DOI QR코드

DOI QR Code

Carpomitra costata Extract Alleviates Lipopolysaccharide-induced Neuroinflammatory Responses in BV2 Microglia through the Inactivation of NF-κB Associated with the Blockade of the TLR4 Pathway and ROS Generation

  • Park, Cheol (Division of Basic Sciences, College of Liberal Studies, Dong-eui University) ;
  • Cha, Hee-Jae (Department of Parasitology and Genetics, Kosin University College of Medicine) ;
  • Hong, Su-Hyun (Department of Biochemistry, Dong-eui University College of Korean Medicine) ;
  • Kim, Suhkmann (Department of Chemistry, College of Natural Sciences, Pusan National University) ;
  • Kim, Heui-Soo (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Choi, Yung Hyun (Department of Biochemistry, Dong-eui University College of Korean Medicine)
  • Received : 2020.05.03
  • Accepted : 2020.05.11
  • Published : 2020.06.30

Abstract

In this study, we investigated the inhibitory potential of an ethanol extract of Carpomitra costata (EECC) (Stackhouse) Batters, a brown alga, against neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results showed that EECC significantly suppressed the LPS-induced secretion of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E2, with no significant cytotoxic effects. EECC also inhibited the LPS-induced expression of their regulatory enzymes, such as inducible NO synthase and cyclooxygenase-2. In addition, EECC downregulated the LPS-induced expression and production of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β. In the mechanistic assessment of the antineuroinflammatory effects, EECC was found to inhibit the nuclear translocation and DNA binding of nuclear factor-kappa B (NF-κB) by disrupting the degradation of the κB-α inhibitor in the cytoplasm. Moreover, EECC effectively suppressed the enhanced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88, as well as the binding of LPS to TLR4 in LPS-treated BV2 cells. Furthermore, EECC markedly reduced the LPS-induced generation of reactive oxygen species (ROS), demonstrating a strong antioxidative effect. Collectively, these results suggest that EECC repressed LPS-mediated inflammatory action in the BV2 microglia through the inactivation of NF-κB signaling by antagonizing TLR4 and/or preventing ROS accumulation. While further studies are needed to fully understand the anti-inflammatory effects associated with the antioxidant activity of EECC, the current findings suggest that EECC has a potential advantage in inhibiting the onset and treatment of neuroinflammatory diseases.

Keywords

References

  1. Cherry, J. D., Olschowka, J. A. and O'Banion, M. K. 2014. Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J. Neuroinflammation 11, 98. https://doi.org/10.1186/1742-2094-11-98
  2. Choi, H. I., Choi, J. P., Seo, J., Kim, B. J., Rho, M., Han, J. K. and Kim, J. G. 2017. Helicobacter pylori-derived extracellular vesicles increased in the gastric juices of gastric adenocarcinoma patients and induced inflammation mainly via specific targeting of gastric epithelial cells. Exp. Mol. Med. 49, e330. https://doi.org/10.1038/emm.2017.47
  3. Daulatzai, M. A. 2016. Fundamental role of pan-inflammation and oxidative-nitrosative pathways in neuropathogenesis of Alzheimer's disease in focal cerebral ischemic rats. Am. J. Neurodegener. Dis. 5, 102-130.
  4. de Jesus Raposo, M. F., de Morais, A. M. and de Morais, R. M. 2015. Marine polysaccharides from algae with potential biomedical applications. Mar. Drugs 13, 2967-3028. https://doi.org/10.3390/md13052967
  5. Fan, H., Wu, P. F., Zhang, L., Hu Z. L., Wang, W., Guan, X. L., Luo, H., Ni, M., Yang, J. W., Li, M. X., Chen, J. G. and Wang, F. 2015. Methionine sulfoxide reductase A negatively controls microglia-mediated neuroinflammation via inhibiting ROS/MAPKs/NF-${\kappa}B$ signaling pathways through a catalytic antioxidant function. Antioxid. Redox Signal. 22, 832-847. https://doi.org/10.1089/ars.2014.6022
  6. Fernando, I. P., Kim, M., Son, K. T., Jeong, Y. and Jeon, Y. J. 2016. Antioxidant activity of marine algal polyphenolic compounds: A mechanistic approach. J. Med. Food 19, 615-628. https://doi.org/10.1089/jmf.2016.3706
  7. Fetisova, E., Chernyak, B., Korshunova, G., Muntyan, M. and Skulachev, V. 2017. Mitochondria-targeted antioxidants as a prospective therapeutic strategy for multiple sclerosis. Curr. Med. Chem. 24, 2086-2114.
  8. Garcia, G., Nanni, S., Figueira, I., Ivanov, I., McDougall, G. J., Stewart, D., Ferreira, R. B., Pinto, P., Silva, R. F., Brites, D. and Santos, C. N. 2017. Bioaccessible (poly)phenol metabolites from raspberry protect neural cells from oxidative stress and attenuate microglia activation. Food Chem. 215, 274-283. https://doi.org/10.1016/j.foodchem.2016.07.128
  9. Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C. and Gage, F. H. 2010. Mechanisms underlying inflammation in neurodegeneration. Cell 140, 918-934. https://doi.org/10.1016/j.cell.2010.02.016
  10. Gomez-Nicola, D. and Perry, V. H. 2015. Microglial dynamics and role in the healthy and diseased brain: a paradigm of functional plasticity. Neuroscientist 21, 169-184. https://doi.org/10.1177/1073858414530512
  11. Iizumi, T., Takahashi, S., Mashima, K., Minami, K., Izawa, Y., Abe, T., Hishiki, T., Suematsu, M., Kajimura, M. and Suzuki, N. 2016. A possible role of microglia-derived nitric oxide by lipopolysaccharide in activation of astroglial pentose-phosphate pathway via the Keap1/Nrf2 system. J. Neuroinflammation 13, 99. https://doi.org/10.1186/s12974-016-0564-0
  12. Joh, E. H. and Kim, D. H. 2010. Lancemaside A inhibits lipopolysaccharide-induced inflammation by targeting LPS/TLR4 complex. J. Cell. Biochem. 111, 865-871. https://doi.org/10.1002/jcb.22773
  13. Kang, H. J., Jeong, J. S., Park, N. J., Go, G. B., Kim, S. O., Park, C., Kim, B. W., Hong, S. H. and Choi, Y. H. 2017. An ethanol extract of Aster yomena (Kitam.) Honda inhibits lipopolysaccharide-induced inflammatory responses in murine RAW 264.7 macrophages. Biosci. Trends 11, 85-94. https://doi.org/10.5582/bst.2016.01217
  14. Kim, S. H., Kim, K. J., Kim, J. H., Kwak, J. H., Song, H., Cho, J. Y., Hwang, D. Y., Kim, K. S. and Jung, Y. S. 2017. Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources. Lab. Anim. Res. 33, 165-170. https://doi.org/10.5625/lar.2017.33.2.165
  15. Kim, Y. E., Hwang, C. J., Lee, H. P., Kim, C. S., Son, D. J., Ham, Y. W., Hellstrom, M., Han, S. B., Kim, H. S., Park, E. K. and Hong, J. T. 2017. Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB. Neuropharmacology 117, 21-32. https://doi.org/10.1016/j.neuropharm.2017.01.025
  16. Kopitar-Jerala, N. 2015. Innate immune response in brain, NF-Kappa B signaling and cystatins. Front. Mol. Neurosci. 8, 73. https://doi.org/10.3389/fnmol.2015.00073
  17. Lee, M. B., Lee, J. H., Hong, S. H., You, J. S., Nam, S. T., Kim, H. W., Park, Y. H., Lee, D., Min, K. Y., Park, Y. M., Kim, Y. M., Kim, H. S. and Choi, W. S. 2017. JQ1, a BET inhibitor, controls TLR4-induced IL-10 production in regulatory B cells by BRD4-NF-${\kappa}B$ axis. BMB Rep. 50, 640-646. https://doi.org/10.5483/BMBRep.2017.50.12.194
  18. Li, Q. and Verma, I. M. 2002. NF-kappaB regulation in the immune system. Nat. Rev. Immunol. 2, 725-734. https://doi.org/10.1038/nri910
  19. Ohl, K., Tenbrock, K. and Kipp, M. 2016. Oxidative stress in multiple sclerosis: Central and peripheral mode of action. Exp. Neurol. 277, 58-67. https://doi.org/10.1016/j.expneurol.2015.11.010
  20. Park, Y. S., Kwon, Y. J. and Chun, Y. J. 2017. CYP1B1 Activates Wnt/${\beta}$-catenin signaling through suppression of Herc5-mediated ISGylation for protein degradation on ${\beta}$-catenin in HeLa cells. Toxicol. Res. 33, 211-218. https://doi.org/10.5487/TR.2017.33.3.211
  21. Pesando, D. and Caram, B. 1984. Screening of marine algae from the French mediterranean coast for antibacterial and antifungal activity. Bot. Mar. 27, 381-386.
  22. Qin, L., Liu, Y., Hong, J. S. and Crews, F. T. 2013. NADPH oxidase and aging drive microglial activation, oxidative stress, and dopaminergic neurodegeneration following systemic LPS administration. Glia 61, 855-868. https://doi.org/10.1002/glia.22479
  23. Roohinejad, S., Koubaa, M., Barba, F. J., Saljoughian, S., Amid, M. and Greiner, R. 2017. Application of seaweeds to develop new food products with enhanced shelf-life, quality and health-related beneficial properties. Food Res. Int. 99, 1066-1083. https://doi.org/10.1016/j.foodres.2016.08.016
  24. Slusarczyk, J., Trojan, E., Glombik, K., Piotrowska, A., Budziszewska, B., Kubera, M., Popiolek-Barczyk, K., Lason, W., Mika, J. and Basta-Kaim, A. 2016. Anti-inflammatory properties of tianeptine on lipopolysaccharide-induced changes in microglial cells involve toll-like receptor-related pathways. J. Neurochem. 136, 958-970. https://doi.org/10.1111/jnc.13452
  25. Tremblay, M. E., Stevens, B., Sierra, A., Wake, H., Bessis, A. and Nimmerjahn, A. 2011. The role of microglia in the healthy brain. J. Neurosci. 31, 16064-16069. https://doi.org/10.1523/JNEUROSCI.4158-11.2011
  26. von Leden, R. E., Yauger, Y. J., Khayrullina, G. and Byrnes, K. R. 2017. Central nervous system injury and nicotinamide adenine dinucleotide phosphate oxidase: Oxidative stress and therapeutic targets. J. Neurotrauma. 34, 755-764. https://doi.org/10.1089/neu.2016.4486
  27. Wang, X., Wang, C., Wang, J., Zhao, S., Zhang, K., Wang, J., Zhang, W., Wu, C. and Yang, J. 2014. Pseudoginsenoside-F11 (PF11) exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1/IKK/NF-${\kappa}B$, MAPKs and Akt signaling pathways. Neuropharmacology 79, 642-656. https://doi.org/10.1016/j.neuropharm.2014.01.022
  28. Yim, M. J., Lee, J. M., Choi, G., Lee, D. S., Park, W. S., Jung, W. K., Park, S., Seo, S. K., Park, J., Choi, I. W. and Ma, S. Y. 2018. Anti-Inflammatory potential of Carpomitra costata ethanolic extracts via inhibition of NF-${\kappa}B$ and AP-1 activation in LPS-stimulated RAW264.7 macrophages. Evid. Based Complement. Alternat. Med. 2018, 6914514.
  29. Yoon, H. M., Jang, K. J., Han, M. S., Jeong, J. W., Kim, G. Y., Lee, J. H. and Choi, Y. H. 2013. Ganoderma lucidum ethanol extract inhibits the inflammatory response by suppressing the NF-${\kappa}B$ and toll-like receptor pathways in lipopolysaccharide-stimulated BV2 microglial cells. Exp. Ther. Med. 5, 957-963. https://doi.org/10.3892/etm.2013.895
  30. Zheng, J., Hewage, S. R., Piao, M. J., Kang, K. A., Han, X., Kang, H. K., Yoo, E. S., Koh, Y. S., Lee, N. H., Ko, C. S., Lee, J. C., Ko, M. H. and Hyun, J. W. 2016. Photoprotective effect of Carpomitra costata extract against ultraviolet B-induced oxidative damage in human keratinocytes. J. Environ. Pathol. Toxicol. Oncol. 35, 11-28. https://doi.org/10.1615/JEnvironPatholToxicolOncol.2016014003