DOI QR코드

DOI QR Code

Quinic Acid Alleviates Behavior Impairment by Reducing Neuroinflammation and MAPK Activation in LPS-Treated Mice

  • Yongun Park (College of Pharmacy, Chung-Ang University) ;
  • Yunn Me Me Paing (College of Pharmacy, Chung-Ang University) ;
  • Namki Cho (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University) ;
  • Changyoun Kim (Molecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health) ;
  • Jiho Yoo (College of Pharmacy, Chung-Ang University) ;
  • Ji Woong Choi (College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University) ;
  • Sung Hoon Lee (College of Pharmacy, Chung-Ang University)
  • 투고 : 2023.10.25
  • 심사 : 2023.12.27
  • 발행 : 2024.05.01

초록

Compared to other organs, the brain has limited antioxidant defenses. In particular, the hippocampus is the central region for learning and memory and is highly susceptible to oxidative stress. Glial cells are the most abundant cells in the brain, and sustained glial cell activation is critical to the neuroinflammation that aggravates neuropathology and neurotoxicity. Therefore, regulating glial cell activation is a promising neurotherapeutic treatment. Quinic acid (QA) and its derivatives possess anti-oxidant and anti-inflammatory properties. Although previous studies have evidenced QA's benefit on the brain, in vivo and in vitro analyses of its anti-oxidant and anti-inflammatory properties in glial cells have yet to be established. This study investigated QA's rescue effect in lipopolysaccharide (LPS)-induced behavior impairment. Orally administering QA restored social impairment and LPS-induced spatial and fear memory. In addition, QA inhibited proinflammatory mediator, oxidative stress marker, and mitogen-activated protein kinase (MAPK) activation in the LPS-injected hippocampus. QA inhibited nitrite release and extracellular signal-regulated kinase (ERK) phosphorylation in LPS-stimulated astrocytes. Collectively, QA restored impaired neuroinflammation-induced behavior by regulating proinflammatory mediator and ERK activation in astrocytes, demonstrating its potential as a therapeutic agent for neuroinflammation-induced brain disease treatments.

키워드

과제정보

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT) (Grant No. 2020R1C1C1008852, 2021R1C1C1012076, 2021M3E5E3080529, and 2021R1A6A1A0304429).

참고문헌

  1. Bajda, M., Guzior, N., Ignasik, M. and Malawska, B. (2011) Multi-target-directed ligands in Alzheimer's disease treatment. Curr. Med. Chem. 18, 4949-4975. https://doi.org/10.2174/092986711797535245
  2. Bin Saifullah, M. A., Nagai, T., Kuroda, K., Wulaer, B., Nabeshima, T., Kaibuchi, K. and Yamada, K. (2018) Cell type-specific activation of mitogen-activated protein kinase in D1 receptor-expressing neurons of the nucleus accumbens potentiates stimulus-reward learning in mice. Sci. Rep. 8, 14413.
  3. Bu, X. N., Huang, P., Qi, Z. F., Zhang, N., Han, S., Fang, L. and Li, J. F. (2007) Cell type-specific activation of p38 MAPK in the brain regions of hypoxic preconditioned mice. Neurochem. Int. 51, 459-466. https://doi.org/10.1016/j.neuint.2007.04.028
  4. Calabrese, V., Mancuso, C., Calvani, M., Rizzarelli, E., Butterfield, D. A. and Stella, A. M. G. (2007) Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat. Rev. Neurosci. 8, 766-775. https://doi.org/10.1038/nrn2214
  5. Chan, E. D. and Riches, D. W. H. (2001) IFN-γ+LPS induction of iNOS is modulated by ERK, JNK/SAPK, and p38 in a mouse macrophage cell line. Am. J. Physiol. Cell Physiol. 280, C441-C450. https://doi.org/10.1152/ajpcell.2001.280.3.C441
  6. Chitnis, T. and Weiner, H. L. (2017) CNS inflammation and neurodegeneration. J. Clin. Invest. 127, 3577-3587. https://doi.org/10.1172/JCI90609
  7. Ferruzzi, M. G., Lobo, J. K., Janle, E. M., Cooper, B., Simon, J. E., Wu, Q. L., Welch, C., Ho, L., Weaver, C. and Pasinetti, G. M. (2009) Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimer's disease. J. Alzheimers Dis. 18, 113-124. https://doi.org/10.3233/JAD-2009-1135
  8. 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
  9. Halliwell, B. (2006) Oxidative stress and neurodegeneration: where are we now? J. Neurochem. 97, 1634-1658. https://doi.org/10.1111/j.1471-4159.2006.03907.x
  10. Huang, T. T., Leu, D. and Zou, Y. (2015) Oxidative stress and redox regulation on hippocampal-dependent cognitive functions. Arch. Biochem. Biophys. 576, 2-7. https://doi.org/10.1016/j.abb.2015.03.014
  11. Jantan, I., Ahmad, W. and Bukhari, S. N. A. (2015) Plant-derived immunomodulators: an insight on their preclinical evaluation and clinical trials. Front. Plant Sci. 6, 655.
  12. Kameyama, T., Nabeshima, T. and Kozawa, T. (1986) Step-down-type passive avoidance-learning and escape-learning method - suitability for experimental amnesia models. J. Pharmacol. Method 16, 39-52. https://doi.org/10.1016/0160-5402(86)90027-6
  13. Kim, S. H. and Shin, T. Y. (2006) Effect of Dracocephalum argunense on mast-cell-mediated hypersensitivity. Int. Arch. Allergy Immunol. 139, 87-95. https://doi.org/10.1159/000090383
  14. Kim, S. R., Park, Y., Li, M., Kim, Y. K., Lee, S., Son, S. Y., Lee, S., Lee, J. S., Lee, C. H., Park, H. H., Lee, J. Y., Hong, S., Cho, Y. C., Kim, J. W., Yoo, H. M., Cho, N., Lee, H. S. and Lee, S. H. (2022) Anti-inflammatory effect of Ailanthus altissima (Mill.) Swingle leaves in lipopolysaccharide-stimulated astrocytes. J. Ethnopharmacol. 286, 114258.
  15. Koeberle, A. and Werz, O. (2014) Multi-target approach for natural products in inflammation. Drug Discov. Today 19, 1871-1882. https://doi.org/10.1016/j.drudis.2014.08.006
  16. Kumar, A. (2018) Editorial: neuroinflammation and cognition. Front. Aging Neurosci. 10, 413.
  17. Kwon, Y. K., Choi, S. J., Kim, C. R., Kim, J. K., Kim, Y. J., Choi, J. H., Song, S. W., Kim, C. J., Park, G. G., Park, C. S. and Shin, D. H. (2016) Antioxidant and cognitive-enhancing activities of Arctium lappa L. roots in A beta(1-42)-induced mouse model. Appl. Biol. Chem. 59, 553-565. https://doi.org/10.1007/s13765-016-0195-2
  18. Lee, K. P., Choi, N. H., Kim, H. S., Ahn, S., Park, I. S. and Lee, D. W. (2018) Anti-neuroinflammatory effects of ethanolic extract of black chokeberry (Aronia melanocapa L.) in lipopolysaccharide-stimulated BV2 cells and ICR mice. Nutr. Res. Pract. 12, 13-19. https://doi.org/10.4162/nrp.2018.12.1.13
  19. Lim, D. W., Park, J., Jung, J., Kim, S. H., Um, M. Y., Yoon, M., Kim, Y. T., Han, D., Lee, C. and Lee, J. (2020) Dicaffeoylquinic acids alleviate memory loss via reduction of oxidative stress in stress-hormone-induced depressive mice. Pharmacol. Res. 161, 105252.
  20. Liu, L., Liu, Y., Zhao, J., Xing, X., Zhang, C. and Meng, H. (2020) Neuroprotective effects of D-(-)-quinic acid on aluminum chloride-induced dementia in rats. Evid. Based Complement. Alternat. Med. 2020, 5602597.
  21. Liu, T. T., Zhu, X. L., Huang, C. L., Chen, J., Shu, S., Chen, G. Q., Xu, Y. and Hu, Y. M. (2022) ERK inhibition reduces neuronal death and ameliorates inflammatory responses in forebrain-specific knockout mice. FASEB J. 36, e22515.
  22. Lu, X., Ma, L., Ruan, L., Kong, Y., Mou, H., Zhang, Z., Wang, Z., Wang, J. M. and Le, Y. (2010) Resveratrol differentially modulates inflammatory responses of microglia and astrocytes. J. Neuroinflammation 7, 46.
  23. Lucas, R. M., Luo, L. and Stow, J. L. (2022) ERK1/2 in immune signalling. Biochem. Soc. Trans. 50,1341-1352. https://doi.org/10.1042/BST20220271
  24. Park, J. S., Park, E. M., Kim, D. H., Jung, K., Jung, J. S., Lee, E. J., Hyun, J. W., Kang, J. L. and Kim, H. S. (2009) Anti-inflammatory mechanism of ginseng saponins in activated microglia. J. Neuroimmunol. 209, 40-49. https://doi.org/10.1016/j.jneuroim.2009.01.020
  25. Pittenger, C., Fasano, S., Mazzocchi-Jones, D., Dunnett, S. B., Kandel, E. R. and Brambilla, R. (2006) Impaired bidirectional synaptic plasticity and procedural memory formation in striatum-specific cAMP response element-binding protein-deficient mice. J. Neurosci. 26, 2808-2813. https://doi.org/10.1523/JNEUROSCI.5406-05.2006
  26. Rebai, O., Belkhir, M., Sanchez-Gomez, M. V., Matute, C., Fattouch, S. and Amri, M. (2017) Differential molecular targets for neuroprotective effect of chlorogenic acid and its related compounds against glutamate induced excitotoxicity and oxidative stress in rat cortical neurons. Neurochem. Res. 42, 3559-3572. https://doi.org/10.1007/s11064-017-2403-9
  27. Reynolds, A., Laurie, C., Mosley, R. L. and Gendelman, H. E. (2007) Oxidative stress and the pathogenesis of neurodegenerative disorders. Int. Rev. Neurobiol. 82, 297-325. https://doi.org/10.1016/S0074-7742(07)82016-2
  28. Saha, R. N. and Pahan, K. (2006) Signals for the induction of nitric oxide synthase in astrocytes. Neurochem. Int. 49, 154-163. https://doi.org/10.1016/j.neuint.2006.04.007
  29. Sandiego, C. M., Gallezot, J. D., Pittman, B., Nabulsi, N., Lim, K., Lin, S. F., Matuskey, D., Lee, J. Y., O'Connor, K. C., Huang, Y., Carson, R. E., Hannestad, J. and Cosgrove, K. P. (2015) Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proc. Natl. Acad. Sci. U. S. A. 112, 12468-12473. https://doi.org/10.1073/pnas.1511003112
  30. von Bartheld, C. S., Bahney, J. and Herculano-Houzel, S. (2016) The search for true numbers of neurons and glial cells in the human brain: a review of 150 years of cell counting. J. Comp. Neurol. 524, 3865-3895. https://doi.org/10.1002/cne.24040
  31. Wang, Z. Q., Wu, D. C., Huang, F. P. and Yang, G. Y. (2004) Inhibition of MEK/ERK 1/2 pathway reduces pro-inflammatory cytokine interleukin-1 expression in focal cerebral ischemia. Brain Res. 996, 55-66. https://doi.org/10.1016/j.brainres.2003.09.074
  32. Zhang, G., He, J. L., Xie, X. Y. and Yu, C. (2012) LPS-induced iNOS expression in N9 microglial cells is suppressed by geniposide via ERK, p38 and nuclear factor-κB signaling pathways. Int. J. Mol. Med. 30, 561-568. https://doi.org/10.3892/ijmm.2012.1030
  33. Zhang, Y. J., Wu, L., Zhang, Q. L., Li, J., Yin, F. X. and Yuan, Y. (2011) Pharmacokinetics of phenolic compounds of Danshen extract in rat blood and brain by microdialysis sampling. J. Ethnopharmacol. 136, 129-136. https://doi.org/10.1016/j.jep.2011.04.023
  34. Zhao, J., Bi, W., Xiao, S., Lan, X., Cheng, X., Zhang, J., Lu, D., Wei, W., Wang, Y., Li, H., Fu, Y. and Zhu, L. (2019) Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Sci. Rep. 9, 5790.