Trans-Cinnamaldehyde, An Essential Oil in Cinnamon Powder, Ameliorates Cerebral Ischemia-Induced Brain Injury via Inhibition of Neuroinflammation Through Attenuation of iNOS, COX-2 Expression and NFκ-B Signaling Pathway
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Trans-cinnamaldehyde (TCA), an essential oil in cinnamon powder, may have beneficial effects as a treatment for stroke which is the second leading cause of death worldwide. Post-ischemic inflammation induces neuronal cell damage after stroke, and activation of microglia, in particular, has been thought as the main contributor of proinflammatory and neurotoxic factors. The purpose of this study was to investigate the neuroprotective effects of TCA in an animal model of ischemia/reperfusion (I/R)-induced brain injury and the neuroprotective mechanism was verified in LPS-induced inflammation of BV-2 microglial cells. Our results showed that TCA (10–30 mg/kg, p.o.) significantly reduced the infarction area, neurological deficit score and decreased iNOS and COX-2 protein expression level in I/R-induced injury brain tissue. It inhibited 0.5 µg/ml LPS-induced NO production in BV-2 microglial cells without affecting cell viability, reduced protein expression of iNOS and COX-2, and attenuated inhibition of p53 protein. TCA also suppressed the effects of LPS-induced nuclear translocation of NF-κB p65 and p50 and increased cytosolic IκBα. It also reduced LPS-induced mRNA expression of iNOS, COX-2, and TNFα. We concluded that TCA has a potential neuroprotective effect to against the ischemic stroke, which may be via the inhibition of neuroinflammation through attenuating iNOS, COX-2 expression and NF-κB signaling pathway.
KeywordsTrans-cinnamaldehyde Cerebral ischemia BV-2 microglia Neuroinflammation NF-κB signaling pathway
Authors would like to thank Dr Igbavboa (Department of Pharmacology, University of Minnesota School of Medicine) for guiding the QRT-PCR technique. This work was supported by Grants from the Ministry of Science and Technology (NSC95-2320-B-039-037), China Medical University (CMU-101-ASIA-06 and CMU102-ASIA-14) and the National Institutes of Health, AG-23524 and AG-18357.
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Conflict of interest
Authors have no conflict of interest to declare.
- Bernardo, M. A., Silva, M. L., Santos, E., Moncada, M. M., Brito, J., Proenca, L., et al. (2015). Effect of cinnamon tea on postprandial glucose concentration. Journal of Diabetes Research. Article ID 913651.Google Scholar
- Bhat, N. R., Zhang, P., Lee, J. C., & Hogan, E. L. (1998). Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric oxide synthase and tumor necrosis factor-alpha gene expression endotoxin- stimulated primary glial cultures. Journal of Neuroscience, 18, 1633–1641.PubMedGoogle Scholar
- Gill, R., Sibson, N. R., Hatfield, R. H., Burdett, N. G., Carpenter, T. A., Hall, L. D., et al. (1995). A comparison of the early development of ischemic damage following permanent middle cerebral artery occlusion in rats as assessed using magnetic resonance imaging and histology. Journal of Cerebrocascular Blood Flow and Metabolism, 15, 1–11.CrossRefGoogle Scholar
- Hoozemans, J. J., Veerhuis, R., Janssen, I., van Elk, E. J., Rozemuller, A. J., & Eikelenboom, P. (2002). The role of cyclo-oxygenase 1 and 2 activity in prostaglandin E(2) secretion by cultured human adult microglia: Implications for Alzheimer’s disease. Brain Research, 951, 218–226.CrossRefPubMedGoogle Scholar
- Huang, W. W., Ko, S. W., Tsai, H. Y., Chung, J. G., Chiang, J. H., Chen, K. T., et al. (2011). Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways. International Journal of Oncology, 38(4), 1067–1073.PubMedGoogle Scholar
- Jung, W. K., Ahn, Y. W., Lee, S. H., Choi, Y. H., Kim, S. K., Yea, S. S., et al. (2009). Ecklonia cava ethanolic extracts inhibit lioppolysaccaharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV2 microglia via the MAPK kinase and NF-kB pathways. Food and Chemical Toxicology, 47, 410–417.CrossRefPubMedGoogle Scholar
- Lee, Y. J., Lee, S. R., Choi, S. S., Yeo, H. G., Chang, K. T., & Lee, H. J. (2014). Therapeutically targeting neuroinflammation and microglia after acute ischemic stroke. Biomed Research International. Article ID 297241.Google Scholar
- Lee, S. C., Liu, W., Dickson, D. W., Brosnan, C. F., & Berman, J. W. (1993). Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 β. Journal of Immunology, 150, 2659–2667.Google Scholar
- Liao, J. C., Deng, J. S., Chiu, C. S., Hou, W. C., Huang, S. S., Shie, P. H., et al. (2012). Anti-inflammatory activities of cinnamomum cassia constituents in vitro and in vivo. Evidence-Based Complementary and Alternative Medicine. Article ID 429320.Google Scholar
- Umezawa, K., Ariga, A., & Matsumoto, N. (2000). Naturally occurring and synthetic inhibitors of NF-kappa B function. Anticancer Drug Design, 15, 239–244.Google Scholar
- Woo, M. S., Jang, P. G., Park, J. S., Kim, W. K., Joh, T. H., & Kim, H. S. (2003). Selective modulation of lipopolysaccharide-stimulated cytokine expression and mitogen-activated protein kinase pathways by dibutyryl-cAMP in BV2 microglial cells. Brain Research Molecular Brain Research, 113, 86–96.CrossRefPubMedGoogle Scholar
- Wu, K. J., Chen, Y. F., Tsai, H. Y., Wu, C. R., & Wood, W. G. (2012). Guizhi-Fuling-Wan, a traditional Chinese herbal medicine, ameliorates memory deficits and neuronal apoptosis in the streptozotocin-induced hyperglycemic rodents via the decrease of Bax/Bcl2 ratio and caspase-3 expression. Evidence-Based Complementary and Alternative Medicine. Article ID 656150.Google Scholar
- Yang, G., Kitagawa, K., Matsushita, K., Mabuchi, T., Yagita, Y., Yanagihara, T., et al. (1997). C57BL/6 is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: Selective neuronal death in the murine transient forebrain ischemia. Brain Research, 752, 209–218.CrossRefPubMedGoogle Scholar