Anti-Neuroinflammatory Effects of Vanillin Through the Regulation of Inflammatory Factors and NF-κB Signaling in LPS-Stimulated Microglia
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.
KeywordsMicroglia Vanillin Anti-neuroinflammation
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.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle Scholar