Inflammation

, Volume 41, Issue 2, pp 464–473 | Cite as

Umbelliferone Alleviates Myocardial Ischemia: the Role of Inflammation and Apoptosis

ORIGINAL ARTICLE
First Online:
  • 80 Downloads

Abstract

The present study was to investigate cardioprotective effects of umbelliferone (Umb) on coronary artery ligation-induced myocardial ischemia. The model of myocardial ischemia (MI) was induced by ligatured the left anterior descending coronary artery of SD rats. ST-segment elevation, lactate dehydrogenase (LDH), creatine kinase (CK), catalase (SOD), malondialdehyde (MDA), inflammatory cytokines, Toll-like receptors (TLRs)/nuclear factor (NF)-κBp65 pathway, and apoptosis were evaluated in rats treated with or without Umb. The results showed that Umb treatment could significantly decrease the elevation of the ST segment of electrocardiograph (ECG), the myocardial infarct size of MI significantly. The levels of LDH, CK, and MDA were suppressed, and the content of SOD was enhanced with Umb. The elevated concentration of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 in MI rats was effectively reversed by the Umb administration. Also, TLR/NF-κB and apoptosis-related proteins in MI rats were restored respectively by Umb treatment. The protective effect of Umb against MI injury might be associated with inflammation and apoptosis pathway.

KEY WORDS

umbelliferone myocardial ischemia inflammation apoptosis 
This is a preview of subscription content, log in to check access

Notes

Compliance with Ethical Standards

All animal procedures were performed in strict accordance to the Institutional Animal Research Committee guidelines and approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine.

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Hausenloy, D.J., and D.M. Yellon. 2013. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. The Journal of Clinical Investigation 123: 92–100.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Wang, Y., Z.Z. Zhang, Y. Wu, J. Zhan, X.H. He, and Y.L. Wang. 2013. Honokiol protects rat hearts against myocardial ischemia reperfusion injury by reducing oxidative stress and inflammation. Experimental and Therapeutic Medicine 5: 315–319.CrossRefPubMedGoogle Scholar
  3. 3.
    Chen, O., Z. Ye, Z. Cao, A. Manaenko, K. Ning, X. Zhai, et al. 2016. Methane attenuates myocardial ischemia injury in rats through anti-oxidative, anti-apoptotic and anti-inflammatory actions. Free Radical Biology and Medicine 90: 1–11.CrossRefPubMedGoogle Scholar
  4. 4.
    Suchal, K., Malik, S., Gamad, N., Malhotra, R.K., Goyal, S.N., Chaudhary, U., et al. 2016. Kaempferol attenuates myocardial ischemic injury via inhibition of MAPK signaling pathway in experimental model of myocardial ischemia-reperfusion injury. Oxidative Medicine and Cellular Longevity 2016: 7580731.Google Scholar
  5. 5.
    Dong, L.Y., S. Li, Y.L. Zhen, Y.N. Wang, X. Shao, and Z.G. Luo. 2013. Cardioprotection of vitexin on myocardial ischemia/reperfusion injury in rat via regulating inflammatory cytokines and MAPK pathway. The American Journal of Chinese Medicine 41: 1251–1266.CrossRefPubMedGoogle Scholar
  6. 6.
    Christia, P., and N.G. Frangogiannis. 2013. Targeting inflammatory pathways in myocardial infarction. European Journal of Clinical Investigation 43: 986–995.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Kompa, A.R., and R.J. Summers. 2000. Lidocaine and surgical modification reduces mortality in a rat model of cardiac failure induced by coronary artery ligation. Journal of Pharmacological and Toxicological Methods 43: 199–203.CrossRefPubMedGoogle Scholar
  8. 8.
    Fletcher, P.J., J.M. Pfeffer, M.A. Pfeffer, and E. Braunwald. 1981. Left ventricular diastolic pressure-volume relations in rats with healed myocardial infarction. Effects on systolic function. Circulation Research 49: 618–626.CrossRefPubMedGoogle Scholar
  9. 9.
    Wu, F.J., and S.J. Sheu. 1992. Analysis and processing of Chinese herbal drugs: the study of Fructus Aurantii Immaturus (Chin.). Chinese Pharmaceutical Journal 44: 257–263.CrossRefGoogle Scholar
  10. 10.
    Hoult, J.R.S., and M. Paya. 1996. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. General Pharmacology: The Vascular System 27: 713–722.CrossRefPubMedGoogle Scholar
  11. 11.
    Vasconcelos, J.F., M.M. Teixeira, J.M. Barbosa-Filho, et al. 2009. Effects of umbelliferone in a murine model of allergic airway inflammation[J]. European Journal of Pharmacology 609: 126–131.CrossRefPubMedGoogle Scholar
  12. 12.
    Ramesh, B., and K.V. Pugalendi. 2006. Antioxidant role of umbelliferone in STZ-diabetic rats. Life Sciences 79: 306–310.CrossRefPubMedGoogle Scholar
  13. 13.
    Kofinas, C., I. Chinou, A. Loukis, C. Karvala, C. Roussakis, M. Maillard, et al. 1998. Cytotoxic coumarins from the aqueous parts of Terdyliim apulum and their effects on non-small cell bronchial carcinoma cell lines. Planta Medica 64: 174–176.CrossRefGoogle Scholar
  14. 14.
    Pfeffer, M.A., J.M. Pfeffer, M.C. Fishbein, P.J. Fletcher, J. Spadaro, R.A. Kloner, et al. 1979. Myocardial infarct size and ventricular function in rats. Circulation Research 44: 503–512.CrossRefPubMedGoogle Scholar
  15. 15.
    Killip, T. 1985. Epidemiology of congestive heart failure. The American Journal of Cardiology 56: 2a–6a.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhu, L., T. Wei, X. Chang, H. He, J. Gao, Z. Wen, et al. 2015. Effects of salidroside on myocardial injury in vivo in vitro via regulation of Nox/NF-κB/AP1 pathway. Inflammation 38: 1589–1598.CrossRefPubMedGoogle Scholar
  17. 17.
    Yu, D., M. Li, Y. Tian, J. Liu, and J. Shang. 2015. Luteolin inhibits ROS-activated MAPK pathway in myocardial ischemia/reperfusion injury. Life Sciences 122: 15–25.CrossRefPubMedGoogle Scholar
  18. 18.
    Yang, M., J. Chen, J. Zhao, and M. Meng. 2014. Etanercept attenuates myocardial ischemia/reperfusion injury by decreasing inflammation and oxidative stress. PLoS One 9: e108024.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Hu, X., K. Zhang, C. Xu, Z. Chen, and H. Jiang. 2014. Anti-inflammatory effect of sodium butyrate preconditioning during myocardial ischemia/reperfusion. Experimental and Therapeutic Medicine 8: 229–232.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Zheng, W., L.Z. Huang, L. Zhao, B. Wang, H.B. Xu, G.Y. Wang, et al. 2008. Superoxide dismutase activity and malondialdehyde level in plasma and morphological evaluation of acute severe hemorrhagic shock in rats. The American Journal of Emergency Medicine 26: 54–58.CrossRefPubMedGoogle Scholar
  21. 21.
    Loh, K.P., H.S. Hong, R. De Silva, H. Tan, K. Benny, and Y.Z. Zhun. 2006. Oxidative stress: apoptosis in neuronal injury. Current Alzheimer Research 3: 327–337.CrossRefPubMedGoogle Scholar
  22. 22.
    Niizuma, K., H. Yoshioka, H. Chen, G.S. Kim, J.E. Jung, M. Katsu, et al. 2010. Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1802: 92–99.CrossRefGoogle Scholar
  23. 23.
    Willerson, J.T., and P.M. Ridker. 2004. Inflammation as a cardiovascular risk factor. Circulation 109: II-2–II-10.CrossRefGoogle Scholar
  24. 24.
    Xiao-Peng, C., L. Wei, X. Xue-Feng, L.L. Zhang, and L. Chang-Xiao. 2013. Phytochemical and pharmacological studies on Radix Angelica sinensis. Chinese Journal of Natural Medicines 11: 577–587.CrossRefGoogle Scholar
  25. 25.
    Abe, Y., S. Matsumoto, K. Kito, and N. Ueda. 2000. Cloning and expression of a novel MAPKK-like protein kinase, lymphokine-activated killer T-cell-originated protein kinase, specifically expressed in the testis and activated lymphoid cells. Journal of Biological Chemistry 275: 21525–21531.CrossRefPubMedGoogle Scholar
  26. 26.
    Kyriakis, J.M., and J. Avruch. 1996. Sounding the alarm: protein kinase cascades activated by stress and inflammation. Journal of Biological Chemistry 271: 24313–24316.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Cardiology, Nanjing First HospitalNanjing Medical UniversityNanjingChina

Personalised recommendations