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Biomol Ther (Seoul). 2014 Jul;22(4):275-81. doi: 10.4062/biomolther.2014.068.

Neuroprotective Effect of Chebulagic Acid via Autophagy Induction in SH-SY5Y Cells.

Biomolecules & therapeutics

Hee Ju Kim, Joonki Kim, Ki Sung Kang, Keun Taik Lee, Hyun Ok Yang

Affiliations

  1. Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340 ; Gangneung-Wonju National University, Gangneung 210-702, Republic of Korea.
  2. Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340.
  3. Gangneung-Wonju National University, Gangneung 210-702, Republic of Korea.

PMID: 25143804 PMCID: PMC4131520 DOI: 10.4062/biomolther.2014.068

Abstract

Autophagy is a series of catabolic process mediating the bulk degradation of intracellular proteins and organelles through formation of a double-membrane vesicle, known as an autophagosome, and fusing with lysosome. Autophagy plays an important role of death-survival decisions in neuronal cells, which may influence to several neurodegenerative disorders including Parkinson's disease. Chebulagic acid, the major constituent of Terminalia chebula and Phyllanthus emblica, is a benzopyran tannin compound with various kinds of beneficial effects. This study was performed to investigate the autophagy enhancing effect of chebulagic acid on human neuroblastoma SH-SY5Y cell lines. We determined the effect of chebulagic acid on expression levels of autophago-some marker proteins such as, DOR/TP53INP2, Golgi-associated ATPase Enhancer of 16 kDa (GATE 16) and Light chain 3 II (LC3 II), as well as those of its upstream pathway proteins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Beclin-1. All of those proteins were modulated by chebulagic acid treatment in a way of enhancing the autophagy. Additionally in our study, chebulagic acid also showed a protective effect against 1-methyl-4-phenylpyridinium (MPP(+)) - induced cytotoxicity which mimics the pathological symptom of Parkinson's disease. This effect seems partially mediated by enhanced autophagy which increased the degradation of aggregated or misfolded proteins from cells. This study suggests that chebulagic acid is an attractive candidate as an autophagy-enhancing agent and therefore, it may provide a promising strategy to prevent or cure the diseases caused by accumulation of abnormal proteins including Parkinson's disease.

Keywords: 1-Methyl-4-phenylpyridinium (MPP+); Autophagy; Chebulagic acid; Parkinson’s disease

References

  1. J Cell Sci. 2004 Jun 1;117(Pt 13):2805-12 - PubMed
  2. Histol Histopathol. 2002;17(3):897-908 - PubMed
  3. Autophagy. 2009 Nov;5(8):1155-65 - PubMed
  4. Hum Mol Genet. 2006 Apr 1;15(7):1209-16 - PubMed
  5. Nat Cell Biol. 2007 Feb;9(2):218-24 - PubMed
  6. Ann N Y Acad Sci. 2004 Oct;1025:267-73 - PubMed
  7. Am J Physiol Heart Circ Physiol. 2008 Mar;294(3):H1119-29 - PubMed
  8. J Ethnopharmacol. 2011 Mar 24;134(2):313-22 - PubMed
  9. Neurochem Res. 2011 Nov;36(11):2043-50 - PubMed
  10. Autophagy. 2009 Apr;5(3):383-4 - PubMed
  11. Cardiovasc Res. 2010 Apr 1;86(1):103-12 - PubMed
  12. EMBO Rep. 2010 Jan;11(1):4-5 - PubMed
  13. Neuron. 2003 Sep 11;39(6):889-909 - PubMed
  14. Neuroscience. 2009 Dec 1;164(2):541-51 - PubMed
  15. Neurosignals. 2011;19(3):163-74 - PubMed
  16. Int J Biochem Cell Biol. 2004 Dec;36(12):2503-18 - PubMed
  17. Hum Mol Genet. 2010 Sep 1;19(17):3413-29 - PubMed
  18. Science. 2003 Sep 5;301(5638):1387-91 - PubMed
  19. EMBO Rep. 2010 Jan;11(1):37-44 - PubMed
  20. Neurobiol Dis. 2008 Oct;32(1):16-25 - PubMed
  21. Mol Biol Cell. 2009 Feb;20(3):870-81 - PubMed
  22. Genes Dev. 2004 Aug 15;18(16):1926-45 - PubMed
  23. Autophagy. 2012 May 1;8(5):812-25 - PubMed
  24. Free Radic Biol Med. 2005 Mar 15;38(6):806-16 - PubMed
  25. Brain Res. 2004 Apr 2;1003(1-2):86-97 - PubMed
  26. Evid Based Complement Alternat Med. 2012;2012:125247 - PubMed
  27. Eur J Cancer Prev. 2011 May;20(3):225-39 - PubMed
  28. Nature. 2006 Jun 15;441(7095):885-9 - PubMed
  29. J Cell Biochem. 2011 Sep;112(9):2471-9 - PubMed
  30. Chin Med J (Engl). 2012 Sep;125(17):3120-6 - PubMed
  31. Brain. 2008 Aug;131(Pt 8):1969-78 - PubMed
  32. EMBO J. 2010 Jun 2;29(11):1792-802 - PubMed
  33. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1889-92 - PubMed
  34. J Neural Transm (Vienna). 2003 Aug;110(8):835-45 - PubMed
  35. Endocrinology. 2007 Jul;148(7):3068-76 - PubMed
  36. Neurosci Lett. 2010 Oct 4;482(3):264-8 - PubMed
  37. Neurosci Lett. 2010 Mar 12;472(1):47-52 - PubMed
  38. J Biol Chem. 2005 Jan 21;280(3):2132-40 - PubMed

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