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Carvacrol Exerts Neuroprotective Effects Via Suppression of the Inflammatory Response in Middle Cerebral Artery Occlusion Rats

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Abstract

Increasing evidence demonstrates that inflammation plays an important role in cerebral ischemia. Carvacrol, a monoterpenic phenol, is naturally occurring in various plants belonging to the family Lamiaceae and exerts protective effects in a mice model of focal cerebral ischemia/reperfusion injury by reducing infarct volume and decreasing the expression of cleaved caspase-3. However, the anti-inflammatory mechanisms by which carvacrol protect the brain have yet to be fully elucidated. We investigated the effects of carvacrol on inflammatory reaction and inflammatory mediators in middle cerebral artery occlusion rats. The results of the present study showed that carvacrol inhibited the levels of inflammatory cytokines and myeloperoxidase (MPO) activity, as well as the expression of iNOS and COX-2. It also increased SOD activity and decreased MDA level in ischemic cortical tissues. In addition, carvacrol treatment suppressed the ischemia/reperfusion-induced increase in the protein expression of nuclear NF-kB p65. In conclusion, we have shown that carvacrol inhibits the inflammatory response via inhibition of the NF-kB signaling pathway in a rat model of focal cerebral ischemia. Therefore, carvacrol may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

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References

  1. Dirnagl, U., C. Iadecola, and M.A. Moskowitz. 1999. Pathobiology of ischaemic stroke: an integrated view. Trends in Neurosciences 22: 391–397.

    Article  CAS  PubMed  Google Scholar 

  2. Woitzik, J., T. Back, and C. Thome. 2007. Flow-dependent versus spreading-like impairment of brain tissue integrity during focal cerebral ischemia and its consequences for neuroprotective strategies. Frontiers in Bioscience 13: 1500–1506.

    Article  Google Scholar 

  3. Danton, G.H., and W.D. Dietrich. 2003. Inflammatory mechanisms after ischemia and stroke. Journal Neuropathology and Experimental Neurology 62: 127–136.

    Article  CAS  Google Scholar 

  4. Lakhan, S.E., A. Kirchgessner, and M. Hofer. 2009. Inflammatory mechanisms in ischemic stroke: therapeutic approaches. Journal of Translational Medicine 7: 97.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lindsberg, P.J., and A.J. Grau. 2003. Inflammation and infections as risk factors for ischemic stroke. Stroke 34: 2518–2532.

    Article  PubMed  Google Scholar 

  6. Ultee, A., E. Kets, and E. Smid. 1999. Mechanisms of action of carvacrol on the food-borne pathogen Bacillus cereus. Applied Environmental Microbiology 65: 4606–4610.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Türkcü, G., U. Alabalık, A.N. Keleş, M. Bozkurt, İ. İbiloğlu, U. Fırat, and H. Büyükbayram. 2015. Protective effects of carvacrol and pomegranate against methotrexate-induced intestinal damage in rats. International Journal of Clinical Experimental Medicine 8: 15474–15481.

    PubMed  PubMed Central  Google Scholar 

  8. Lee, K.P., G.W. Sudjarwo, S.H. Jung, D. Lee, D.-Y. Lee, G.B. Lee, S. Baek, D.-Y. Kim, H.M. Lee, and B. Kim. 2015. Carvacrol inhibits atherosclerotic neointima formation by downregulating reactive oxygen species production in vascular smooth muscle cells. Atherosclerosis 240: 367–373.

    Article  CAS  PubMed  Google Scholar 

  9. Yin, Q.-h., F.-X. Yan, X.-Y. Zu, Y.-H. Wu, X.-P. Wu, M.-C. Liao, S.-W. Deng, L.-l. Yin, and Y.-Z. Zhuang. 2012. Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2. Cytotechnology 64: 43–51.

    Article  CAS  PubMed  Google Scholar 

  10. Aristatile, B., A.H. Al-Assaf, and K.V. Pugalendi. 2013. Carvacrol suppresses the expression of inflammatory marker genes in D-galactosamine-hepatotoxic rats. Asian Pacific Journal of Tropical Medicine 6: 205–211.

    Article  CAS  PubMed  Google Scholar 

  11. da Silva Lima, M., L.J. Quintans-Júnior, W.A. de Santana, C.M. Kaneto, M.B.P. Soares, and C.F. Villarreal. 2013. Anti-inflammatory effects of carvacrol: evidence for a key role of interleukin-10. European Journal of Pharmacology 699: 112–117.

    Article  Google Scholar 

  12. Guimarães, A.G., M.A. Xavier, M.T. de Santana, E.A. Camargo, C.A. Santos, F.A. Brito, E.O. Barreto, S.C. Cavalcanti, Â.R. Antoniolli, and R.C. Oliveira. 2012. Carvacrol attenuates mechanical hypernociception and inflammatory response. Naunyn-Schmiedeberg’s Archives of Pharmacology 385: 253–263.

    Article  PubMed  Google Scholar 

  13. Yu, H., Z.-L. Zhang, J. Chen, A. Pei, F. Hua, X. Qian, J. He, C.-F. Liu, and X. Xu. 2012. Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice. PLoS ONE 7, e33584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Clark, W.M., N.S. Lessov, M.P. Dixon, and F. Eckenstein. 1997. Monofilament intraluminal middle cerebral artery occlusion in the mouse. Neurological Research 19: 641–648.

    CAS  PubMed  Google Scholar 

  15. Perera, M.N., H.K. Ma, S. Arakawa, D.W. Howells, R. Markus, C.C. Rowe, and G.A. Donnan. 2006. Inflammation following stroke. Journal of Clinical Neuroscience 13: 1–8.

    Article  CAS  Google Scholar 

  16. Zoppo, G., I. Ginis, J.M. Hallenbeck, C. Iadecola, X. Wang, and G.Z. Feuerstein. 2000. Inflammation and stroke: putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia. Brain Pathology 10: 95–112.

    Article  PubMed  Google Scholar 

  17. Arvin, B., L.F. Neville, F.C. Barone, and G.Z. Feuerstein. 1996. The role of inflammation and cytokines in brain injury. Neuroscience & Biobehavioral Reviews 20: 445–452.

    Article  CAS  Google Scholar 

  18. Saito, K., K. Suyama, K. Nishida, Y. Sei, and A.S. Basile. 1996. Early increases in TNF-α, IL-6 and IL-1β levels following transient cerebral ischemia in gerbil brain. Neuroscience Letters 206: 149–152.

    Article  CAS  PubMed  Google Scholar 

  19. Yenari, M.A., J. Liu, Z. Zheng, Z.S. Vexler, J.E. Lee, and R.G. Giffard. 2005. Antiapoptotic and anti‐inflammatory mechanisms of heat‐shock protein protection. Annals of the New York Academy of Sciences 1053: 74–83.

    Article  CAS  PubMed  Google Scholar 

  20. Matsuo, Y., H. Onodera, Y. Shiga, M. Nakamura, M. Ninomiya, T. Kihara, and K. Kogure. 1994. Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke 25: 1469–1475.

    Article  CAS  PubMed  Google Scholar 

  21. Salvemini, D., T.P. Misko, J.L. Masferrer, K. Seibert, M.G. Currie, and P. Needleman. 1993. Nitric oxide activates cyclooxygenase enzymes. Proceedings of the National Academy of Sciences of United States of America 90: 7240–7244.

    Article  CAS  Google Scholar 

  22. Iadecola, C., F. Zhang, S. Xu, R. Casey, and M.E. Ross. 1995. Inducible nitric oxide synthase gene expression in brain following cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism 15: 378–378.

    Article  CAS  Google Scholar 

  23. Nogawa, S., F. Zhang, M.E. Ross, and C. Iadecola. 1997. Cyclo-oxygenase-2 gene expression in neurons contributes to ischemic brain damage. Journal of Neuroscience 17: 2746–2755.

    CAS  PubMed  Google Scholar 

  24. Nakayama, M., K. Uchimura, R.L. Zhu, T. Nagayama, M.E. Rose, R.A. Stetler, P.C. Isakson, J. Chen, and S.H. Graham. 1998. Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia. Proceedings of the National Academy of Sciences of United States of America 95: 10954–10959.

    Article  CAS  Google Scholar 

  25. Adibhatla, R.M., and J. Hatcher. 2006. Phospholipase A 2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Radical Biology & Medicine 40: 376–387.

    Article  Google Scholar 

  26. Chan, P.H. 2001. Reactive oxygen radicals in signaling and damage in the ischemic brain. Journal Cerebral Blood Flow and Metabolism 21: 2–14.

    Article  CAS  Google Scholar 

  27. Harari, O.A., and J.K. Liao. 2010. NF‐kB and innate immunity in ischemic stroke. Annals of New York Academy of Sciences 1207: 32–40.

    Article  CAS  Google Scholar 

  28. Ridder, D., and M. Schwaninger. 2009. NF-kB signaling in cerebral ischemia. Neuroscience 158: 995–1006.

    Article  CAS  PubMed  Google Scholar 

  29. Hu, X., O. Nesic‐Taylor, J. Qiu, H.C. Rea, R. Fabian, D.K. Rassin, and J.R. Perez‐Polo. 2005. Activation of nuclear factor‐kB signaling pathway by interleukin‐1 after hypoxia/ischemia in neonatal rat hippocampus and cortex. Journal of Neurochemistry 93: 26–37.

    Article  CAS  PubMed  Google Scholar 

  30. Xu, M., L. Yang, L.-Z. Hong, X.-Y. Zhao, and H.-L. Zhang. 2012. Direct protection of neurons and astrocytes by matrine via inhibition of the NF-kB signaling pathway contributes to neuroprotection against focal cerebral ischemia. Brain Research 1454: 48–64.

    Article  CAS  PubMed  Google Scholar 

  31. Sun, B.-Z., L. Chen, Q. Wu, H.-L. Wang, X.-B. Wei, Y.-X. Xiang, and X.-M. Zhang. 2014. Suppression of inflammatory response by flurbiprofen following focal cerebral ischemia involves the NF-kB signaling pathway. International Journal of Clinical and Experimental Medicine 7: 3087–3095.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Herrmann, O., B. Baumann, R. de Lorenzi, S. Muhammad, W. Zhang, J. Kleesiek, M. Malfertheiner, M. Köhrmann, I. Potrovita, and I. Maegele. 2005. IKK mediates ischemia-induced neuronal death. Nature Medicine 11: 1322–1329.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Rehabilitation, The First Hospital of Jilin University, Xinmin Street No.71, Changchun, 130021, Jilin, China

    Zhenlan Li

  2. Department of Neurosurgery, The First Hospital of Jilin University, Xinmin Street No.71, Changchun, 130021, Jilin, China

    Cong Hua, Xiaoqiang Pan & Wei Wu

  3. Department of Neurology, The First Hospital of Jilin University, Xinmin Street No.71, Changchun, 130021, Jilin, China

    Xijia Fu

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  1. Zhenlan Li
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  2. Cong Hua
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  5. Wei Wu
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Correspondence to Wei Wu.

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Li, Z., Hua, C., Pan, X. et al. Carvacrol Exerts Neuroprotective Effects Via Suppression of the Inflammatory Response in Middle Cerebral Artery Occlusion Rats. Inflammation 39, 1566–1572 (2016). https://doi.org/10.1007/s10753-016-0392-5

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  • DOI: https://doi.org/10.1007/s10753-016-0392-5

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