Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-neuroinflammatory effects of ethanolic extract of black chokeberry (Aronia melanocapa L.) in lipopolysaccharide-stimulated BV2 cells and ICR mice

  • Lee, Kang Pa (Department of Physiology, School of Medicine, Konkuk University) ;
  • Choi, Nan Hee (Department of Biotechnology, College of Engineering, Daegu University) ;
  • Kim, Hyun-Soo (Department of Marine Life Science, Jeju National University) ;
  • Ahn, Sanghyun (Department of Anatomy, College of Korean Medicine, Semyung University) ;
  • Park, In-Sik (Department of Anatomy, College of Korean Medicine, Dongguk University) ;
  • Lee, Dea Won (Department of Bio-Science, College of Natural Science, Dongguk University)
  • Received : 2017.08.09
  • Accepted : 2017.11.07
  • Published : 2018.02.01
Download PDF
⟨ Previous Next ⟩

Abstract

BACKGROUND/OBJECTIVES: One of the mechanisms considered to be prevalent in the development of Alzheimer's disease (AD) is hyper-stimulation of microglia. Black chokeberry (Aronia melanocapa L.) is widely used to treat diabetes and atherosclerosis, and is known to exert anti-oxidant and anti-inflammatory effects; however, its neuroprotective effects have not been elucidated thus far. MATERIALS/METHODS: We undertook to assess the anti-inflammatory effect of the ethanolic extract of black chokeberry friut (BCE) in BV2 cells, and evaluate its neuroprotective effect in the lipopolysaccharide (LPS)-induced mouse model of AD. RESULTS: Following stimulation of BV2 cells by LPS, exposure to BCE significantly reduced the generation of nitric oxide as well as mRNA levels of numerous inflammatory factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta ($IL-1{\beta}$), and tumor necrosis factor alpha ($TNF-{\alpha}$). In addition, AD was induced in a mouse model by intraperitoneal injection of LPS ($250{\mu}g/kg$), subsequent to which we investigated the neuroprotective effects of BCE (50 mg/kg) on brain damage. We observed that BCE significantly reduced tissue damage in the hippocampus by downregulating iNOS, COX-2, and $TNF-{\alpha}$ levels. We further identified the quinic acids in BCE using liquid chromatography-mass spectrometry (LCMS). Furthermore, we confirmed the neuroprotective effect of BCE and quinic acid on amyloid beta-induced cell death in rat hippocampal primary neurons. CONCLUSIONS: Our findings suggest that black chokeberry has protective effects against the development of AD.

Keywords

References

  1. Obisesan TO, Gillum RF, Johnson S, Umar N, Williams D, Bond V, Kwagyan J. Neuroprotection and neurodegeneration in Alzheimer's disease: role of cardiovascular disease risk factors, implications for dementia rates, and prevention with aerobic exercise in African Americans. Int J Alzheimers Dis 2012;2012:568382.
  2. Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML. Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 2005;25:1904-13. https://doi.org/10.1523/JNEUROSCI.4540-04.2005
  3. Katzman R. Alzheimer's disease. N Engl J Med 1986;314:964-73. https://doi.org/10.1056/NEJM198604103141506
  4. Choonara YE, Pillay V, du Toit LC, Modi G, Naidoo D, Ndesendo VM, Sibambo SR. Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders. Int J Mol Sci 2009;10:2510-57. https://doi.org/10.3390/ijms10062510
  5. Murphy MP, LeVine H 3rd. Alzheimer's disease and the amyloid-beta peptide. J Alzheimers Dis 2010;19:311-23. https://doi.org/10.3233/JAD-2010-1221
  6. LaFerla FM, Green KN, Oddo S. Intracellular amyloid-beta in Alzheimer's disease. Nat Rev Neurosci 2007;8:499-509. https://doi.org/10.1038/nrn2168
  7. Zotova E, Nicoll JA, Kalaria R, Holmes C, Boche D. Inflammation in Alzheimer's disease: relevance to pathogenesis and therapy. Alzheimers Res Ther 2010;2:1. https://doi.org/10.1186/alzrt24
  8. Chen Z, Jalabi W, Shpargel KB, Farabaugh KT, Dutta R, Yin X, Kidd GJ, Bergmann CC, Stohlman SA, Trapp BD. Lipopolysaccharideinduced microglial activation and neuroprotection against experimental brain injury is independent of hematogenous TLR4. J Neurosci 2012;32:11706-15. https://doi.org/10.1523/JNEUROSCI.0730-12.2012
  9. Choi SK, Park YS, Choi DK, Chang HI. Effects of astaxanthin on the production of NO and the expression of COX-2 and iNOS in LPS-stimulated BV2 microglial cells. J Microbiol Biotechnol 2008;18:1990-6.
  10. Bamberger ME, Landreth GE. Microglial interaction with beta-amyloid: implications for the pathogenesis of Alzheimer's disease. Microsc Res Tech 2001;54:59-70. https://doi.org/10.1002/jemt.1121
  11. Lee CY, Landreth GE. The role of microglia in amyloid clearance from the AD brain. J Neural Transm (Vienna) 2010;117:949-60. https://doi.org/10.1007/s00702-010-0433-4
  12. Nimmervoll B, White R, Yang JW, An S, Henn C, Sun JJ, Luhmann HJ. LPS-induced microglial secretion of $TNF{\alpha}$ increases activitydependent neuronal apoptosis in the neonatal cerebral cortex. Cereb Cortex 2013;23:1742-55. https://doi.org/10.1093/cercor/bhs156
  13. Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease. Ann Transl Med 2015;3:136.
  14. Dai Q, Borenstein AR, Wu Y, Jackson JC, Larson EB. Fruit and vegetable juices and Alzheimer's disease: the Kame Project. Am J Med 2006;119:751-9. https://doi.org/10.1016/j.amjmed.2006.03.045
  15. Mao J, Huang S, Liu S, Feng XL, Yu M, Liu J, Sun YE, Chen G, Yu Y, Zhao J, Pei G. A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation. Aging Cell 2015;14:784-96. https://doi.org/10.1111/acel.12356
  16. Dragan S, Andrica F, Serban MC, Timar R. Polyphenols-rich natural products for treatment of diabetes. Curr Med Chem 2015;22:14-22.
  17. Zapolska-Downar D, Bryk D, Malecki M, Hajdukiewicz K, Sitkiewicz D. Aronia melanocarpa fruit extract exhibits anti-inflammatory activity in human aortic endothelial cells. Eur J Nutr 2012;51:563-72. https://doi.org/10.1007/s00394-011-0240-1
  18. Jurikova T, Mlcek J, Skrovankova S, Sumczynski D, Sochor J, Hlavacova I, Snopek L, Orsavova J. Fruits of black chokeberry aronia melanocarpa in the prevention of chronic diseases. Molecules 2017;22:E944. https://doi.org/10.3390/molecules22060944
  19. Lee KP, Kim JE, Park WH. Cytoprotective effect of rhamnetin on miconazole-induced H9c2 cell damage. Nutr Res Pract 2015;9:586-91. https://doi.org/10.4162/nrp.2015.9.6.586
  20. Paulrayer A, Adithan A, Lee JH, Moon KH, Kim DG, Im SY, Kang CW, Kim NS, Kim JH. Aronia melanocarpa (black chokeberry) reduces ethanol-induced gastric damage via regulation of HSP-70, $NF-{\kappa}B $, and MCP-1 signaling. Int J Mol Sci 2017;18:E1195. https://doi.org/10.3390/ijms18061195
  21. Lee KP, Choi NH, Sudjarwo GW, Ahn SH, Park IS, Lee SR, Hong H. Protective effect of areca catechu leaf ethanol extract against ethanolinduced gastric ulcers in ICR mice. J Med Food 2016;19:127-32. https://doi.org/10.1089/jmf.2015.3476
  22. Gasparini L, Rusconi L, Xu H, del Soldato P, Ongini E. Modulation of beta-amyloid metabolism by non-steroidal anti-inflammatory drugs in neuronal cell cultures. J Neurochem 2004;88:337-48.
  23. Lee JW, Lee YK, Yuk DY, Choi DY, Ban SB, Oh KW, Hong JT. Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J Neuroinflammation 2008;5:37. https://doi.org/10.1186/1742-2094-5-37
  24. Yan Q, Zhang J, Liu H, Babu-Khan S, Vassar R, Biere AL, Citron M, Landreth G. Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer's disease. J Neurosci 2003;23:7504-9.
  25. Granado-Lorencio F, Hernandez-Alvarez E. Functional foods and health effects: a nutritional biochemistry perspective. Curr Med Chem 2016;23:2929-57. https://doi.org/10.2174/0929867323666160615105746
  26. Aronson JK. Defining 'nutraceuticals': neither nutritious nor pharmaceutical. Br J Clin Pharmacol 2017;83:8-19. https://doi.org/10.1111/bcp.12935
  27. Asiimwe N, Yeo SG, Kim MS, Jung J, Jeong NY. Nitric oxide: exploring the contextual link with Alzheimer's disease. Oxid Med Cell Longev 2016;2016:7205747.
  28. Danysz W, Parsons CG. Alzheimer's disease, ${\beta}$-amyloid, glutamate, NMDA receptors and memantine--searching for the connections. Br J Pharmacol 2012;167:324-52. https://doi.org/10.1111/j.1476-5381.2012.02057.x
  29. Selkoe DJ. Alzheimer's disease is a synaptic failure. Science 2002;298:789-91. https://doi.org/10.1126/science.1074069
  30. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med 2016;8:595-608. https://doi.org/10.15252/emmm.201606210
  31. Pero RW, Lund H, Leanderson T. Antioxidant metabolism induced by quinic acid. Increased urinary excretion of tryptophan and nicotinamide. Phytother Res 2009;23:335-46. https://doi.org/10.1002/ptr.2628

Cited by

  1. Smallanthus sonchifolius leaf attenuates neuroinflammation vol.22, pp.2, 2018, https://doi.org/10.20463/jenb.2018.0014
  2. Effect of black chokeberry on skeletal muscle damage and neuronal cell death vol.23, pp.4, 2018, https://doi.org/10.20463/jenb.2019.0028
  3. Effect of Korean Magnolia obovata Extract on Platelet-Derived Growth Factor-Induced Vascular Smooth Muscle Cells vol.26, pp.9, 2020, https://doi.org/10.1007/s11655-019-3171-y
  4. Evaluation of Antioxidant and Anti-Inflammatory Activity of Anthocyanin-Rich Water-Soluble Aronia Dry Extracts vol.25, pp.18, 2018, https://doi.org/10.3390/molecules25184055
  5. Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice vol.11, pp.9, 2020, https://doi.org/10.1039/d0fo00946f
  6. Therapeutic effect of Shinkiwhan, herbal medicine, regulates OPG/RANKL/RANK system on ovariectomy-induced bone loss rat vol.24, pp.3, 2018, https://doi.org/10.20463/pan.2020.0017
  7. The Efficacy of Black Chokeberry Fruits against Cardiovascular Diseases vol.22, pp.12, 2021, https://doi.org/10.3390/ijms22126541
  8. Black chokeberry (Aronia melanocarpa) extracts in terms of geroprotector criteria vol.114, pp.None, 2018, https://doi.org/10.1016/j.tifs.2021.06.020
  9. The efficacy of berries against lipopolysaccharide-induced inflammation: A review vol.117, pp.None, 2018, https://doi.org/10.1016/j.tifs.2021.01.015