Advertisement

Inflammation

, Volume 40, Issue 6, pp 1903–1911 | Cite as

Schisandrin B Ameliorates Myocardial Ischemia/Reperfusion Injury Through Attenuation of Endoplasmic Reticulum Stress-Induced Apoptosis

  • Wei Zhang
  • Zhiqing Sun
  • Fanhua Meng
ORIGINAL ARTICLE

Abstract

Schisandrin B (Sch B), an active composition isolated from the fruit of Schisandra chinensis, has been proved to possess antiinflammatory, antioxidant and anti-endoplasmic reticulum (ER) stress effects in many rodent tissues. However, the exact mechanism of cardioprotective effect of Sch B still needs more study. Here, we detected the effects of Sch B on myocardial ischemia/reperfusion (I/R) injury rats. I/R injury model in this study was established by left anterior descending coronary artery ligation for 40 min followed by 1 h of reperfusion. Male healthy rats were randomly divided into five groups: the sham, I/R, Sch B (20 mg/kg) + I/R, and Sch B (40 mg/kg) + I/R, Sch B (80 mg/kg) + I/R, with 10 rats in each group. We showed that Sch B treatment significantly protected against myocardial I/R injury, as demonstrated by the decrease in the percentage of infarct formation assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining in representative heart tissue slices, comparing with the I/R control group. The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), and total superoxide dismutase (T-SOD) were tested. The ER stress-related proteins such as C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6), and (PKR)-like ER kinase (PERK) were further measured by western blot, and their messenger RNA levels were measured by real-time PCR. The apoptosis of heart tissue cells was also tested through the expressions of caspase-9, caspase-3, Bcl-2, and Bax proteins. Collectively, these results revealed that Sch B exerts protection role on myocardial I/R injury through decreasing oxidative reaction, suppressing ATF6 and PERK pathway, and attenuating ER stress-induced apoptosis.

KEY WORDS

schisandrin B ischemia/reperfusion injury endoplasmic reticulum stress apoptosis 

Notes

Acknowledgements

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Forouzanfar, M.H., A.E. Moran, A.D. Flaxman, G. Roth, G.A. Mensah, M. Ezzati, M. Naghavi, and C.J. Murray. 2012. Assessing the global burden of ischemic heart disease, part 2: analytic methods and estimates of the global epidemiology of ischemic heart disease in 2010. Global Heart 7: 331–342.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ibanez, B., G. Heusch, M. Ovize, and F. Van, de Werf. 2015. Evolving therapies for myocardial ischemia/reperfusion injury. Journal of the American College of Cardiology 65: 1454–1471.CrossRefPubMedGoogle Scholar
  3. 3.
    Chi, H.J., Chen, M.L., Yang, X.C., Lin, X.M., Sun, H., Zhao, W.S., Qi, D., Cai, J., and Dong, J.L. 2016. Progress in therapies for myocardial ischemia reperfusion injury. Current drug targets 17.Google Scholar
  4. 4.
    Yang, Q., G.W. He, M.J. Underwood, and C.M. Yu. 2016. Cellular and molecular mechanisms of endothelial ischemia/reperfusion injury: perspectives and implications for postischemic myocardial protection. American Journal of Translational Research 8: 765–777.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Kalogeris, T., C.P. Baines, M. Krenz, and R.J. Korthuis. 2016. Ischemia/reperfusion. Comprehensive Physiology 7: 113–170.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Moens, A.L., M.J. Claeys, J.P. Timmermans, and C.J. Vrints. 2005. Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process. International Journal of Cardiology 100: 179–190.CrossRefPubMedGoogle Scholar
  7. 7.
    Lu, S.F., Y. Huang, N. Wang, W.X. Shen, S.P. Fu, Q. Li, M.L. Yu, W.X. Liu, X. Chen, X.Y. Jing, and B.M. Zhu. 2016. Cardioprotective effect of electroacupuncture pretreatment on myocardial ischemia/reperfusion injury via antiapoptotic signaling. Evidence-based complementary and alternative medicine : eCAM 2016: 4609784.Google Scholar
  8. 8.
    Xu, C., B. Bailly-Maitre, and J.C. Reed. 2005. Endoplasmic reticulum stress: cell life and death decisions. The Journal of Clinical Investigation 115: 2656–2664.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Liu, M.Q., Z. Chen, and L.X. Chen. 2016. Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases. Acta Pharmacologica Sinica 37: 425–443.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ron, D., and P. Walter. 2007. Signal integration in the endoplasmic reticulum unfolded protein response. Nature Reviews Molecular Cell Biology 8: 519–529.CrossRefPubMedGoogle Scholar
  11. 11.
    Thuerauf, D.J., M. Marcinko, N. Gude, M. Rubio, M.A. Sussman, and C.C. Glembotski. 2006. Activation of the unfolded protein response in infarcted mouse heart and hypoxic cultured cardiac myocytes. Circulation Research 99: 275–282.CrossRefPubMedGoogle Scholar
  12. 12.
    Walter, P., and D. Ron. 2011. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334: 1081–1086.CrossRefPubMedGoogle Scholar
  13. 13.
    Tabas, I., and D. Ron. 2011. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nature Cell Biology 13: 184–190.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Shen, X., K. Zhang, and R.J. Kaufman. 2004. The unfolded protein response—a stress signaling pathway of the endoplasmic reticulum. Journal of Chemical Neuroanatomy 28: 79–92.CrossRefPubMedGoogle Scholar
  15. 15.
    Panossian, A., and G. Wikman. 2008. Pharmacology of Schisandra Chinensis bail.: an overview of Russian research and uses in medicine. Journal of Ethnopharmacology 118: 183–212.CrossRefPubMedGoogle Scholar
  16. 16.
    Ip, S.P., M.K.T. Poon, S.S. Wu, C.T. Che, K.H. Ng, Y.C. Kong, and K.M. Ko. 1995. Effect of Schisandrin-B on hepatic glutathione antioxidant system in mice—protection against carbon-tetrachloride toxicity. Planta Medica 61: 398–401.CrossRefPubMedGoogle Scholar
  17. 17.
    Checker, R., R.S. Patwardhan, D. Sharma, J. Menon, M. Thoh, H.N. Bhilwade, T. Konishi, and S.K. Sandur. 2012. Schisandrin B exhibits anti-inflammatory activity through modulation of the redox-sensitive transcription factors Nrf2 and NF-kappaB. Free Radical Biology & Medicine 53: 1421–1430.CrossRefGoogle Scholar
  18. 18.
    Xu, Y., Liu, Z., Sun, J., Pan, Q.R., Sun, F.F., Yan, Z.Y., and Hu, X. 2011. Schisandrin B prevents doxorubicin-induced chronic cardiotoxicity and enhances its anticancer activity in vivo. Plos One 6.Google Scholar
  19. 19.
    Ko, K.M. 2004. Schisandrin B and other dibenzocyclooctadiene lignans. In: Herbal Medicines: Molecular Basis in Health & Diseases Management. Marcel Dekker New York Basel Hong Kong. 289–314.Google Scholar
  20. 20.
    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
  21. 21.
    Duehrkop, C., and R. Rieben. 2014. Ischemia/reperfusion injury: effect of simultaneous inhibition of plasma cascade systems versus specific complement inhibition. Biochemical Pharmacology 88: 12–22.CrossRefPubMedGoogle Scholar
  22. 22.
    Yim, T.K., and K.M. Ko. 1999. Schisandrin B protects against myocardial ischemia-reperfusion injury by enhancing myocardial glutathione antioxidant status. Molecular and Cellular Biochemistry 196: 151–156.CrossRefPubMedGoogle Scholar
  23. 23.
    Chiu, P.Y., and K.M. Ko. 2003. Time-dependent enhancement in mitochondrial glutathione status and ATP generation capacity by schisandrin B treatment decreases the susceptibility of rat hearts to ischemia-reperfusion injury. BioFactors 19: 43–51.CrossRefPubMedGoogle Scholar
  24. 24.
    Ko, K.M., and H.Y. Yiu. 2001. Schisandrin B modulates the ischemia-reperfusion induced changes in non-enzymatic antioxidant levels in isolated-perfused rat hearts. Molecular and Cellular Biochemistry 220: 141–147.CrossRefPubMedGoogle Scholar
  25. 25.
    Chiu, P.Y., H.Y. Leung, A.H. Siu, M.K. Poon, and K.M. Ko. 2007. Schisandrin B decreases the sensitivity of mitochondria to calcium ion-induced permeability transition and protects against ischemia-reperfusion injury in rat hearts. Acta Pharmacologica Sinica 28: 1559–1565.CrossRefPubMedGoogle Scholar
  26. 26.
    Chiu, P.Y., and K.M. Ko. 2004. Schisandrin B protects myocardial ischemia-reperfusion injury partly by inducing Hsp25 and Hsp70 expression in rats. Molecular and Cellular Biochemistry 266: 139–144.CrossRefPubMedGoogle Scholar
  27. 27.
    Qi, X., A. Vallentin, E. Churchill, and D. Mochly-Rosen. 2007. deltaPKC participates in the endoplasmic reticulum stress-induced response in cultured cardiac myocytes and ischemic heart. Journal of Molecular and Cellular Cardiology 43: 420–428.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Jian, L., Y. Lu, S. Lu, and C. Lu. 2016. Chemical chaperone 4-Phenylbutyric acid reduces cardiac ischemia/reperfusion injury by alleviating endoplasmic reticulum stress and oxidative stress. Medical Science Monitor 22: 5218–5227.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Chen, C.M., C.T. Wu, C.K. Chiang, B.W. Liao, and S.H. Liu. 2012. C/EBP homologous protein (CHOP) deficiency aggravates hippocampal cell apoptosis and impairs memory performance. PloS One 7: e40801.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of ElectrocardiogramLinyi People’s HospitalLinyiPeople’s Republic of China
  2. 2.Department of NeurologyLinyi People’s HospitalLinyiPeople’s Republic of China
  3. 3.Department of Nerve Electrophysiology RoomLinyi People’s HospitalLinyiPeople’s Republic of China

Personalised recommendations