Neuroprotective effects of chloroform and aqueous fractions of noni juice against t-Butyl hydroperoxide-induced oxidative damage in SH-SY5Y cells

  • Jianguo Chen
  • Xue Shi
  • Yang Chen
  • Hanqiao Liang
  • Chi Cheng
  • Qiyang He
Keywords: Noni juice, Neuroprotective, Oxidative stress, Nrf2, Apoptosis


Oxidative stress is more likely to cause damage to neuronal cells and mediates some neurodegenerative disorders. It is well known that natural antioxidants can prevent oxidative stress damage and become a potential therapeutic strategy. Noni juice obtained from the fruit of the tree Morinda citrifolia, as a folk medicine, has been used for over two thousand years. In the current study, the neuroprotective effect and mechanism of noni juice extracts against tert-Butyl hydroperoxide (TBHP)-induced SH-SY5Y cell damage were investigated. The results demonstrated that chloroform fraction (CF) and aqueous fraction (AF) of noni juice protected SH-SY5Y cells against TBHP-induced oxidative stress and the associated apoptosis effectively. CF and AF treatment significantly weakened the TBHP-induced cytotoxicity, reactive oxygen species generation, mitochondrial membrane depolarization, and apoptotic features. CF and AF restored cellular antioxidant enzyme activity; upregulated expression of heme oxygenase-1, catalase, and superoxide dismutase-1; and increased the nuclear accumulation of nuclear factor-erythroid 2 related factor 2 (Nrf2). The antioxidant and neuroprotection potential of CF may account for its high total phenolic and flavonoid content, while AF may be rich in polysaccharides. These results suggest that CF and AF exhibit antioxidant defense through the upregulation of Nrf2 along with endogenous antioxidants and reduce apoptosis via inhibiting the mitochondrial pathway to protect SH-SY5Y cells damaged by TBHP. CF and AF might be developed as agents for neurodegeneration prevention or therapy.


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  1. Friedman J. Why is the nervous system vulnerable to oxidative stress? In: Gadoth N, Gobel HH, eds. Oxidative stress in applied basic research and clinical practice. The Humana Press, New York; 2011, pp. 19–27.

  2. Bhat AH, Dar KB, Anees S, Zargar MA, Masood A, Sofi MA. Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; A mechanistic insight. Biomed Pharmacother. 2015; 74: 101–10.

  3. Jiang T, Sun Q, Chen S. Oxidative stress: a major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson's disease and Alzheimer's disease. Prog Neurobiol. 2016; 147: 1–19.

  4. Chi-Rei W, Mei-Yueh H, Yung-Ta L, Heng-Yin J, Hui Ching. Oxidative stress and neurodegenerative disease. Neurosciences. 2014; 9(9): 19–23.

  5. Zawia NH, Lahiri DK, Cardozo-Pelaez F. Epigenetics, oxidative stress, and Alzheimer disease. Free Radical Biol Med. 2009; 46(9): 1241–9.

  6. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014; 29(13): 1583–90.

  7. Kalonia H, Kumar P, Kumar A. Attenuation of pro-inflammatory cytokines and apoptotic process by verapamil and diltiazem against quinolinic acid induced Huntington’s like alteration in rats. Brain Res. 2011; 1372: 115–26.

  8. Kalonia H, Kumar P, Kumar A. Licofelone attenuates quinolinic acid induced Huntington’s like symptoms: possible behavioural, biochemical and cellular alterations. Prog Neuropsycho pharmacol Biol Psychiatry.2011; 35(2): 607–15.

  9. Abushouk AI, Negida A, Ahmed H, Abdel-Daim MM. Neuroprotective mechanisms of plant extracts against MPTP induced neurotoxicity: future applications in Parkinson’s disease. Biomed Pharmacother. 2017; 85: 635–45.

  10. Peng S, Hou Y, Yao J, Fang J. Activation of Nrf2-driven antioxidant enzymes by cardamonin confers neuroprotection of PC12 cells against oxidative damage. Food Funct.2017; 8(3): 997–1007.

  11. Je JY, Lee DB. Nelumbo nucifera leaves protect hydrogen peroxide-induced hepatic damage via antioxidant enzymes and HO-1/Nrf2 activation. Food Funct. 2015; 6(6): 1911–18.

  12. Zhang X, Wang L, Wang R, Luo X, Li Y, Chen Z. Protective effects of rice dreg protein hydrolysates against hydrogen peroxide-inducedoxidative stress in HepG-2 cells. Food Funct. 2016; 7(3): 1429–37.

  13. Hu MX, Zhang HC, Wang Y, Liu SM, Liu L. Two new glycosides from the fruits of Morinda citrifolia. Molecules. 2012; 17(11): 12651–6.

  14. Deng S, West BJ, Palu ‘K, Jensen CJ. Determination and comparative analysis of major iridoids in different parts and cultivationsources of Morinda citrifolia. Phytochem Anal. 2011; 22(1): 26–30.

  15. Bittová M, Hladůkova D, Roblová V, Krácmar S, Kubán P, Kubán V. Analysis of organic acids, deacetyl asperulosidic acid and polyphenolic compounds as a potential tool for characterization of noni (Morinda citrifolia) products. Nat Prod Commun. 2015; 10(11): 1817–20.

  16. Z. Mohd Zin, A. Abdul Hamid, A. Osman, N. Saari & A. Misran. Isolation and identification of anti oxidative compound from fruit of noni. Int J Food Properties. 2009; 10(2): 363–73.

  17. Lin YL, Chou CH, Yang DJ, Chen JW, Tzang BS, Chen YC. Hypolipidemic and antioxidative effects of Noni (Morinda citrifolia L.) Juice on high-fat cholesterol-Dietary hamsters. Plant Foods Hum Nutr. 2012; 67(3): 294–302.

  18. Basar S, Uhlenhut K, Högger P, Schöne F, Westendorf J. Analgesic and anti-inflammatory activity of Morinda citrifolia L. (Noni) fruit. Phytotherapy Res. 2010; 24(1): 38–42.

  19. Nualsanit T, Rojanapanthu P, Gritsanapan W, Lee SH, Lawson D, Baek SJ. Damnacanthal, a noni component, exhibits antitumorigenic activity in human colorectal cancer cells. J Nutr Biochem. 2012; 23(8): 915–23.

  20. Harada S, Hamabe W, Kamiya K, Satake T, Yamamoto J, Tokuyama S. Preventive effect of Morinda citrifolia fruit juice on neuronal damage induced by focal ischemia. Biol Pharm Bull. 2009; 32(3): 405–9.

  21. Harada S, Fujita-Hamabe W, Kamiya K, Mizushina Y, Satake T, Tokuyama S. Morindacitrifolia fruit juice prevents ischemic neuronal damage through suppression of the development of post-ischemic glucose intolerance. J Nat Med. 2010; 64(4): 468–73.

  22. Dillon GP, Gaffney MA, Curran CM, Moran CA. Dietary safety of a dual-enzyme preparation for animal feed: acute and subchronic oral toxicity and genotoxicity studies. Regul Toxicol Pharmacol. 2017; 88: 106–17.

  23. Chi-Rei W, Mei-Yueh H, Yung-Ta L, Heng-Yin J, Hui Ching. Antioxidant properties of Cortex Fraxini and its simple coumarins. Food Chem.2007; 104: 1464–71.

  24. Li S, Shah NP. Characterization, antioxidative and bifidogenic effects of polysaccharides from Pleurotus eryngiiafter heat treatments. Food Chem. 2016; 197(Pt A): 240–9.

  25. Ju HY, Chen SC, Wu KJ, Kuo HC, Hseu YC, Ching H, et al. Antioxidant phenolic profile from ethyl acetate fraction of Fructus Ligustri Lucidi with protection against hydrogen peroxide-induced oxidative damage in SH-SY5Y cells. Food Chem Toxicol. 2012; 50(3–4): 492–502.

  26. Ou X, Chen Y, Cheng X, Zhang X, He Q. Potentiation of resveratrol-induced apoptosis by matrine in human hepatoma HepG2 cells. Oncol Rep. 2014; 32(6): 2803–9.

  27. Chen J, Chen Y, He Q. Action of bleomycin is affected by bleomycin hydrolase but not by caveolin-1. Int J Oncol. 2012; 41(6): 2245–52.

  28. Chen Y, Xu R, Chen J, Li X, He Q. Cleavage of bleomycin hydrolase by caspase-3 during apoptosis. Oncol Rep. 2013; 30(2): 939–44.

  29. Wu CR, Lin WH, Hseu YC, Lien JC, Lin YT, Kuo TP, et al. Evaluation of the antioxidant activity of five endemic Ligustrum species leavesfrom Taiwan flora in vitro. Food Chem. 2011; 127: 564–71.

  30. Zhu F, Cai YZ, Sun M, Ke J, Lu D, Corke H. Comparison of major phenolic constituents and in vitro antioxidant activity of diverse Kudingcha genotypes from Ilex kudingcha, Ilex cornuta, and Ligustrum robustum. J Agric Food Chem. 2009; 57(14): 6082–9.

  31. Hernández I, Alegre L, Van Breusegem F, Munné-Bosch S. How relevant are flavonoids as antioxidants in plants? Trends Plant Sci. 2009; 14(3): 125–32.

  32. Wang J, Hu S, Nie S. Reviews on mechanisms of in vitro antioxidant activity of polysaccharides. Oxid Med Cell Longev. 2016; 13. doi: 10.1155.

  33. Choi BS, Sapkota K, Kim S, Lee HJ, Choi HS, Kim SJ. Antioxidant activity and protective effects of Tripterygium regelii extract on hydrogenperoxide-induced injury in human dopaminergic cells, SH-SY5Y. Neurochem Res. 2010; 35: 1269–80.

  34. Lee DS, Keo S, Cheng SK, Oh H, Kim YC. Protective effects of Cambodian medicinal plants on tertbutyl hydroperoxideinduced hepatotoxicity via Nrf2mediated heme oxygenase1. Mol Med Rep. 2017; 15(1): 451–9.

  35. Ramyaa P, Padma VV. Ochratoxin-induced toxicity, oxidative stress and apoptosis ameliorated by quercetin--modulation by Nrf2. Food Chem Toxicol. 2013; 62: 205–16.

  36. Ramyaa P, Krishnaswamy R, Padma VV. Quercetin modulates OTA-induced oxidative stress and redox signalling in HepG2 cells-up regulation of Nrf2 expression and down regulation of NF-κB and COX-2. Biochim Biophys Acta. 2014; 1840(1): 681–92.

  37. Kumar KH, Khanum F. Hydroalcoholic extract of Cyperus rotundus Ameliorates H2O2-Induced Human Neuronal Cell Damage via its anti-oxidative and anti-apoptotic Machinery. Cell Mol Neurobiol. 2013; 33(1): 5–17.

  38. Nikam S, Nikam P, Ahaley SK, Sontakke AV. Oxidative stress in parkinson’s disease. Indian J Clin Biochem. 2009; 24: 98–101.

  39. de Vries HE, Witte M, Hondius D, Rozemuller AJ, Drukarch B, Hoozemans J. Nrf2-induced antioxidant protection: a promising target to counteract ROS-mediated damage in neurodegenerative disease? Free Radic Biol Med. 2008; 45(10): 1375–83.

  40. Chen PC, Vargas MR, Pani AK, Smeyne RJ, Johnson DA, Kan YW. Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: critical role for the astrocyte. Proc Natl Acad Sci USA. 2009; 106(8): 2933–8.

  41. Rojo AI, Innamorato NG, Martín-Moreno AM, De Ceballos ML, Yamamoto M, Cuadrado A. Nrf2 regulates microglial dynamics and neuro inflammation in experimental Parkinson's disease. Glia. 2010; 58(5): 588–98.

  42. Hara H, Ohta M, Adachi T. Apomorphine protects against 6-hydroxydopamine-induced neuronal cell death through activation of the Nrf2-ARE pathway. J Neurosci Res. 2006; 84(4): 860–6.

  43. Lin YC, Huang YC, Chen SC, Liaw CC, Kuo SC, Huang LJ. Neuroprotective effects of ugonin K on hydrogen peroxide-induced cell death in human neuroblastoma SH-SY5Y cells. Neurochem Res. 2009; 34: 923–30.

  44. Lee CH, Hwang DS, Kim HG, Oh H, Park H, Cho JH, et al. Protective effect of Cyperi rhizoma against 6-hydroxydopamine-inducedneuronal damage. J Med Food. 2010; 13: 564–71.

  45. Doi K, Uetsuka K. Mechanisms of mycotoxin-induced neurotoxicity through oxidative stress-associated pathways. Int J Mol Sci. 2011; 12(8): 5213–37.

  46. Cai L, Wang LF, Pan JP, et al. Neuroprotective effects of Methyl3,4-Dihydroxybenzoate against TBHP-Induced oxidative damage in SH-SY5Y Cells. Molecules. Molecules. 2016, 21(8):1–14.

  47. Hassa, PO, Hottiger, MO. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases. Front Biosci. 2008; 13: 3046–82.

How to Cite
Chen J., Shi X., Chen Y., Liang H., Cheng C., & He Q. (2018). Neuroprotective effects of chloroform and aqueous fractions of noni juice against t-Butyl hydroperoxide-induced oxidative damage in SH-SY5Y cells. Food & Nutrition Research, 62.
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