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Anti-Neuroinflammatory Effects of Vanillin Through the Regulation of Inflammatory Factors and NF-κB Signaling in LPS-Stimulated Microglia

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Abstract

Microglia, resident macrophages of the central nervous system (CNS), is responsible for immune responses and homeostasis of the CNS. Microglia plays a complex role in neuroinflammation, which has been implicated in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Therefore, therapeutic agents that suppress the microglia-mediated inflammatory response could potentially be used in the prevention or treatment of neurodegenerative diseases. Vanillin, a primary component of vanilla bean extract, has anti-inflammatory, anticancer, and antitumor properties. However, the effects of vanillin on the anti-neuroinflammatory responses of microglial cells are still poorly understood. In this study, we investigated the mechanism by which vanillin induces anti-neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We found that vanillin significantly decreased the production of nitric oxide and pro-inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Vanillin also reduced the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the mRNA expression levels of IL-1β, TNF-α, and IL-6. Moreover, vanillin inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB. Collectively, these results suggest that vanillin has anti-neuroinflammatory properties and may act as a natural therapeutic agent for neuroinflammatory diseases.

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References

  1. Chen, L., Mo, M., Li, G., Cen, L., Wei, L., Xiao, Y., Chen, X., Li, S., Yang, X., Qu, S., & Xu, P. (2016). The biomarkers of immune dysregulation and inflammation response in Parkinson disease. Translational Neurodegeneration, 5(1), 16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Elsherbiny, N. M., Younis, N. N., Shaheen, M. A., & Elseweidy, M. M. (2016). The synergistic effect between vanillin and doxorubicin in ehrlich ascites carcinoma solid tumor and MCF-7 human breast cancer cell line. Pathology, Research and Practice, 212(9), 767–777.

    Article  CAS  PubMed  Google Scholar 

  3. Takada, L. T. (2017). Innate immunity and inflammation in Alzheimer s disease pathogenesis. Arquivos de Neuro-Psiquiatria, 75(9), 607–608.

    Article  PubMed  Google Scholar 

  4. Dong, Y., Xu, M., Kalueff, A. V., & Song, C. (2017). Dietary eicosapentaenoic acid normalizes hippocampal omega-3 and 6 polyunsaturated fatty acid profile, attenuates glial activation and regulates BDNF function in a rodent model of neuroinflammation induced by central interleukin-1beta administration. European Journal of Nutrition, 57(5), 1781–1791.

    Article  CAS  PubMed  Google Scholar 

  5. Jeitner, T. M., Kalogiannis, M., Krasnikov, B. F., Gomolin, I., Peltier, M. R., & Moran, G. R. (2016). Linking inflammation and Parkinson disease: hypochlorous acid generates parkinsonian poisons. Toxicological Sciences, 153(2), 410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Madeira, M. H., Boia, R., Ambrosio, A. F., & Santiago, A. R. (2017). Having a coffee break: the impact of caffeine consumption on microglia-mediated inflammation in neurodegenerative diseases. Mediators of Inflammation, 2017, 4761081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dulla, Y. A., Kurauchi, Y., Hisatsune, A., Seki, T., Shudo, K., & Katsuki, H. (2016). Regulatory mechanisms of vitamin D3 on production of nitric oxide and pro-inflammatory cytokines in microglial BV-2 cells. Neurochemical Research, 41(11), 2848–2858.

    Article  CAS  PubMed  Google Scholar 

  8. Han, B. H., Lee, Y. J., Yoon, J. J., Choi, E. S., Namgung, S., Jin, X. J., Jeong, D. H., Kang, D. G., & Lee, H. S. (2017). Hwangryunhaedoktang exerts anti-inflammation on LPS-induced NO production by suppressing MAPK and NF- kappaB activation in RAW264.7 macrophages. J Integrative Medicine, 15(4), 326–336.

    Article  Google Scholar 

  9. Kim, D. H., Kim, M. E., & Lee, J. S. (2015). Inhibitory effects of extract from G. lanceolata on LPS-induced production of nitric oxide and IL-1beta via down-regulation of MAPK in macrophages. Applied Biochemistry and Biotechnology, 175(2), 657–665.

    Article  CAS  PubMed  Google Scholar 

  10. Deng, G., He, H., Chen, Z., OuYang, L., Xiao, X., Ge, J., Xiang, B., Jiang, S., & Cheng, S. (2017). Lianqinjiedu decoction attenuates LPS-induced inflammation and acute lung injury in rats via TLR4/NF-kappa B pathway. Biomedicine & Pharmacotherapy, 96, 148–152.

    Article  Google Scholar 

  11. Abhimannue, A. P., Mohan, M. C., & Prakash Kumar B. (2016). Inhibition of tumor necrosis factor-alpha and interleukin-1beta production in lipopolysaccharide-stimulated monocytes by methanolic extract of Elephantopus scaber Linn and Identification of bioactive components. Applied Biochemistry and Biotechnology, 179(3), 427–443.

    Article  CAS  PubMed  Google Scholar 

  12. Srinual, S., Chanvorachote, P., & Pongrakhananon, V. (2017). Suppression of cancer stem-like phenotypes in NCI-H460 lung cancer cells by vanillin through an Akt-dependent pathway. International Journal of Oncology, 50(4), 1341–1351.

    Article  CAS  PubMed  Google Scholar 

  13. Al Asmari, A., Al Shahrani, H., Al Masri, N., Al Faraidi, A., Elfaki, I., & Arshaduddin, M. (2016). Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation. Toxicology Reports, 3, 105–113.

    Article  CAS  PubMed  Google Scholar 

  14. Liu, J., & Mori, A. (1993). Antioxidant and pro-oxidant activities of p-hydroxybenzyl alcohol and vanillin: effects on free radicals, brain peroxidation and degradation of benzoate, deoxyribose, amino acids and DNA. Neuropharmacology, 32(7), 659–669.

    Article  CAS  PubMed  Google Scholar 

  15. Rehman, M. U., Tahir, M., Khan, A. Q., Khan, R., Oday, O. H., Lateef, A., Hassan, S. K., Rashid, S., Ali, N., Zeeshan, M., & Sultana, S. (2014). D-limonene suppresses doxorubicin-induced oxidative stress and inflammation via repression of COX-2, iNOS, and NFkappaB in kidneys of Wistar rats. Experimental Biology and Medicine (Maywood, N.J.), 239(4), 465–476.

    Article  CAS  Google Scholar 

  16. Zhao, D., Kwon, S. H., Chun, Y. S., Gu, M. Y., & Yang, H. O. (2017). Anti-neuroinflammatory effects of fucoxanthin via inhibition of Akt/NF-kappaB and MAPKs/AP-1 pathways and activation of PKA/CREB pathway in lipopolysaccharide-activated BV-2 microglial cells. Neurochemical Research, 42(2), 667–677.

    Article  CAS  PubMed  Google Scholar 

  17. Park, S. Y., Jin, M. L., Kang, N. J., Park, G., & Choi, Y. W. (2017). Anti-inflammatory effects of novel polygonum multiflorum compound via inhibiting NF-kappaB/MAPK and upregulating the Nrf2 pathways in LPS-stimulated microglia. Neuroscience Letters, 651, 43–51.

    Article  CAS  PubMed  Google Scholar 

  18. Phull, A. R., Eo, S. H., & Kim, S. J. (2017). Oleanolic acid (OA) regulates inflammation and cellular dedifferentiation of chondrocytes via MAPK signaling pathways. Cellular and Molecular Biology (Noisy-le-Grand, France), 63(3), 12–17.

    Article  Google Scholar 

  19. Chan, C. K., Tan, L. T., Andy, S. N., Kamarudin, M. N. A., Goh, B. H., & Kadir, H. A. (2017). Anti-neuroinflammatory activity of elephantopus scaber L. via activation of Nrf2/HO-1 signaling and inhibition of p38 MAPK pathway in LPS-induced microglia BV-2 cells. Frontiers in Pharmacology, 8, 397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chang, C., Wang, K., Zhou, S. N., Wang, X. D., & Wu, J. E. (2017). Protective effect of Saccharomyces boulardii on deoxynivalenol-induced injury of porcine macrophage via attenuating p38 MAPK signal pathway. Applied Biochemistry and Biotechnology, 182(1), 411–427.

    Article  CAS  PubMed  Google Scholar 

  21. Cantacorps, L., Alfonso-Loeches, S., Moscoso-Castro, M., Cuitavi, J., Gracia-Rubio, I., Lopez-Arnau, R., Escubedo, E., Guerri, C., & Valverde, O. (2017). Maternal alcohol binge drinking induces persistent neuroinflammation associated with myelin damage and behavioural dysfunctions in offspring mice. Neuropharmacology, 123, 368–384.

    Article  CAS  PubMed  Google Scholar 

  22. Karthikeyan, A., Patnala, R., Jadhav, S. P., Eng-Ang, L., & Dheen, S. T. (2016). MicroRNAs: key players in microglia and astrocyte mediated inflammation in CNS pathologies. Current Medicinal Chemistry, 23(30), 3528–3546.

    Article  CAS  PubMed  Google Scholar 

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Funding

This research was supported by a grant from Marine Biotechnology Program (PJT200669) funded by the Ministry of Oceans and Fisheries and the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2017R1D1A1B03034673), Korea.

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Author notes

  1. Mi Eun Kim and Ju Yong Na contributed equally to this work.

Authors and Affiliations

  1. Department of Life Science, Immunology Research Lab, BK21-plus Research Team for Bioactive Control Technology, College of Natural Sciences, Chosun University, Dong-gu, Gwangju, 501-759, Republic of Korea

    Mi Eun Kim, Ju Yong Na & Jun Sik Lee

  2. Djkunghee Hospital, Department of Preventive and Society Dentistry, School of Dentistry, Kyung Hee University, Seoul, 02447, South Korea

    Yong-Duk Park

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  1. Mi Eun Kim
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  2. Ju Yong Na
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Correspondence to Yong-Duk Park or Jun Sik Lee.

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Kim, M.E., Na, J.Y., Park, YD. et al. Anti-Neuroinflammatory Effects of Vanillin Through the Regulation of Inflammatory Factors and NF-κB Signaling in LPS-Stimulated Microglia. Appl Biochem Biotechnol 187, 884–893 (2019). https://doi.org/10.1007/s12010-018-2857-5

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  • DOI: https://doi.org/10.1007/s12010-018-2857-5

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