Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
권호 표지
DOI QR코드

DOI QR Code

Ameliorative effect of onion (Allium Cepa L.) flesh and peel on amyloid-β-induced cognitive dysfunction via mitochondrial activation

미토콘드리아 활성화를 통한 양파(Allium Cepa L.) 과육 및 과피의 Amyloid-β 유도성 인지손상에 대한 개선효과

  • Park, Seon Kyeong (Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Lee, Uk (Division of Special Forest Products, National Institute of Forest Science) ;
  • Kang, Jin Yong (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) ;
  • Shin, Eun Jin (Division of Applied Life Science (BK21 Plus), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • 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) ;
  • 이욱 (국립산림과학원, 산림소득자원연구과) ;
  • 강진용 (경상대학교 응용생명과학부(BK21 plus), 농업생명과학연구원) ;
  • 김종민 (경상대학교 응용생명과학부(BK21 plus), 농업생명과학연구원) ;
  • 신은진 (경상대학교 응용생명과학부(BK21 plus), 농업생명과학연구원) ;
  • 허호진 (경상대학교 응용생명과학부(BK21 plus), 농업생명과학연구원)
  • Received : 2020.04.07
  • Accepted : 2020.05.05
  • Published : 2020.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, in order to confirm the ameliorative effects of onion (Allium cepa L.) flesh and peel on amyloidbeta (Aβ)-induced cognitive dysfunction, we evaluated their in vitro neuroprotection and in vivo cognitive functions. As the result of in vitro neuroprotection, the protective effect of the ethyl acetate fraction of onion flesh (EOF) on Aβ-induced cytotoxicity was similar to that of the ethyl acetate fraction of onion peel (EOP). In the behavioral tests, the EOF and EOP effectively improved the Aβ-induced learning and memory impairments. For this reason, it could be concluded that the EOF and EOP improved the antioxidant activities (superoxide dismutase, oxidized glutathione/total glutathione, and malondialdehyde) in brain tissue. In addition, the EOF and EOP effectively activated mitochondrial functions by protecting the mitochondrial membrane potential, ATP, mitochondria-mediated protein (BAX and cytochrome c), and caspase 3/7 activities. The EOF and EOP also improved the cholinergic system (acetylcholinesterase and acetylcholine). Therefore, we suggest that onion could be used for management of Aβ-induced cognitive dysfunction.

본 연구에서는 양파(Allium Cepa L.) 과육과 과피를 이용하여 in vitro 신경세포 보호효과 및 Aβ로 유도된 인지기능 장애 마우스 모델에서의 개선효과를 검증하고자 하였다. 양파 과육 분획물(EOF)과 과피 분획물(EOP) 모두 PC-12 세포에서 Aβ로 유도된 세포 독성에 대하여 신경세포 보호효과(세포 내 산화적 스트레스 억제, 세포 생존율 및 세포막 보호효과)를 나타냈다. Aβ로 유도된 인지장애 마우스 모델에서의 행동실험(Y-미로, 수동회피 및 Morris 수중 미로 시험) 결과 또한 양파 과육 분획물(EOF)과 과피 분획물(EOP) 모두 효과적인으로 학습 및 기억능력을 개선시키는 것으로 나타났다. 행동실험 후 마우스 뇌조직에서의 산화적 스트레스에 대한 생체 방어 기작의 일종인 SOD 함량의 증가, oxidized GSH/총 GSH 및 MDA 함량 감소를 나타냄에 따라 산화적 스트레스에 대한 우수한 항산화효과가 긍정적인 영향을 미친 것으로 판단된다. 또한, 뇌조직으로부터 분리한 미토콘드리아에 대하여 막 전위(MMP) 보호 및 ATP 함량 증가를 나타냈으며, 미토콘드리아와 관련된 apoptosis 경로에서 BAX의 감소 및 cytochrome c 방출 억제를 통해 caspase 3/7의 활성을 억제하는 것으로도 나타났다. 결국, 양파 과육 분획물(EOF)과 과피 분획물(EOP)은 AChE의 활성 억제 및 ACh의 함량을 증가시킴으로써 효과적인 콜린성 시스템 보호효과를 나타냄에 따라, Aβ로 유도된 인지기능 장애를 예방할 수 있는 고부가가치 건강기능식품 소재로의 활용 가능성이 기대된다.

Keywords

References

  1. Corzo-Martnez M, Corzo N, Villamiel M. Biological properties of onions and garlic. Trends Food Sci. Technol. 18: 609-625 (2007) https://doi.org/10.1016/j.tifs.2007.07.011
  2. Dong GZ, Lee JH, Ki SH, Yang JH, Cho IJ, Kang SH, Zhao RJ, Kim SC, Kim YW. AMPK activation by isorhamnetin protects hepatocytes against oxidative stress and mitochondrial dysfunction. Eur. J. Pharmacol. 740: 634-640 (2014) https://doi.org/10.1016/j.ejphar.2014.06.017
  3. Ellman GL, Courtney KD, Andres VJ, Featherstone RMA. New and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7: 88-90 (1961) https://doi.org/10.1016/0006-2952(61)90145-9
  4. Ferrer PE, Frederick P, Gulbis JM, Dewson G, Kluck RM. Translocation of a Bak C-terminus mutant from cytosol to mitochondria to mediate cytochrome c release: implications for Bak and Bax apoptotic function. PLoS One 7: 10.1371/journal.pone.0031510 (2012)
  5. Gupta R, Shukla RK, Chandravanshi LP, Srivastava P, Dhuriya YK, Shanker J, Singh MP, Pant AB, Khanna VK. Protective role of quercetin in cadmium-induced cholinergic dysfunctions in rat brain by modulating mitochondrial integrity and MAP kinase signaling. Mol. Neurobiol. 54: 4560-4583 (2017) https://doi.org/10.1007/s12035-016-9950-y
  6. Ha JS, Kim JM, Park SK, Kang JY, Lee U, Kim DO, Choi SG, Heo HJ. Anti-amyloidogenic properties of an ethyl acetate fraction from Actinidia arguta in $A{\beta}_{1-42}$-induced ICR mice. Food Func. 9: 3264-3277 (2018) https://doi.org/10.1039/C8FO00287H
  7. Henagan TM, Cefalu WT, Ribnicky DM, Noland RC, Dunville K, Campbell WW, Stewart LK, Forney LA, Gettys TW, Chang JS, Morrison CD. In vivo effects of dietary quercetin and quercetin-rich red onion extract on skeletal muscle mitochondria, metabolism, and insulin sensitivity. Genes Nutr. 10: 10.1007/s12263-014-0451-1 (2015)
  8. Ho SC, Liu JH, Wu RY. Establishment of the mimetic aging effect in mice caused by D-galactose. Biogerontology 4: 15-18 (2003) https://doi.org/10.1023/A:1022417102206
  9. Jan A, Hartley DM, Lashuel HA. Preparation and characterization of toxic $A{\beta}$ aggregates for structural and functional studies in Alzheimer's disease research. Nat. Protoc. 5: 1186-1209 (2010) https://doi.org/10.1038/nprot.2010.72
  10. Jin SL, Yin YG. In vivo antioxidant activity of total flavonoids from indocalamus leaves in aging mice caused by D-galactose. Food Chem. Toxicol. 50: 3814-3818 (2012) https://doi.org/10.1016/j.fct.2012.07.046
  11. Ma Y, Ma B, Shang Y, Yin Q, Hong Y, Xu S. Shen C, Hou X, Liu X. Flavonoid-rich ethanol extract from the leaves of Diospyros kaki attenuates cognitive deficits, amyloid-beta production, oxidative stress, and neuroinflammation in APP/PS1 transgenic mice. Brain Res. 1678: 85-93 (2018) https://doi.org/10.1016/j.brainres.2017.10.001
  12. McComb S, Chan PK, Guinot A, Hartmannsdottir H, Jenni S, Dobay MP, Bourquin JP, Bornhauser BC. Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or -7. Sci. Adv. 5: 10.1126/sciadv.aau9433 (2019)
  13. Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J. Neurosci. Methods 11: 47-60 (1984) https://doi.org/10.1016/0165-0270(84)90007-4
  14. Morley JE, Farr SA. The role of amyloid-beta in the regulation of memory. Biochem. Pharmacol. 88: 479-485 (2014) https://doi.org/10.1016/j.bcp.2013.12.018
  15. Mesram N, Nagapuri K, Banala RR, Nalagoni CR, Karnati PR. Quercetin treatment against NaF induced oxidative stress related neuronal and learning changes in developing rats. J. King Saud Univ. Sci. 29: 221-229 (2017) https://doi.org/10.1016/j.jksus.2016.04.002
  16. Pagani L, Eckert A. Amyloid-Beta interaction with mitochondria. J. Alzheimers Dis. 2011: Article ID 925050 (2011)
  17. Park SK, Jin DE, Park CH, Seung TW, Guoa TJ, Choi SG, Heo HJ. 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 (2015a) https://doi.org/10.14397/jals.2015.49.2.83
  18. Park SK, Jin DE, Park CH, Seung TW, Guo TJ, Song JW, Kim JH, Kim DO, Heo HJ. 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 (2015b) https://doi.org/10.1016/j.foodres.2015.05.038
  19. Presnell CE, Bhatti G, Numan LS, Lerche M, Alkhateeb SK, Ghalib M, Shammaa M, Kavdia M. Computational insights into the role of glutathione in oxidative stress. Curr. Neurovasc. Res. 10: 185-194 (2013) https://doi.org/10.2174/1567202611310020011
  20. Price KR, Bacon JR, Rhodes MJ. Effect of storage and domestic processing on the content and composition of flavonol glucosides in onion (Allium cepa). J. Agric. Food Chem. 45: 938-942 (1997) https://doi.org/10.1021/jf9605916
  21. Pun PB, Lu JIA, Moochhala S. Involvement of ROS in BBB dysfunction. Free Radic. Res. 43: 348-364 (2009) https://doi.org/10.1080/10715760902751902
  22. Reddy PH, Beal MF. Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends Mol. Med. 14: 45-53 (2008) https://doi.org/10.1016/j.molmed.2007.12.002
  23. Shon MY, Choi SD, Kahng GG, Nam SH, Sung NJ. Antimutagenic, antioxidant and free radical scavenging activity of ethyl acetate extracts from white, yellow and red onions. Food Chem. Toxicol. 42: 659-666 (2004) https://doi.org/10.1016/j.fct.2003.12.002
  24. Sorrentino V, Romani M, Mouchiroud L, Beck JS, Zhang H, D'amico D, Moullan N, Potenza F, Schmid AW, Rietsch S, Counts SE, Auwerx J. Enhancing mitochondrial proteostasis reduces amyloid-${\beta}$ proteotoxicity. Nature 552: 10.1038/nature25143 (2017)
  25. Sullivan PG, Brown MR. Mitochondrial aging and dysfunction in Alzheimer's disease. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 29: 407-410 (2005) https://doi.org/10.1016/j.pnpbp.2004.12.007
  26. Vincent D, Segonzac G, Vincent MC. Colorimetric determination of acetylcholine by the hestrin hydroxylamine reaction and its application in pharmacy. Ann. Pharm. Fr. 16: 179-185 (1958)
  27. Wang DM, Li SQ, Wu WL, Zhu XY, Wang Y, Yuan HY. 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 (2014) https://doi.org/10.1007/s11064-014-1343-x
  28. Zeman S, Lloyd C, Meldrum B, Leigh PN. Excitatory amino acid, free radicals and the pathogenesis of motor neuron disease. Neuro. Appl. Neurobiol. 20: 219-231 (1994) https://doi.org/10.1111/j.1365-2990.1994.tb00963.x
  29. Zhang X, Hu J, Zhong L, Wang N, Yang L, Liu CC, Li H, Wang X, Zhou Y, Zhang Y, Xu H, Bu G, Zhuang Z. Quercetin stabilizes apolipoprotein E and reduces brain $A{\beta}$ levels in amyloid model mice. Neuropharmacology 108: 179-192 (2016) https://doi.org/10.1016/j.neuropharm.2016.04.032