Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

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

  • Kim, Hee Ju (Natural Medicine Center, Korea Institute of Science and Technology) ;
  • Kim, Joonki (Natural Medicine Center, Korea Institute of Science and Technology) ;
  • Kang, Ki Sung (Natural Medicine Center, Korea Institute of Science and Technology) ;
  • Lee, Keun Taik (Gangneung-Wonju National University) ;
  • Yang, Hyun Ok (Natural Medicine Center, Korea Institute of Science and Technology)
  • Received : 2014.06.05
  • Accepted : 2014.07.04
  • Published : 2014.07.31
Download PDF
⟨ Previous Next ⟩

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 autophagosome 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

References

  1. Bae, N. Y., Ahn, T. K., Chung, S. K., Oh, M. S., Ko, H. S., Oh, H. G., Park, G. H. and Yang, H. O. (2011) The neuroprotective effect of modified Yeoldahanso-tang via autophagy enhancement in models of Parkinson's disease. J. Ethnopharmacol. 134, 313-322. https://doi.org/10.1016/j.jep.2010.12.016
  2. Baliga, M. S. and Dsouza, J. J. (2011) Amla(Emblica offi cinalis Gaertn), a wonder berry in the treatment and prevention of cancer. Eur. J. Cancer Prev. 20, 225-239. https://doi.org/10.1097/CEJ.0b013e32834473f4
  3. Bao, X. X., Xie, B. S., Li, Q., Li, X. P., Wei, L. H. and Wang, J. L. (2012) Nifedipine induced autophagy through Beclin1 and mTOR pathway in endometrial carcinoma cells. Chin. Med. J. 125, 3120-3126
  4. Bollimuntha, S., Singh, B. B. and Shavali, S. (2005) TRPC1-mediated inhibition of 1-methyl-4-phenylpyridinium ion neurotoxicity in human SH-SY5Y neuroblastoma cells. J. Biol. Chem. 280, 2132-2140. https://doi.org/10.1074/jbc.M407384200
  5. Chang, C. L. and Lin, C. S. (2012) Phytochemical composition, antioxidant activity, and neuroprotective effect of Terminalia chebula Retzius extracts. Evid. Based Complement. Alternat. Med. 2012, 125247.
  6. Chen, X. C., Fang, F., Zhu, Y. G., Chen, L. M., Zhou, Y. C. and Chen, Y. (2003) Protective effect of ginsenoside Rg1 on $MPP^+$-induced apoptosis in SH-SY5Y cells. J. Neural Transm. 110, 835-845. https://doi.org/10.1007/s00702-003-0005-y
  7. Chen, Z., Lu, T., Yue, X., Wei, N., Jiang, Y., Chen, M., Ni, G., Liu, X. and Xu, G. (2010) Neuroprotective effect of ginsenoside Rb1 on glutamate-induced neurotoicity : With emphasis on autophagy. Neurosci. Lett. 482, 264-268. https://doi.org/10.1016/j.neulet.2010.07.052
  8. Choi, J. Y., Jang, E. H., Park, C. S. and Kang, J. H. (2005) Enhanced susceptibility to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine neurotoxicity in high-fat diet induced obesity. Free Radic. Biol. Med. 38, 806-816. https://doi.org/10.1016/j.freeradbiomed.2004.12.008
  9. Dadakhujaev, S., Noh, H. S., Jung, E. J., Cha, J. Y., Baek, S. M., Ha, J. H. and Kim, D. R. (2010) Autophagy protects the rotenone-induced cell death in alpha-synuclein overexpressing SH-SY5Y cells. Neurosci. Lett. 472, 47-52 . https://doi.org/10.1016/j.neulet.2010.01.053
  10. Dauer, W. and Przedborski, S. (2003) Parkinson's disease: mechanisms and models. Neuron 39, 889-909 . https://doi.org/10.1016/S0896-6273(03)00568-3
  11. Gurusamy, N., Lekli, I., Mukherjee, S., Ray, D., Ahsan, K., Gherghiceanu, M., Popescu, L. M. and Das, D. K. (2010) Cardioprotection by resveratrol: a novel mechanism via autophagy involving the mTORC2 pathway. Cardiovasc. Res. 86, 103-112. https://doi.org/10.1093/cvr/cvp384
  12. Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Ichiro, S., Okano, H. and Mizushima, N. (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885-889. https://doi.org/10.1038/nature04724
  13. Han, J., Pan, X. Y., Xu, Y., Xiao, Y., An, Y., Tie, L., Pan, Y. and Li, X. J. (2012) Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage. Autophagy 8, 812-825. https://doi.org/10.4161/auto.19471
  14. Hay, N. and Sonenberg, N. (2004) Upstream and downstream of mTOR. Genes Dev. 18, 1926-1945. https://doi.org/10.1101/gad.1212704
  15. Kabeya, Y., Mizushima, N., Yamamoto, A., Satsuki, O. O., Ohsumi, Y. and Yoshimori, T. (2004) LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J. Cell Sci. 117, 2805-2812. https://doi.org/10.1242/jcs.01131
  16. Ko, H. S., Kim, Y. J., Amor, E. C., Lee, J. W., Kim, H. C., Kim, H. J. and Yang, H. O. (2011) Induction of autophagy by dimethyl cardamonin is associated with proliferative arrest in human colorectal carcinoma HCT116 and LOVO cells. J. Cell. Biochem. 112, 2471-2479. https://doi.org/10.1002/jcb.23171
  17. Larsen, K. E. and Sulzer, D. (2002) Autophagy in neurons: a review. Histol. Histopathol. 17, 897-908.
  18. Liang, J., Shao, S. H., Xu, Z. X., Hennessy, B., Ding, Z., Larrea, M., Kondo, S., Dumont, D. J., Gutterman, J. U., Walker, C. L., Slingerland, J. M. and Mills, G. B. (2007) The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat. Cell. Biol. 9, 218-224. https://doi.org/10.1038/ncb1537
  19. Liu, D., Si, H., Reynolds, K. A., Zhen, W., Jia, Z. and Dillon, J. S. (2007) Dehydroepiandrosterone protects vascular endothelial cells against apoptosis through a Galphai protein-dependent activation of phosphatidylinositol 3-kinase/Akt and regulation of antiapoptotic Bcl-2 expression. Endocrinology 148, 3068-3076. https://doi.org/10.1210/en.2006-1378
  20. Mathiasen, J. R., McKenna, B. A., Saporito, M. S., Ghadge, G. D., Roos, R. P., Holskin, B. P., Wu, Z. L., Trusko, S. P., Connors, T. C., Maroney, A. C., Thomas, B. A., Thomas, J. C. and Bozyczko- Coyne, D. (2004) Inhibition of mixed lineage kinase 3 attenuates $MPP^+$-induced neurotoxicity in SH-SY5Y cells. Brain Res. 1003, 86-97. https://doi.org/10.1016/j.brainres.2003.11.073
  21. Mauvezin, C., Orpinell, M., Francis, V. A., Mansilla, F., Duran, J., Ribas, V., Palacin, M., Boya, P., Teleman, A. A. and Zorzano, A. (2010) The nuclear cofactor DOR regulates autophagy in mammalian and Drosophila cells. EMBO Rep. 11, 37-44. https://doi.org/10.1038/embor.2009.242
  22. Melendez, A., Talloczy, Z., Seaman, M., Eskelinen, E. L., Hall, D. H. and Levine, B. (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301, 1387-1391. https://doi.org/10.1126/science.1087782
  23. Nowak, J., Archange, C., Joel, T. L., Pontarotti, P., Pe'busque, M., Vaccaro, M. I., Velasco, G., Dagorn, J. C. and Iovanna, J. L. (2009) The TP53INP2 protein is required for autophagy in mammalian cells. Mol. Biol. Cell 20, 870-881.
  24. Nowak, J. and Iovanna, J. L. (2009) TP53INP2 is the new guest at the table of self-eating. Autophagy 5, 383-384. https://doi.org/10.4161/auto.5.3.7698
  25. Pan, T., Kondo, S., Le, W. and Jankovic, J. (2008a) The role of autophagy- lysosome pathway in neurodegeneration associated with Parkinson's disease. Brain 131, 1969-1978. https://doi.org/10.1093/brain/awm318
  26. Pan, T., Kondo, S., Zhu, W., Xie, W., Jankovic, J. and Le, W. (2008b) Neuroprotection of rapamycin in lactacystin-induced neurodegeneration via autophagy enhancement. Neurobiol. Dis. 32, 16-25. https://doi.org/10.1016/j.nbd.2008.06.003
  27. Pan, T., Rawal, P., Wu, Y., Xie, W., Jankovic, J. and Le, W. (2009) Rapamycin protects against rotenone-induced apoptosis through autophagy induction. Neuroscience 164, 541-551. https://doi.org/10.1016/j.neuroscience.2009.08.014
  28. Park, J. H., Joo, H. S., Yoo, K. Y., Shin, B. N., Kim, I. H., Lee, C. H., Choi, J. H., Byun, K., Lee, B., Lim, S. S., Kim, M. J. and Won, M. H. (2011) Extract from Terminalia chebula seeds protect against experimental ischemic neuronal damage via maintaining SODs and BDNF levels. Neurochem. Res. 36, 2043-2050. https://doi.org/10.1007/s11064-011-0528-9
  29. Patschan, S., Chen, J. and Polotskaia, A. (2008) Lipid mediators of autophagy in stressinduced premature senescence of endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 294, 1119-1129. https://doi.org/10.1152/ajpheart.00713.2007
  30. Per, O. S. and Paul, B. G. (1982) 3-methyladenine: specifi c inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Nati. Acad. Sci. U.S.A. 79, 1889-1892. https://doi.org/10.1073/pnas.79.6.1889
  31. Ravikumar, B., Berger, Z., Vacher, C., O'Kane, C. J. and Rubinsztein, D. C. (2006) Rapamycin pre-treatment protects against apoptosis. Hum. Mol. Genet. 15, 1209-1216. https://doi.org/10.1093/hmg/ddl036
  32. Shin, H. Y., Chu, S. H., Lee, H. K. and Lee, J. W. (2011) mTOR inhibitor as a potential drug of age-related disease. Korean. J. Clin. Geri. 12, 149-159.
  33. Spowart, J. and Lum, J. J. (2010) Opening a new DOR to autophagy. EMBO. Rep. 11, 4-5. https://doi.org/10.1038/embor.2009.265
  34. Tanida, I., Ueno, T. and Kominami, E. (2004) LC3 conjugation system in mammalian autophagy. Int. J. Biochem. Cell Biol. 36, 2503-2518. https://doi.org/10.1016/j.biocel.2004.05.009
  35. Underwood, B. R., Imarisio, S., Fleming, A., Rose, C., Krishna, G., Heard, P., Quick, M., Korolchuk, V. I., Renna, M., Sarkar, S., Garcia-Arencibia, M., O'Kane, C. J., Murphy, M. P. and Rubinsztein, D. C. (2010) Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease. Hum. Mol. Genet. 19, 3413-3429. https://doi.org/10.1093/hmg/ddq253
  36. Virmani, A., Gaetani, F., Binienda, Z., Xu, A., Duhart, H. and Ali, S. F. (2004) Role of mitochondrial dysfunction in neurotoxicity of $MPP^+$: partial protection of PC12 cells by acetyl-L-carnitine. Ann. N. Y. Acad. Sci. 1025, 267-273. https://doi.org/10.1196/annals.1316.033
  37. Weidberg, H., Shvets, E., Shpilka, T., Shimron, F., Shinder, V. and Elazar, Z. (2010) LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J. 29, 1792-1802. https://doi.org/10.1038/emboj.2010.74
  38. Williams, T., Forsberg, L. J., Viollet, B. and Brenman, J. E. (2009) Basal autophagy induction without AMP-activated protein kinase under low glucose conditions. Autophagy 5, 1155-1165. https://doi.org/10.4161/auto.5.8.10090
  39. Wu, Y., Li, X., Zhu, J. X., Xie, W., Le, W., Fan, Z., Jankovic, J. and Pan, T. (2011) Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson's disease. Neurosignals 19, 163-174. https://doi.org/10.1159/000328516

Cited by

  1. Rapamycin inhibits oxidative/nitrosative stress and enhances angiogenesis in high glucose-treated human umbilical vein endothelial cells: Role of autophagy vol.93, 2017, https://doi.org/10.1016/j.biopha.2017.07.044
  2. Insulin involved Akt/ERK and Bcl-2/Bax pathways against oxidative damages in C6 glial cells vol.36, pp.1, 2016, https://doi.org/10.3109/10799893.2014.970276
  3. Terminalia chebula attenuates quinolinate-induced oxidative PC12 and OLN-93 cell death vol.14, 2017, https://doi.org/10.1016/j.msard.2017.03.012
  4. Protective effects of a herbal extract combination of Bupleurum falcatum , Paeonia suffruticosa , and Angelica dahurica against MPTP-induced neurotoxicity via regulation of nuclear receptor-related 1 protein vol.340, 2017, https://doi.org/10.1016/j.neuroscience.2016.10.029
  5. Anticancer Properties ofPhyllanthus emblica(Indian Gooseberry) vol.2015, 2015, https://doi.org/10.1155/2015/950890
  6. Terminalia Chebula provides protection against dual modes of necroptotic and apoptotic cell death upon death receptor ligation vol.6, pp.1, 2016, https://doi.org/10.1038/srep25094
  7. Recent advances in autophagy-based neuroprotection vol.15, pp.2, 2015, https://doi.org/10.1586/14737175.2015.1002087
  8. Effects of triphala and guggul aqueous extracts on inhibition of protein fibrillation and dissolution of preformed fibrils vol.7, pp.33, 2017, https://doi.org/10.1039/C6RA28440J
  9. mTOR Signaling in Parkinson’s Disease vol.19, pp.1, 2017, https://doi.org/10.1007/s12017-016-8417-7
  10. A Review on Potential Mechanisms ofTerminalia chebulain Alzheimer’s Disease vol.2016, 2016, https://doi.org/10.1155/2016/8964849
  11. Critical role of protein L-isoaspartyl methyltransferase in basic fibroblast growth factor-mediated neuronal cell differentiation vol.49, pp.8, 2016, https://doi.org/10.5483/BMBRep.2016.49.8.020
  12. Autophagy Regulates Colistin-Induced Apoptosis in PC-12 Cells vol.59, pp.4, 2015, https://doi.org/10.1128/AAC.04092-14
  13. Nootropic and Anti-Alzheimer’s Actions of Medicinal Plants: Molecular Insight into Therapeutic Potential to Alleviate Alzheimer’s Neuropathology pp.1559-1182, 2019, https://doi.org/10.1007/s12035-018-1420-2
  14. modulation of neurotransmitters pp.00223573, 2018, https://doi.org/10.1111/jphp.13007
  15. Ghrelin protects adult rat hippocampal neural stem cells from excessive autophagy during oxygen-glucose deprivation vol.65, pp.1, 2014, https://doi.org/10.1507/endocrj.ej17-0281
  16. Protective effects of extracellular polymeric substances from Aphanizomenon flos-aquae on neurotoxicity induced by local anesthetics vol.16, pp.4, 2014, https://doi.org/10.3892/etm.2018.6540
  17. Chinese Herbal Complex ‘Bu Shen Jie Du Fang' (BSJDF) Modulated Autophagy in an MPP + -Induced Cell Model of Parkinson's Disease vol.2019, pp.None, 2014, https://doi.org/10.1155/2019/8920813
  18. A liquid chromatography–tandem mass spectrometry method for preclinical pharmacokinetics and tissue distribution of hydrolyzable tannins chebulinic acid and chebulagic acid in rats vol.33, pp.3, 2019, https://doi.org/10.1002/bmc.4425
  19. Effects of the Nintendo Wii training on balance rehabilitation and quality of life of patients with Parkinson’s disease: A systematic review and meta-analysis vol.44, pp.4, 2014, https://doi.org/10.3233/nre-192700
  20. Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs vol.9, pp.7, 2014, https://doi.org/10.3390/biom9070269
  21. Targeting apoptosis and autophagy following spinal cord injury: Therapeutic approaches to polyphenols and candidate phytochemicals vol.160, pp.None, 2014, https://doi.org/10.1016/j.phrs.2020.105069
  22. Fruits of Terminalia chebula Retz.: A review on traditional uses, bioactive chemical constituents and pharmacological activities vol.34, pp.10, 2014, https://doi.org/10.1002/ptr.6702
  23. Chebulinic acid inhibits MDA‐MB‐231 breast cancer metastasis and promotes cell death through down regulation of SOD1 and induction of autophagy vol.44, pp.12, 2020, https://doi.org/10.1002/cbin.11463
  24. Ferroptosis-Inhibitory Difference between Chebulagic Acid and Chebulinic Acid Indicates Beneficial Role of HHDP vol.26, pp.14, 2014, https://doi.org/10.3390/molecules26144300