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Comparison of the effect of three licorice varieties on cognitive improvement via an amelioration of neuroinflammation in lipopolysaccharide-induced mice

  • Cho, Min Ji (Department of Food Science and Nutrition, Pusan National University) ;
  • Kim, Ji Hyun (Department of Food Science and Nutrition, Pusan National University) ;
  • Park, Chan Hum (Department of Herbal Crop Research, NIHHS, RDA) ;
  • Lee, Ah Young (Department of Food Science and Nutrition, Pusan National University) ;
  • Shin, Yu Su (Department of Herbal Crop Research, NIHHS, RDA) ;
  • Lee, Jeong Hoon (Department of Herbal Crop Research, NIHHS, RDA) ;
  • Park, Chun Geun (Department of Herbal Crop Research, NIHHS, RDA) ;
  • Cho, Eun Ju (Department of Food Science and Nutrition, Pusan National University)
  • Received : 2017.11.20
  • Accepted : 2018.02.08
  • Published : 2018.06.01

Abstract

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

Keywords

References

  1. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement 2007;3:186-91. https://doi.org/10.1016/j.jalz.2007.04.381
  2. Price JL, Morris JC. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease. Ann Neurol 1999;45:358-68. https://doi.org/10.1002/1531-8249(199903)45:3<358::AID-ANA12>3.0.CO;2-X
  3. Butterfield DA. Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic Res 2002;36:1307-13. https://doi.org/10.1080/1071576021000049890
  4. Canevari L, Abramov AY, Duchen MR. Toxicity of amyloid beta peptide: tales of calcium, mitochondria, and oxidative stress. Neurochem Res 2004;29:637-50. https://doi.org/10.1023/B:NERE.0000014834.06405.af
  5. Butterfield DA, Griffin S, Munch G, Pasinetti GM. Amyloid betapeptide and amyloid pathology are central to the oxidative stress and inflammatory cascades under which Alzheimer's disease brain exists. J Alzheimers Dis 2002;4:193-201. https://doi.org/10.3233/JAD-2002-4309
  6. DeLegge MH, Smoke A. Neurodegeneration and inflammation. Nutr Clin Pract 2008;23:35-41. https://doi.org/10.1177/011542650802300135
  7. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammationinduced death. Cell 2009;137:47-59. https://doi.org/10.1016/j.cell.2009.01.038
  8. Lukiw WJ. Bacteroides fragilis lipopolysaccharide and inflammatory signaling in Alzheimer's disease. Front Microbiol 2016;7:1544.
  9. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 2007;55:453-62. https://doi.org/10.1002/glia.20467
  10. Rosi S, Vazdarjanova A, Ramirez-Amaya V, Worley PF, Barnes CA, Wenk GL. Memantine protects against LPS-induced neuroinflammation, restores behaviorally-induced gene expression and spatial learning in the rat. Neuroscience 2006;142:1303-15. https://doi.org/10.1016/j.neuroscience.2006.08.017
  11. Hanke ML, Kielian T. Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin Sci (Lond) 2011;121:367-87. https://doi.org/10.1042/CS20110164
  12. Cafe-Mendes CC, Garay-Malpartida HM, Malta MB, de Sa Lima L, Scavone C, Ferreira ZS, Markus RP, Marcourakis T. Chronic nicotine treatment decreases LPS signaling through NF-${\kappa}B$ and TLR-4 modulation in the hippocampus. Neurosci Lett 2017;636:218-24. https://doi.org/10.1016/j.neulet.2016.10.056
  13. Ray B, Lahiri DK. Neuroinflammation in Alzheimer's disease: different molecular targets and potential therapeutic agents including curcumin. Curr Opin Pharmacol 2009;9:434-44. https://doi.org/10.1016/j.coph.2009.06.012
  14. Jain NK, Patil CS, Kulkarni SK, Singh A. Modulatory role of cyclooxygenase inhibitors in aging- and scopolamine or lipopolysaccharideinduced cognitive dysfunction in mice. Behav Brain Res 2002;133: 369-76. https://doi.org/10.1016/S0166-4328(02)00025-6
  15. Liao WC, Lin YH, Chang TM, Huang WY. Identification of two licorice species, Glycyrrhiza uralensis and Glycyrrhiza glabra, based on separation and identification of their bioactive components. Food Chem 2012;132:2188-93. https://doi.org/10.1016/j.foodchem.2011.12.051
  16. Hosseinzadeh H, Nassiri-Asl M. Pharmacological effects of Glycyrrhiza spp. and its bioactive constituents: update and review. Phytother Res 2015;29:1868-86. https://doi.org/10.1002/ptr.5487
  17. Yang R, Yuan BC, Ma YS, Zhou S, Liu Y. The anti-inflammatory activity of licorice, a widely used Chinese herb. Pharm Biol 2017; 55:5-18. https://doi.org/10.1080/13880209.2016.1225775
  18. Barfod L, Kemp K, Hansen M, Kharazmi A. Chalcones from Chinese liquorice inhibit proliferation of T cells and production of cytokines. Int Immunopharmacol 2002;2:545-55. https://doi.org/10.1016/S1567-5769(01)00202-8
  19. Yo YT, Shieh GS, Hsu KF, Wu CL, Shiau AL. Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway. J Agric Food Chem 2009;57:8266-73. https://doi.org/10.1021/jf901054c
  20. Lee HK, Yang EJ, Kim JY, Song KS, Seong YH. Inhibitory effects of Glycyrrhizae radix and its active component, isoliquiritigenin, on $A{\beta}$(25-35)-induced neurotoxicity in cultured rat cortical neurons. Arch Pharm Res 2012;35:897-904. https://doi.org/10.1007/s12272-012-0515-y
  21. Nomura T, Fukai T. Phenolic constituents of licorice (Glycyrrhiza species). Fortschr Chem Org Naturst 1998;73:1-158.
  22. Ojha S, Javed H, Azimullah S, Abul Khair SB, Haque ME. Glycyrrhizic acid attenuates neuroinflammation and oxidative stress in rotenone model of Parkinson's disease. Neurotox Res 2016;29:275-87. https://doi.org/10.1007/s12640-015-9579-z
  23. Cherng JM, Lin HJ, Hung MS, Lin YR, Chan MH, Lin JC. Inhibition of nuclear factor ${\kappa}B$ is associated with neuroprotective effects of glycyrrhizic acid on glutamate-induced excitotoxicity in primary neurons. Eur J Pharmacol 2006;547:10-21. https://doi.org/10.1016/j.ejphar.2006.06.080
  24. Song JH, Lee JW, Shim B, Lee CY, Choi S, Kang C, Sohn NW, Shin JW. Glycyrrhizin alleviates neuroinflammation and memory deficit induced by systemic lipopolysaccharide treatment in mice. Molecules 2013;18:15788-803. https://doi.org/10.3390/molecules181215788
  25. Akman T, Guven M, Aras AB, Ozkan A, Sen HM, Okuyucu A, Kalkan Y, Sehitoglu I, Silan C, Cosar M. The neuroprotective effect of glycyrrhizic acid on an experimental model of focal cerebral ischemia in rats. Inflammation 2015;38:1581-8. https://doi.org/10.1007/s10753-015-0133-1
  26. Guo J, Yang CX, Yang JJ, Yao Y. Glycyrrhizic acid ameliorates cognitive impairment in a rat model of vascular dementia associated with oxidative damage and inhibition of voltage-gated sodium channels. CNS Neurol Disord Drug Targets 2016;15:1001-8. https://doi.org/10.2174/1871527315666160527163526
  27. National Institute of Horticultural and Herbal Science (KR). 2014 Annual Reports. Wanju: National Institute of Horticultural and Herbal Science; 2014. p.58-9.
  28. Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique "guide drug" of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol 2013;150:781-90. https://doi.org/10.1016/j.jep.2013.09.055
  29. 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
  30. Gu SM, Park MH, Hwang CJ, Song HS, Lee US, Han SB, Oh KW, Ham YW, Song MJ, Son DJ, Hong JT. Bee venom ameliorates lipopolysaccharide-induced memory loss by preventing NF-kappaB pathway. J Neuroinflammation 2015;12:124. https://doi.org/10.1186/s12974-015-0344-2
  31. Montgomery KC. A test of two explanations of spontaneous alternation. J Comp Physiol Psychol 1952;45:287-93. https://doi.org/10.1037/h0058118
  32. Bevins RA, Besheer J. Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study 'recognition memory'. Nat Protoc 2006;1:1306-11. https://doi.org/10.1038/nprot.2006.205
  33. Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984;11:47-60. https://doi.org/10.1016/0165-0270(84)90007-4
  34. Montgomery KC. Exploratory behavior and its relation to spontaneous alternation in a series of maze exposures. J Comp Physiol Psychol 1952;45:50-7. https://doi.org/10.1037/h0053570
  35. Lee YJ, Choi DY, Choi IS, Kim KH, Kim YH, Kim HM, Lee K, Cho WG, Jung JK, Han SB, Han JY, Nam SY, Yun YW, Jeong JH, Oh KW, Hong JT. Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide- induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models. J Neuroinflammation 2012;9:35.
  36. Miwa M, Tsuboi M, Noguchi Y, Enokishima A, Nabeshima T, Hiramatsu M. Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2. J Neuroinflammation 2011;8:153.
  37. Sparkman NL, Martin LA, Calvert WS, Boehm GW. Effects of intraperitoneal lipopolysaccharide on Morris maze performance in year-old and 2-month-old female C57BL/6J mice. Behav Brain Res 2005;159:145-51. https://doi.org/10.1016/j.bbr.2004.10.011
  38. Sharifzadeh M, Shamsa F, Shiran S, Karimfar MH, Miri AH, Jalalizadeh H, Gholizadeh S, Salar F, Tabrizian K. A time course analysis of systemic administration of aqueous licorice extract on spatial memory retention in rats. Planta Med 2008;74:485-90. https://doi.org/10.1055/s-2008-1074494
  39. Dhingra D, Parle M, Kulkarni SK. Memory enhancing activity of Glycyrrhiza glabra in mice. J Ethnopharmacol 2004;91:361-5. https://doi.org/10.1016/j.jep.2004.01.016
  40. Rubio-Perez JM, Morillas-Ruiz JM. A review: inflammatory process in Alzheimer's disease, role of cytokines. ScientificWorldJournal 2012;2012:756357.
  41. Borowski T, Kokkinidis L, Merali Z, Anisman H. Lipopolysaccharide, central in vivo biogenic amine variations, and anhedonia. Neuroreport 1998;9:3797-801. https://doi.org/10.1097/00001756-199812010-00006
  42. Lukiw WJ, Bazan NG. Strong nuclear factor-kappaB-DNA binding parallels cyclooxygenase-2 gene transcription in aging and in sporadic Alzheimer's disease superior temporal lobe neocortex. J Neurosci Res 1998;53:583-92. https://doi.org/10.1002/(SICI)1097-4547(19980901)53:5<583::AID-JNR8>3.0.CO;2-5
  43. Thiyagarajan P, Chandrasekaran CV, Deepak HB, Agarwal A. Modulation of lipopolysaccharide-induced pro-inflammatory mediators by an extract of Glycyrrhiza glabra and its phytoconstituents. Inflammopharmacology 2011;19:235-41. https://doi.org/10.1007/s10787-011-0080-x
  44. Wu TY, Khor TO, Saw CL, Loh SC, Chen AI, Lim SS, Park JH, Cai L, Kong AN. Anti-inflammatory/Anti-oxidative stress activities and differential regulation of Nrf2-mediated genes by non-polar fractions of tea Chrysanthemum zawadskii and licorice Glycyrrhiza uralensis. AAPS J 2011;13:1-13. https://doi.org/10.1208/s12248-010-9239-4
  45. Schrofelbauer B, Raffetseder J, Hauner M, Wolkerstorfer A, Ernst W, Szolar OH. Glycyrrhizin, the main active compound in liquorice, attenuates pro-inflammatory responses by interfering with membranedependent receptor signalling. Biochem J 2009;421:473-82. https://doi.org/10.1042/BJ20082416
  46. Yu JY, Ha JY, Kim KM, Jung YS, Jung JC, Oh S. Anti-Inflammatory activities of licorice extract and its active compounds, glycyrrhizic acid, liquiritin and liquiritigenin, in BV2 cells and mice liver. Molecules 2015;20:13041-54. https://doi.org/10.3390/molecules200713041
  47. Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, Izquierdo I, Medina JH. BDNF is essential to promote persistence of long-term memory storage. Proc Natl Acad Sci U S A 2008;105:2711-6. https://doi.org/10.1073/pnas.0711863105
  48. Saura CA, Valero J. The role of CREB signaling in Alzheimer's disease and other cognitive disorders. Rev Neurosci 2011;22:153-69.
  49. Song JH, Yu JT, Tan L. Brain-derived neurotrophic factor in Alzheimer's disease: risk, mechanisms, and therapy. Mol Neurobiol 2015;52:1477-93. https://doi.org/10.1007/s12035-014-8958-4
  50. Schnydrig S, Korner L, Landweer S, Ernst B, Walker G, Otten U, Kunz D. Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain. Neurosci Lett 2007;429:69-73. https://doi.org/10.1016/j.neulet.2007.09.067

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