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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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Abstract

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.

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Acknowledgments

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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    1. Department of Pharmacology, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan

      Yuh-Fung Chen

    2. Department of Pharmacy, China Medical University Hospital, Taichung, 40447, Taiwan

      Yuh-Fung Chen & Huei-Yann Tsai

    3. Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 40402, Taiwan

      Yu-Wen Wang

    4. Department of Neurology, China Medical University, Taichung, 40402, Taiwan

      Wei-Shih Huang

    5. Department of Neurology, China Medical University Hospital, Taichung, 40447, Taiwan

      Wei-Shih Huang

    6. Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan

      Ming-Ming Lee

    7. Department of Pharmacology, Geriatric Research, Education and Clinical Center VA Medical Center, University of Minnesota, Minneapolis, MN, 55455, USA

      W. Gibson Wood

    8. Department of Physiology, China Medical University, Taichung, 40402, Taiwan

      Yuk-Man Leung

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    Chen, YF., Wang, YW., Huang, WS. et al. 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. Neuromol Med 18, 322–333 (2016). https://doi.org/10.1007/s12017-016-8395-9

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