Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
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Effect of 1,2,3,4,6-penta-O-gallolyl-β-ᴅ-glucose on markers of cognitive function in human neuroblastoma SK-N-SH cell line

1,2,3,4,6-Penta-O-gallolyl-β-ᴅ-glucose가 인간 유래 신경모세포주인 SK-N-SH세포의 인지기능 표지자에 미치는 영향

  • 윤현석 (대구대학교 식품영양학과) ;
  • 박소연 (대구대학교 식품영양학과) ;
  • 김윤희 (대구대학교 식품영양학과)
  • Received : 2021.09.10
  • Accepted : 2021.11.03
  • Published : 2021.12.31
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Abstract

Cognitive impairment and Alzheimer's disease are serious social problems associated with the rising elderly population in Korea. 1,2,3,4,6-Penta-O-galloyl-β-ᴅ-glucopyranose (PGG) is a gallotannin isolated from medicinal plants such as Rhus chinensis. This study was performed to evaluate the effect of PGG on biomarkers related to cognitive function in human neuroblastoma SK-N-SH cells. Inhibition of acetylcholinesterase (AChE) activity is considered to be one of the main therapeutic strategies. PGG inhibited AChE activity in the test tube as well as in SK-N-SH cells. In addition, PGG induced protein and mRNA expression of brain-derived neurotrophic factor (BDNF), which is a mammalian neurotrophin that plays major roles in the development, maintenance, repair, and survival of neuronal populations. As one of the underlying molecular mechanisms that induce BDNF expression, PGG induced the activation of Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII)-cAMP response element binding protein (CREB) pathway. In conclusion, PGG may be an useful material for improving cognitive function.

인구의 고령화에 따른 노인 인구 증가로 지난 10년간 치매환자수와 경도인지장애 환자수가 급증하였다. 치매는 예방이 중요한 만큼 인지기능 향상에 도움을 줄 수 있는 기능성 소재 탐색에 대한 연구가 필요하다. 한편, PGG는 다양한 약용식물에 함유되어있는 gallotannins로 소교세포에서 항염증효과, amyloid beta 단백질 침착 억제효과, beta-secretase 억제효과가 알려져 있으나 인지 기능과 관련된 지표들에 대한 연구는 부족한 실정이다. 이에 본 연구에서는 PGG가 신경모세포주인 SK-N-SH세포에서 인지기능과 관련된 인자에 미치는 영향을 검토하고 관련 기전에 대해 평가하였다. 퇴행성질환 등에서 그 분비가 증가되는 AChE 효소활성이 PGG 처리에 의해 시험관실험과 세포실험에서 모두 억제되었다. 또한, PGG는 neurotrophin 중의 하나인 BDNF mRNA 및 단백질 발현을 증가하였다. 이러한 PGG의 BDNF 발현 증가에 대한 분자적 기전을 확인하기 위해 CAMKII-CREB 신호경로를 측정한 결과, PGG는 CAMKII를 인산화하였고, BDNF의 전사인자인 CREB를 활성화하였다. 이상의 결과로부터, hydrolyzed tannins의 하나인 PGG가 신경세포에서 CAMKII-CREB 경로를 활성화함으로써 BDNF의 발현을 증가시킬 뿐만 아니라 AChE 활성을 억제하는 것으로 나타났다(Fig. 8). 추가적으로 이러한 PGG의 효과가 인지기능이 저하된 동물모델 등에서도 효과가 있는지를 검토할 필요가 있다. 이러한 자료가 축적이 된다면 향후 PGG가 인지기능 개선을 위한 기능성 소재로서의 사용될 가능성이 있을 것으로 생각된다.

Keywords

Acknowledgement

이 논문은 2018학년도 대구대학교 학술연구비지원(20180254)에 의한 논문으로 이에 감사드립니다.

References

  1. Abhijit D, Raktim B, Anuradha M, Devendra KP. Natural products against Alzheimer's disease: Pharmaco-therapeutics and biotechnological interventions. Biotechnol. Adv. 35: 178-216 (2017) https://doi.org/10.1016/j.biotechadv.2016.12.005
  2. Araki S, Osuka K, Takata T, Tsuchiya Y, Watanabe Y. Coordination between Calcium/Calmodulin-Dependent Protein Kinase II and Neuronal Nitric Oxide Synthase in Neurons. Int. J. Mol. Sci. 21: 7997 (2020) https://doi.org/10.3390/ijms21217997
  3. Barbacid M. Neurotrophic factors and their receptors. Curr. Opin. Cell Biol. 7: 148-155 (1995) https://doi.org/10.1016/0955-0674(95)80022-0
  4. Baek H, Chang GT, Kim JH. Experimental study on the effects of Bohyulanshin-tang on brain-derived neurotophic factor expression in SK-N-SH cell line. J. Physiol. Pathol. in Korean Med. 2: 139-145 (2005)
  5. Bekinschtein P, Cammarota M, Igaz LM, Bevilaqua LR, Izquierdo I, Medina JH. Persistence of long-term memory storage requires a late protein synthesis and BDNF-dependent phase in the hippocampus. Neuron. 53: 261-277 (2007) https://doi.org/10.1016/j.neuron.2006.11.025
  6. Briggs R, Kennelly SP, O'Neill D. Drug treatments in Alzheimer's disease. Clin. Med (Lond). 16: 247-253 (2016) https://doi.org/10.7861/clinmedicine.16-3-247
  7. Bruno LG, Janine D, Hans CK, Rudi AJOD, Elke B, Erik FJV. Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation. Mol. Neurobiol. 56: 3295-3312 (2019) https://doi.org/10.1007/s12035-018-1283-6
  8. Chen S, Jiang H, Liu Y, Hou Z, Yue Y, Zhang Y, et al. Combined serum levels of multiple proteins in tPA-BDNF pathway may aid the diagnosis of five mental disorders. Sci. Rep. 7: 6871 (2017) https://doi.org/10.1038/s41598-017-06832-6
  9. Corpuz HM, Fujii H, Nakamura S, Katayama S. Fermented rice peptides attenuate scopolamine-induced memory impairment in mice by regulating neurotrophic signaling pathways in the hippocampus. Brain Res. 1720: 146322 (2019) https://doi.org/10.1016/j.brainres.2019.146322
  10. Deogracias R, Espliguero G, Iglesias T, Rodriguez-Pena A. Expression of the neurotrophin receptor trkB is regulated by the cAMP/CREB pathway in neurons. Mol. Cell Neurosci. 26: 470-480 (2004) https://doi.org/10.1016/j.mcn.2004.03.007
  11. Dong Y, Yin S, Jiang C, Luo X, Guo X, Zhao C, et al. Involvement of autophagy induction in penta-1,2,3,4,6-O-galloyl-beta-D-glucose-induced senescence-like growth arrest in human cancer cells. Autophagy. 10: 296-310 (2014) https://doi.org/10.4161/auto.27210
  12. Fujiwara H, Tabuchi M, Yamaguchi T, Iwasaki K, Furukawa K, Sekiguchi K, et al. A traditional medicinal herb Paeonia suffruticosa and its active constituent 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose have potent anti-aggregation effects on Alzheimer's amyloid beta proteins in vitro and in vivo. J. Neurochem. 109: 1648-1657 (2009) https://doi.org/10.1111/j.1471-4159.2009.06069.x
  13. Gold PW. The PPARg system in major depression: pathophysiologic and therapeutic implications. Int. J Mol. Sci. 22: 9248 (2021) https://doi.org/10.3390/ijms22179248
  14. Guo XX, He QZ, Li W, Long DX, Pan XY, Chen C, et al. Brain-derived neurotrophic factor mediated perfluorooctane sulfonate induced-neurotoxicity via epigenetics regulation in SK-N-SH cells. Int. J. Mol. Sci. 18: 893 (2017) https://doi.org/10.3390/ijms18040893
  15. Health insurance review & assessment service. Available from: https://www.hira.or.kr/bbsDummy.do?pgmid=HIRAA020041000100&brdScnBltNo=4&brdBltNo=10146&pageIndex=18. Accessed Sep. 21, 2020.
  16. Jabril E, Gilbert Blaise. The role of acetylcholinesterase inhibitors such as neostigmine and rivastigmine on chronic pain and cognitive function in aging: A review of recent clinical applications. Alzheimers Dement (NY). 5: 175-183 (2019) https://doi.org/10.1016/j.trci.2019.03.004
  17. Kandiah N, Pai MC, Senanarong V, Looi I, Ampil E, Park KW, et al. Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and parkinson's disease dementia. Clin. Interv. Aging. 12: 697-707 (2017) https://doi.org/10.2147/CIA.S129145
  18. Kim YH, Im AR, Park BK, Paek SH, Choi G, Kim YR, et al. Anti-depressant-Like and Neuroprotective Effects of Ethanol Extract from the Root Bark of Hibiscus syriacus L. Biomed. Res. Int. 2018: 7383869 (2018)
  19. Knight R, Khondoker M, Magill N, Stewart R, Landau S. A systematic review and meta-analysis of the effectiveness of acetylcholinesterase inhibitors and memantine in treating the cognitive symptoms of dementia. Dement. Geriatr. Cogn. Disord. 45: 131-151 (2018) https://doi.org/10.1159/000486546
  20. Lee HI, Gwak JY, Chung MJ. Inhibitory effects of Platycodon Grandiflorum, Codonopsis lanceolata, Corn Silk, and Acanthopanax senticosus against Nitric Oxide-Induced cytotoxicity in SK-N-SH Cells. J. Korean Soc. Food Sci. Nutr. 48: 823-832 (2019) https://doi.org/10.3746/jkfn.2019.48.8.823
  21. Lee HJ, Seong YH, Bae KH, Kwon SH, Kwak HM, Nho SK, et al. Beta-secretase (BACE1) inhibitors from Sanguisorbae Radix. Arch. Pharm. Res. 28: 799-803 (2005) https://doi.org/10.1007/BF02977345
  22. Lisman J, Yasuda R, Raghavachari S. Mechanisms of CaMKII action in long-term potentiation. Nat. Rev. Neurosci. 13: 169-182 (2012) https://doi.org/10.1038/nrn3192
  23. Luca CDA, Luisa S, Floriana V. Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. Int. J. Mol. Sci. 21: 7777 (2020) https://doi.org/10.3390/ijms21207777
  24. Mendonca P, Taka E, Bauer D, Cobourne-Duval M, Soliman KF. The attenuating effects of 1,2,3,4,6-penta-O-galloyl-beta-D-glucose on inflammatory cytokines release from activated BV-2 microglial cells. J. Neuroimmunol. 15: 9-15 (2017)
  25. Numakawa T, Odaka H, Adachi N. Action of brain-derived neurotrophin factor in the neurogenesis and neuronal function, and its involvement in the pathophysiology of brain diseases. Int. J. Mol. Sci. 19: 3650 (2018) https://doi.org/10.3390/ijms19113650
  26. Patel SS, Raghuwanshi R, Masood M, Acharya A, Jain SK. Medicinal plants with acetylcholinesterase inhibitory activity. Rev. Neurosci. 29: 491-529 (2018) https://doi.org/10.1515/revneuro-2017-0054
  27. Ren Y, Himmeldirk K, Chen X. Synthesis and structure-activity relationship study of antidiabetic penta-O-galloyl-D-glucopyranose and its analogues. J Med. Chem. 49: 2829-2837 (2006) https://doi.org/10.1021/jm060087k
  28. Statistics Korea. 2020 Statistics on the Aged. Available from: http://kostat.go.kr/portal/eng/pressReleases/1/index.board?bmode=read&bSeq=&aSeq=388599&pageNo=10&rowNum=10&navCount=10&currPg=&searchInfo=&sTarget=title&sTxt=. Accessed Sep. 28, 2020.
  29. Tu Z, Gong W, Zhang Y, Feng Y, Liu Y, Tu C. Inhibition of Rabies virus by 1,2,3,4,6-penta-O-galloyl-beta-d-glucose involves mTOR-dependent autophagy. Viruses 10: 201 (2018) https://doi.org/10.3390/v10040201
  30. Wang Y, Yin F, Guo H, Zhang J, Yan P, Lai J. The Role of Dopamine D1 and D3 Receptors in N-Methyl-D-Aspartate (NMDA)/ GlycineB Site-Regulated Complex Cognitive Behaviors following Repeated Morphine Administration. Int. J. Neuropsychopharmacol. 20: 562-574 (2017) https://doi.org/10.1093/ijnp/pyx010
  31. Whang SG, Park HG. An analysis on prescribing patterns of alzheimer's dementia treatment and choline alfoscerate using HIRA claims data. Kor. J. Clin. Pharm. 29: 1-8 (2019) https://doi.org/10.24304/kjcp.2019.29.1.1