Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Onion Beverages Improve Amyloid β Peptide-Induced Cognitive Defects via Up-Regulation of Cholinergic Activity and Neuroprotection

양파(Allium cepa L.) 음료의 콜린성 활성 증가 및 뇌신경세포 보호로 인한 Amyloid β Peptide 유도에 대한 인지장애 개선 효과

  • Park, Seon Kyeong (Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Kim, Jong Min (Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Kang, Jin Yong (Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Ha, Jeong Su (Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Lee, Du Sang (Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Kim, Ah-Na (Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Choi, Sung-Gil (Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Lee, Uk (Division of Special Purpose Trees, National Institute of Forest Science) ;
  • Heo, Ho Jin (Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University)
  • 박선경 (경상대학교 응용생명과학부(BK21 Plus), 농업생명과학연구원) ;
  • 김종민 (경상대학교 응용생명과학부(BK21 Plus), 농업생명과학연구원) ;
  • 강진용 (경상대학교 응용생명과학부(BK21 Plus), 농업생명과학연구원) ;
  • 하정수 (경상대학교 응용생명과학부(BK21 Plus), 농업생명과학연구원) ;
  • 이두상 (경상대학교 응용생명과학부(BK21 Plus), 농업생명과학연구원) ;
  • 김아나 (경상대학교 응용생명과학부(BK21 Plus), 농업생명과학연구원) ;
  • 최성길 (경상대학교 응용생명과학부(BK21 Plus), 농업생명과학연구원) ;
  • 이욱 (국립산림과학원 특용자원연구과) ;
  • 허호진 (경상대학교 응용생명과학부(BK21 Plus), 농업생명과학연구원)
  • Received : 2016.07.11
  • Accepted : 2016.09.02
  • Published : 2016.11.30
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Abstract

To examine the cognitive function of onion (Allium cepa L.) beverages (odourless and fortified), we analyzed in vitro neuronal cell protection against $H_2O_2$-induced cytotoxicity and performed in vivo tests on amyloid beta ($A{\beta}$)-induced cognitive dysfunction. Cellular oxidative stress and cell viability were evaluated by DCF-DA assay and MTT assay. These results show that fortified beverage resulted in better neuronal cell protection than odourless beverage at lower concentration ($0{\sim}100{\mu}g/mL$). Fortified beverage also showed more excellent acetylcholinesterase (AChE) inhibitory activity ($IC_{50}$: 4.20 mg/mL) than odourless beverage. The cognitive functions of odourless beverage and fortified beverage in $A{\beta}$-induced neurotoxicity were assessed by Y-maze, passive avoidance, and Morris water maze tests. The results show improved cognitive function in both groups treated with beverages. After in vivo tests, cholinergic activities were determined based on AChE inhibition and acetylcholine levels, and antioxidant activities were measured as SOD, oxidized glutathione (GSH)/total GSH ratio, and MDA levels in mouse brain tissue. In a Q-TOF UPLC/MS system, main compounds were analyzed as follows: odourless beverage (five types of sugars and three types of phenolics) and fortified beverages (six types of phenolics and two types of steroidal saponins).

본 연구는 양파의 불쾌치를 저감화시킨 무취음료와 양파 과피 추출물을 첨가한 생리활성 성분 강화음료의 $H_2O_2$로 유도된 산화적 스트레스에 대한 뇌신경세포 보호 효과와 $A{\beta}$로 유도된 인지기능 장애 동물모델에서의 개선 효과를 검증하고자 수행되었다. 뇌신경세포 보호 효과에서는 상대적으로 강화음료에서 무취음료 대비 우수한 산화적 스트레스 억제효과 및 생존율을 나타내었다. $A{\beta}$로 유도된 인지기능 장애 동물모델에 있어 Y-maze, passive avoidance 및 Morris water maze test에서 강화음료가 상대적으로 우수한 학습 및 기억력 개선 효과를 나타내는 것을 확인할 수 있었다. 마우스의 뇌 조직에서 강화음료 그룹은 AChE 활성을 저해하고, 신경전달물질인 ACh의 함량을 증가시킴으로써 $A{\beta}$로 유도된 cholinergic system 장애에 있어 개선 효과를 나타내었다. 또한, 마우스 뇌에서 SOD 함량의 증가, oxidized GSH/total GSH와 MDA 함량을 감소시킴으로써 $A{\beta}$와 같은 산화적 스트레스 인자에 대한 뛰어난 항산화 효과를 나타내었다. 최종적으로 무취음료와 강화음료의 주요성분들을 Q-TOF UPLC/MS system을 통하여 분석한 결과, 강화음료의 경우 무취음료보다 생리활성을 가진 2개의 steroidal saponin과 6개의 phenolic 화합물 등이 추가 검출되었다. 이러한 결과들을 종합해볼 때 강화음료는 상대적으로 protocatechuic acid와 quercetin 같은 강력한 항산화 효과를 나타내는 phenolic 화합물과 steroidal saponin 계열에 의한 우수한 인지기능 개선 효과를 기반으로 한 고부가가치 식품으로 활용될 수 있는 산업적 가능성이 있다고 판단된다.

Keywords

References

  1. Choi SJ, Kim MJ, Heo HJ, Hong B, Cho HY, Kim YJ, Kim HK, Lim ST, Jun WJ, Kim EK, Shin DH. 2007. Ameliorating effect of Gardenia jasminoides extract on amyloid beta peptide-induced neuronal cell deficit. Mol Cells 24: 113-118.
  2. Alkam T, Nitta A, Mizoguchi H, Saito K, Seshima M, Itoh A, Yamada K, Nabeshima T. 2008. Restraining tumor necrosis factor-alpha by thalidomide prevents the amyloid beta-induced impairment of recognition memory in mice. Behav Brain Res 189: 100-106. https://doi.org/10.1016/j.bbr.2007.12.014
  3. Lu P, Mamiya T, Lu LL, Mouri A, Zou L, Nagai T, Hiramatsu M, Ikejima T, Nabeshima T. 2009. Silibinin prevents amyloid ${\beta}$ peptide-induced memory impairment and oxidative stress in mice. Br J Pharmacol 157: 1270-1277. https://doi.org/10.1111/j.1476-5381.2009.00295.x
  4. Maeda-Yamamoto M, Saito T, Nesumi A, Tokuda Y, Ema K, Honma D, Ogino A, Monobe M, Murakami A, Murakami A, Tachibana H. 2012. Chemical analysis and acetylcholinesterase inhibitory effect of anthocyanin-rich red leaf tea (cv. Sunrouge). J Sci Food Agric 92: 2379-2386. https://doi.org/10.1002/jsfa.5644
  5. Yoon MY, Lee BB, Kim JY, Kim Y, Park E, Lee SC, Park HR. 2007. Antioxidant activity and neuroprotective effect of Psoralea corylifolia Linne extracts. Kor J Pharmacogn 38: 84-89.
  6. Nijveldt RJ, van Nood E, van Hoorn DEC, Boelens PG, van Norren K, van Leeuwen PAM. 2001. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74: 418-425. https://doi.org/10.1093/ajcn/74.4.418
  7. Velioglu YS, Mazza G, Gao L, Oomah BD. 1998. Antioxidant activity and total phenolics in selected fruits, vegetables, and grain products. J Agric Food Chem 46: 4113-4117. https://doi.org/10.1021/jf9801973
  8. Kwon JH, Lee GD, Byun MW. 1999. Quality changes based on storage temperature and humidity of onion. Korean J Postharvest Sci Technol 6: 143-147.
  9. Corzo-Martinez M, Corzo N, Villamiel M. 2007. Biological properties of onions and garlic. Trends Food Sci Technol 18: 609-625. https://doi.org/10.1016/j.tifs.2007.07.011
  10. Park SK, Jin DE, Park CH, Seung TW, Guo TJ, Choi SG, Heo HJ. 2015. Antioxidant activity and PC12 cell protective effect of onion flesh and peel (Allium cepa L.) fraction on oxidative stress. J Agric Life Sci 49: 83-95. https://doi.org/10.14397/jals.2015.49.2.83
  11. Park SK, Jin DE, Park CH, Seung TW, Guo TJ, Song JW, Kim JH, Kim DO, Heo HJ. 2015. Ameliorating effects of ethyl acetate fraction from onion (Allium cepa L.) flesh and peel in mice following trimethyltin-induced learning and memory impairment. Food Res Int 75: 53-60. https://doi.org/10.1016/j.foodres.2015.05.038
  12. Moisio T, Spare CG, Virtanen AI. 1962. Mass spectral studies of the chemical nature of the lachrymatory factor formed enzymically from S-(1-propenyl)-cysteine sulfoxide isolated from onion (Allium cepa). Suom Kemistil B 35: 29.
  13. Virtanen AI, Spare CG. 1961. Isolation of the precursor of the lachrymatory factor in onion (Allium cepa). Suom Kemistil B 34: 72-74.
  14. Heo HJ, Cho HY, Hong B, Kim HK, Kim EK, Kim BG, Shin DH. 2001. Protective effect of 4',5-dihydroxy-3',6,7- trimethoxyflavone from Artemisia asiatica against $A{\beta}$-induced oxidative stress in PC12 cells. Amyloid 8: 194-201. https://doi.org/10.3109/13506120109007362
  15. Kim SS, Park RY, Jeon HJ, Kwon YS, Chun W. 2005. Neuroprotective effects of 3,5-dicaffeoylquinic acid on hydrogen peroxide-induced cell death in SH-SY5Y cells. Phytother Res 19: 243-245. https://doi.org/10.1002/ptr.1652
  16. Ellmans GL, Courtney KD, Andres V Jr, Featherstone RM. 1961. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7: 88-95. https://doi.org/10.1016/0006-2952(61)90145-9
  17. Morris R. 1984. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11: 47-60. https://doi.org/10.1016/0165-0270(84)90007-4
  18. Vincent A, Newsom-Davis J. 1985. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry 48: 1246-1252. https://doi.org/10.1136/jnnp.48.12.1246
  19. Yan JJ, Cho JY, Kim HS, Kim KL, Jung JS, Huh SO, Suh HW, Kim YH, Song DK. 2001. Protection against ${\beta}$-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. Br J Pharmacol 133: 89-96. https://doi.org/10.1038/sj.bjp.0704047
  20. Furuta A, Price DL, Pardo CA, Troncoso JC, Xu ZS, Taniguchi N, Martin LJ. 1995. Localization of superoxide dismutases in Alzheimer's disease and Down's syndrome neocortex and hippocampus. Am J Pathol 146: 357-367.
  21. Vina J, Lloret A, Orti R, Alonso D. 2004. Molecular bases of the treatment of Alzheimer’s disease with antioxidants: prevention of oxidative stress. Mol Aspects Med 25: 117-123. https://doi.org/10.1016/j.mam.2004.02.013
  22. Zhu J, Cole RB. 2001. Ranking of gas-phase acidities and chloride affinities of monosaccharides and linkage specificity in collision-induced decompositions of negative ion electrospray- generated chloride adducts of oligosaccharides. J Am Soc Mass Spectrom 12: 1193-1204. https://doi.org/10.1016/S1044-0305(01)00305-1
  23. Tulipani S, Huelamo MM, Ribalta MR, Estruch R, Ferrer EE, Andres-Lacueva C, Illan M, Lamuela-Raventós RM. 2012. Oil matrix effects on plasma exposure and urinary excretion of phenolic compounds from tomato sauces: Evidence from a human pilot study. Food Chem 130: 581-590. https://doi.org/10.1016/j.foodchem.2011.07.078
  24. Nagai A, Yamamoto T, Wariishi H. 2012. Identification of fructo- and malto-oligosaccharides in cured tobacco leaves (Nicotiana tabacum). J Agric Food Chem 60: 6606-6612. https://doi.org/10.1021/jf301395v
  25. Antonio C, Pinheiro C, Chaves MM, Ricardo CP, Ortuno MF, Thomas-Oates J. 2008. Analysis of carbohydrates in Lupinus albus stems on imposition of water deficit, using porous graphitic carbon liquid chromatography-electrospray ionization mass spectrometry. J Chromatogr A 1187: 111-118. https://doi.org/10.1016/j.chroma.2008.02.010
  26. Bantan T, Milacic R, Mitrovic B, Pihlar B. 1999. Investigation of low molecular weight Al complexes in human serum by fast protein liquid chromatography (FPLC)-ETAAS and electrospray (ES)-MS-MS techniques. J Anal At Spectrom 14: 1743-1748. https://doi.org/10.1039/A904213J
  27. Andlauer W, Martena MJ, Furst P. 1999. Determination of selected phytochemicals by reversed-phase high-performance liquid chromatography combined with ultraviolet and mass spectrometric detection. J Chromatogr A 849: 341-348. https://doi.org/10.1016/S0021-9673(99)00597-X
  28. Farias SE, Basselin M, Chang L, Heidenreich KA, Rapoport SI, Murphy RC. 2008. Formation of eicosanoids, E2/D2 isoprostanes, and docosanoids following decapitation-induced ischemia, measured in high-energy-microwaved rat brain. J Lipid Res 49: 1990-2000. https://doi.org/10.1194/jlr.M800200-JLR200
  29. Liu AH, Guo H, Ye M, Lin YH, Sun JH, Xu M, Guo DA. 2007. Detection, characterization and identification of phenolic acids in Danshen using high-performance liquid chromatography with diode array detection and electrospray ionization mass spectrometry. J Chromatogr A 1161: 170-182. https://doi.org/10.1016/j.chroma.2007.05.081
  30. Biesaga M, Pyrzynska K. 2009. Liquid chromatography/ tandem mass spectrometry studies of the phenolic compounds in honey. J Chromatogr A 1216: 6620-6626. https://doi.org/10.1016/j.chroma.2009.07.066
  31. Dou J, Lee VS, Tzen JT, Lee MR. 2007. Identification and comparison of phenolic compounds in the preparation of oolong tea manufactured by semifermentation and drying processes. J Agric Food Chem 55: 7462-7468. https://doi.org/10.1021/jf0718603
  32. Schieber A, Berardini N, Carle R. 2003. Identification of flavonol and xanthone glycosides from mango (Mangifera indica L. Cv. "Tommy Atkins") peels by high-performance liquid chromatography-electrospray ionization mass spectrometry. J Agric Food Chem 51: 5006-5011. https://doi.org/10.1021/jf030218f
  33. Zhang Y, Li HZ, Zhang YJ, Jacob MR, Khan SI, Li XC, Yang CR. 2006. Atropurosides A-G, new steroidal saponins from Smilacina atropurpurea. Steroids 71: 712-719. https://doi.org/10.1016/j.steroids.2006.04.005
  34. Xiaohui F, Yi W, Yiyu C. 2006. LC/MS fingerprinting of Shenmai injection: A novel approach to quality control of herbal medicines. J Pharm Biomed Anal 40: 591-597. https://doi.org/10.1016/j.jpba.2005.10.036
  35. Hausler M, Ganzera M, Abel G, Popp M, Stuppner H. 2002. Determination of caffeoylquinic acids and flavonoids in Cynara scolymus L. by high performance liquid chromatography. Chromatographia 56: 407-411. https://doi.org/10.1007/BF02492002
  36. Kwak JH, Choi GN, Park JH, Kim JH, Jeong HR, Jeong CH, Heo HJ. 2010. Antioxidant and neuronal cell protective effect of purple sweet potato extract. J Agric Life Sci 44: 57-66.
  37. Link KP, Angell HR, Walker JC. 1929. The isolation of protocatechuic acid from pigmented onion scales and its significance in relation to disease resistance in onions. J Biol Chem 81: 369-375.
  38. Kim JM, Park SK, Guo TJ, Kang JY, Ha JS, Lee DS, Lee U, Heo HJ. 2016. Anti-amnesic effect of Dendropanax morbifera via JNK signaling pathway on cognitive dysfunction in high-fat diet-induced diabetic mice. Behav Brain Res 312: 39-54. https://doi.org/10.1016/j.bbr.2016.06.013
  39. Wang DM, Li SQ, Wu WL, Zhu XY, Wang Y, Yuan HY. 2014. Effects of long-term treatment with quercetin on cognition and mitochondrial function in a mouse model of Alzheimer's disease. Neurochem Res 39: 1533-1543. https://doi.org/10.1007/s11064-014-1343-x
  40. Vitaglione P, Donnarumma G, Napolitano A, Galvano F, Gallo A, Scalfi L, Fogliano V. 2007. Protocatechuic acid is the major human metabolite of cyanidin-glucosides. J Nutr 137: 2043-2048. https://doi.org/10.1093/jn/137.9.2043
  41. Song Y, Cui T, Xie N, Zhang X, Qian Z, Liu J. 2014. Protocatechuic acid improves cognitive deficits and attenuates amyloid deposits, inflammatory response in aged $A{\beta}PP/PS1$ double transgenic mice. Int Immunopharmacol 20: 276-281. https://doi.org/10.1016/j.intimp.2014.03.006
  42. Back NI, Cho SJ, Bang MH, Lee L, Park C, Kim M, Kim K, Sung J. 1998. Cytotoxicity of steroid-saponins from the tuber of Liriope platyphylla W.T. Agric Chem Biotechnol 41: 390-384.
  43. Rhee IJ. 1997. Effect of Liriopis tuber extract on the decrease of blood glucose. Hoysung Bull Pharm Sci 2: 49-56.