Skip to main content
Erschienen in: Inflammation 4/2016

21.06.2016 | ORIGINAL ARTICLE

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

verfasst von: Zhenlan Li, Cong Hua, Xiaoqiang Pan, Xijia Fu, Wei Wu

Erschienen in: Inflammation | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Dirnagl, U., C. Iadecola, and M.A. Moskowitz. 1999. Pathobiology of ischaemic stroke: an integrated view. Trends in Neurosciences 22: 391–397.CrossRefPubMed Dirnagl, U., C. Iadecola, and M.A. Moskowitz. 1999. Pathobiology of ischaemic stroke: an integrated view. Trends in Neurosciences 22: 391–397.CrossRefPubMed
2.
Zurück zum Zitat 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.CrossRef 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.CrossRef
3.
Zurück zum Zitat Danton, G.H., and W.D. Dietrich. 2003. Inflammatory mechanisms after ischemia and stroke. Journal Neuropathology and Experimental Neurology 62: 127–136.CrossRef Danton, G.H., and W.D. Dietrich. 2003. Inflammatory mechanisms after ischemia and stroke. Journal Neuropathology and Experimental Neurology 62: 127–136.CrossRef
4.
Zurück zum Zitat Lakhan, S.E., A. Kirchgessner, and M. Hofer. 2009. Inflammatory mechanisms in ischemic stroke: therapeutic approaches. Journal of Translational Medicine 7: 97.CrossRefPubMedPubMedCentral Lakhan, S.E., A. Kirchgessner, and M. Hofer. 2009. Inflammatory mechanisms in ischemic stroke: therapeutic approaches. Journal of Translational Medicine 7: 97.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Lindsberg, P.J., and A.J. Grau. 2003. Inflammation and infections as risk factors for ischemic stroke. Stroke 34: 2518–2532.CrossRefPubMed Lindsberg, P.J., and A.J. Grau. 2003. Inflammation and infections as risk factors for ischemic stroke. Stroke 34: 2518–2532.CrossRefPubMed
6.
Zurück zum Zitat 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.PubMedPubMedCentral 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.PubMedPubMedCentral
7.
Zurück zum Zitat 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.PubMedPubMedCentral 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.PubMedPubMedCentral
8.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
9.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
10.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
11.
Zurück zum Zitat 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.CrossRef 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.CrossRef
12.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
13.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat 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.PubMed 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.PubMed
15.
Zurück zum Zitat 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.CrossRef 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.CrossRef
16.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
17.
Zurück zum Zitat 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.CrossRef 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.CrossRef
18.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
19.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
20.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
21.
Zurück zum Zitat 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.CrossRef 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.CrossRef
22.
Zurück zum Zitat 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.CrossRef 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.CrossRef
23.
Zurück zum Zitat 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.PubMed 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.PubMed
24.
Zurück zum Zitat 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.CrossRef 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.CrossRef
25.
Zurück zum Zitat 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.CrossRef 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.CrossRef
26.
Zurück zum Zitat Chan, P.H. 2001. Reactive oxygen radicals in signaling and damage in the ischemic brain. Journal Cerebral Blood Flow and Metabolism 21: 2–14.CrossRef Chan, P.H. 2001. Reactive oxygen radicals in signaling and damage in the ischemic brain. Journal Cerebral Blood Flow and Metabolism 21: 2–14.CrossRef
27.
Zurück zum Zitat 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.CrossRef 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.CrossRef
28.
Zurück zum Zitat Ridder, D., and M. Schwaninger. 2009. NF-kB signaling in cerebral ischemia. Neuroscience 158: 995–1006.CrossRefPubMed Ridder, D., and M. Schwaninger. 2009. NF-kB signaling in cerebral ischemia. Neuroscience 158: 995–1006.CrossRefPubMed
29.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
30.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
31.
Zurück zum Zitat 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.PubMedPubMedCentral 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.PubMedPubMedCentral
32.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
Metadaten
Titel
Carvacrol Exerts Neuroprotective Effects Via Suppression of the Inflammatory Response in Middle Cerebral Artery Occlusion Rats
verfasst von
Zhenlan Li
Cong Hua
Xiaoqiang Pan
Xijia Fu
Wei Wu
Publikationsdatum
21.06.2016
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 4/2016
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-016-0392-5

Weitere Artikel der Ausgabe 4/2016

Inflammation 4/2016 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.