., Z.W. Chen, and H. Yao. 2012. Protective effect of urantide against ischemia–reperfusion injury via protein kinase C and phosphtidylinositol 3′-kinase–Akt pathway. Canadian Journal of Physiology and Pharmacology 90: 637–645.

    Article  PubMed  CAS  Google Scholar 

  18. Ren, Z.H., Y.H. Tong, W. Xu, J. Ma, and Y. Chen. 2010. Tanshinone II A attenuates inflammatory responses of rats with myocardial infarction by reducing MCP-1 expression. Phytomedicine 17: 212–218.

    Article  PubMed  CAS  Google Scholar 

  19. Li, J., H.F. Zhang, F. Wu, Y. Nan, H. Ma, W.Y. Guo, H.C. Wang, J. Ren, U.N. Das, and F. Gao. 2008. Insulin inhibits tumor necrosis factor-α induction in myocardial ischemia/reperfusion: role of Akt and endothelial nitric oxide synthase phosphorylation. Critical Care Medicine 36: 1551–1558.

    Article  PubMed  CAS  Google Scholar 

  20. Cao, C.M., Y. Zhang, N. Weisleder, C. Ferrante, X.H. Wang, J.J. Ma, and R.P. Xiao. 2010. MG53 constitutes a primary determinant of cardiac ischemic preconditioning. Circulation 121: 2565–2574.

    Article  PubMed  CAS  Google Scholar 

  21. Etievent, J.P., S. Chocron, G. Toubin, C. Taberlet, K. Alwan, F. Clement, A. Cordier, N. Schipman, and J.P. Kantelip. 1995. Use of cardiac troponin I as a marker of perioperative myocardial ischemia. The Annals of Thoracic Surgery 59: 1192–1194.

    Article  PubMed  CAS  Google Scholar 

  22. Lin, L., X.D. Wu, A.K. Davey, and J.P. Wang. 2010. The anti-inflammatory effect of Baicalin on hypoxia/reoxygenation and TNF-α induced injury in cultural rat cardiomyocytes. Phytotherapy Research 24: 429–437.

    Article  PubMed  CAS  Google Scholar 

  23. Freude, B., T.N. Masters, F. Robicsek, A. Fokin, S. Kostin, R. Zimmermann, C. Ullmann, S. Lorenz-Meyer, and J. Schaper. 2000. Apoptosis is initiated by myocardial ischemia and executed during reperfusion. Journal of Molecular and Cellular Cardiology 32: 197–208.

    Article  PubMed  CAS  Google Scholar 

  24. Gwechenberger, M., L.H. Mendoza, K.A. Youker, N.G. Frangogiannis, C.W. Smith, L.H. Michaelet, and M.L. Entman. 1999. Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions. Circulation 99: 546–551.

    Article  PubMed  CAS  Google Scholar 

  25. Kacimi, R., J.S. Karliner, F. Koudssi, and C.S. Long. 1998. Expression and regulation of adhesion molecules in cardiac cells by cytokines: response to acute hypoxia. Circulation Research 82: 576–586.

    Article  PubMed  CAS  Google Scholar 

  26. Kukielka, G.L., C.W. Smith, A.M. Manning, K.A. Youkeret, L.H. Michael, and M.L. Entman. 1995. Induction of interleukin-6 synthesis in the myocardium potential role in postreperfusion inflammatory injury. Circulation 92: 1866–1875.

    Article  PubMed  CAS  Google Scholar 

  27. Smith, C.W., M.L. Entman, C.L. Lane, A.L. Beaudet, T.L. Ty, K. Youker, H.K. Hawkins, and D.C. Anderson. 1991. Adherence of neutrophils to canine cardiac myocytes in vitro is dependent on intercellular adhesion molecule-1. The Journal of Clinical Investigation 88: 1216–1223.

    Article  PubMed  CAS  Google Scholar 

  28. Vinten-Johansen, J. 2004. Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury. Cardiovascular Research 61: 481–497.

    Article  PubMed  CAS  Google Scholar 

  29. Jones, W.K., M. Brown, M. Wilhide, S.W. He, and X.P. Ren. 2005. NF-κB in cardiovascular disease: diverse and specific effects of a “general” transcription factor? Cardiovascular Toxicology 05: 183–201.

    Article  CAS  Google Scholar 

  30. Kim, J.W., Y.C. Jin, Y.M. Kim, S. Rhie, H.J. Kim, H.G. Seo, J.H. Lee, Y.L. Ha, and K.C. Chang. 2009. Daidzein administration in vivo reduces myocardial injury in a rat ischemia/reperfusion model by inhibiting NF-κB activation. Life Sciences 84: 227–234.

    Article  PubMed  CAS  Google Scholar 

  31. Yeh, C.H., T.P. Chen, Y.C. Wu, and Y.M. Lin. 2005. Inhibition of NF-κB activation with curcumin attenuates plasma inflammatory cytokines surge and cardiomyocytic apoptosis following cardiac ischemia/reperfusion. The Journal of Surgical Research 125: 109–116.

    Article  PubMed  CAS  Google Scholar 

  32. Nichols, T.C. 2004. NF-κB and reperfusion injury. Drug News & Perspectives 17: 99.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Natural Science Foundation of China (ADW, no. 81173514), National Natural Science Foundation of China (MMX, no. 81001673), the “13115” Technology Innovation Project of Shaanxi Province (MMX, no. 2010ZDKG-62), Natural Science Foundation of Shaanxi Province (MMX, no. 2010JQ4018), Xijing Research Boosting Program (MMX, no. XJZT10D02), and Excellent Civil Service Training Fund of Forth Military Medical University (YG, no. 4138C4IDK6).

Conflicts of Interest

The authors have no conflicting financial interests.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, China

    Guo Wei, Yue Guan, Ying Yin, Jialin Duan, Dan Zhou, Yanrong Zhu, Wei Quan, Miaomiao Xi & Aidong Wen

Authors
  1. Guo Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yue Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jialin Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yanrong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei Quan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Miaomiao Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Aidong Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Miaomiao Xi or Aidong Wen.

Additional information

Guo Wei, Yue Guan, Ying Yin, and Jialin Duan contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wei, G., Guan, Y., Yin, Y. et al. Anti-inflammatory Effect of Protocatechuic Aldehyde on Myocardial Ischemia/Reperfusion Injury In Vivo and In Vitro . Inflammation 36, 592–602 (2013). https://doi.org/10.1007/s10753-012-9581-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-012-9581-z

KEY WORDS

Search

Navigation