Neuroprotective Effect of Durio zibithinus against Beta Amyloid

Main Article Content

Kusawadee Plekratoke
Pornthip Waiwut
Natcha P Suchaichit
Nuntavan Bunyapraphatsara
Prasert Reubroycharoen
Chantana Boonyarat


In searching for a promising candidate for treatment of Alzheimer’s disease (AD), the effects of ethanol extract (CE) and defatted ethanol extract (dCE) of Durio zibithinus cultivar “Mon Thong” on pathological cascade of AD were investigated by in vitro and cell culture models. The results exhibited that both of CE and dCE extracts could inhibit acetylcholinesterase function in bioautography assay. For thioflavin T assay which studies an effect on beta-amyloid (Aβ) aggregation indicated that both CE and dCE at the concentration of 10 mg/mL were able to inhibit Aβ aggregation with inhibitory percentage values of 44.96±3.50 and 36.91±5.50, respectively. From the neuroprotection study in cell culture revealed that both CE and dCE could reduce human neuroblastoma cell (SH-SY5Y) death induced by Aβ. Moreover, the result from Western blotting analysis indicated that CE inhibited Aβ- induced cell death via DR5 inhibition, resulting in inhibiting of cleave-caspase 8, cleave-caspase 3 activation and changing in the phosphorylation level of Akt (protein kinase B). The overall results indicated that the Durio zibithinus extract possesses multimode of action involved with AD pathology cascade including anti-Aβ aggregation, acetylcholinesterase inhibition, and neuroprotection against β-amyloid. Thus, the Durio zibithinus cultivar “Mon Thong” might be a potential candidate for further developing as a functional food or a drug for Alzheimer’s disease.

Article Details

Research Articles
Author Biography

Chantana Boonyarat, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002 Thailand

Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002 Thailand


1. Isacson O, Seo H, Lin L, Albeck D, Granholm AC. Alzheimer’s disease and Down’s syndrome: roles of APP, trophic factors and ACh. Trends Neurosci. 2002 Feb;25(2):79-84.
2. Gómez-Isla T, Hollister R, West H, Mui S, Growdon JH, Petersen RC, Parisi JE, Hyman BT. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann Neurol. 1997 Jan;41(1):17-24.
3. Deutsch JA. The cholinergic synapse and the site of memory. Science. 1971 Nov 19;174(4011):788-94.
4. Perry E, Walker M, Grace J, Perry R. Acetylcholine in mind: a neurotransmitter correlate of consciousness. Trends Neurosci. 1999 Jun;22(6):273-80.
5. Terry AV, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003 Sep;306(3):821-7.
6. Bloem B, Poorthuis RB, Mansvelder HD. Cholinergic modulation of the medial prefrontal cortex: the role of nicotinic receptors in attention and regulation of neuronal activity. Front Neural Circuits. 2014 Mar 11;8:17.
7. Estrada L, Soto C. Disrupting beta-amyloid aggregation for Alzheimer disease treatment. Curr Top Med Chem. 2007;7(1):115-26.
8. Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide. Nat Rev Mol Cell Biol. 2007 Feb;8(2): 101-12.
9. Skovronsky DM, Doms RW, Lee VM-Y. Detection of a novel intraneuronal pool of insoluble amyloid b protein that accumulates with time in culture. J Cell Biol. 1998 May 18;141(4):1031-9.
10. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2002 Jul 19;297(5580):353-6.
11. Laursen B, Mørk A, Plath N, Kristiansen U, Bastlund JF. Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice. Behav Brain Res. 2013 Mar 1;240:146-52.
12. Bartolini M, Bertucci C, Cavrini V, Andrisano V. β-Amyloid aggregation induced by human acetylcholinesterase: inhibition studies. Biochem Pharmacol. 2003 Feb 1;65(3):407-16.
13. Muñoz FJ, Inestrosa NC. Neurotoxicity of acetylcholinesterase amyloid beta-peptide aggregates is dependent on the type of Abeta peptide and the AChE concentration present in the complexes. FEBS Lett. 1999 May 7;450(3):205-9.
14. Inestrosa NC, Dinamarca MC, Alvarez A. Amyloid-cholinesterase interactions. Implications for Alzheimer's disease. FEBS J. 2008 Feb;275(4):625-32.
15. Yan Z, Feng J. Alzheimers disease: interactions between cholinergic functions and β- amyloid. Curr Alzheimer Res. 2004 Nov;1(4):241-8.
16. Muhtadi M, Primarianti AU, Sujono TA. Antidiabetic activity of durian (Durio zibethinus Murr.) and rambutan (Nephelium lappaceum L.) fruit peels in alloxan diabetic rats. Procedia Food Sci 2015;3:255-61.
17. Leontowicz H, Maria L, Ratiporn H, Sumitra P, Zenon J, Jerzy D, et al. Durian (Durio zibethinus Murr.) cultivars as nutritional supplementation to rat’s diets. Food Chem Toxicol. 2008 Feb;46(2):581-9.
18. Haruenkit R, Sumitra P, Suchada V, Jacek N, Magda S, Yong-Seo P, et al. Comparison of bioactive compounds, antioxidant and antiproliferative activities of Mon Thong durian during ripening. Food Chem. 2010;118(3):540-7.
19. Duarte J, Vizcaino FP, Utrilla P, Jimenez J, Tamargo J, Zarzuelo A. Vasodilatory effects of flavonoids in rat aortic smooth muscle. Structure–activity relationships. Gen Pharmacol. 1993 Jul;24(4):857-62.
20. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009 Nov-Dec;2(5):270-8.
21. Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev. 2003 Jul;23(4):519-34.
22. Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin- induced diabetic rats. Comp Biochem Physiol C Toxicol Pharmacol. 2003 Jul; 135C(3):357-64.
23. Marston A, Kissling J, Hostettmann K. A rapid TLC bioautographic method for the detection of acetylcholinesterase and butyrylcholinesterase inhibitors in plants. Phytochem Anal. 2002 Jan-Feb;13(1):51-4.
24. Levine H. Thioflavine T interaction with synthetic Alzheimer's disease β-amyloid peptides: detection of amyloid aggregation in solution. Protein Sci. 1993 Mar; 2(3):404-10.
25. Park HR, Lee H, Park H, Jeon JW, Cho WK, Ma JY. Neuroprotective effects of Liriope platyphylla extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. BMC Complement Altern Med. 2015 Jun 9;15:171
26. Waiwut P, Shin MS, Inujima A, et al. Gomisin N enhances TNF-α-induced apoptosis via inhibition of the NF-κB and EGFR survival pathways. Mol Cell Biochem. 2011 Apr;350(1-2):169-75 .
27. Toledo F, Arancibia-Avila P, Park YS, Jung ST, Kang SG, Heo BG, et al. Screening of the antioxidant and nutritional properties, phenolic contents and proteins of five durian cultivars. Int J Food Sci Nutr. 2008 Aug;59(5):415-27.
28. Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J. Cholinesterase inhibitors used in the treatment of Alzheimer’s disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 2004;21(7):453-78.
29. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002; 297: 353-356.
30. Blennow K, De Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006 Jul 29;368(9533):387-403.
31. Wogulis M, Wright S, Cunningham D, Chilcote T, Powell K, Rydel RE. Nucleation-dependent polymerization is an essential component of amyloid-mediated neuronal cell death. J Neurosci. 2005 Feb 2;25(5):1071-80.
32. Deshpande A, Mina E, Glabe C, Busciglio J. Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons. J Neurosci. 2006 May 31;26(22):6011-8.
33. Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, et al. A specific amyloid-beta protein assembly in the brain impairs memory. Nature. 2006 Mar 16;440(7082):352-7.
34. Yatin SM, Varadarajan S, Link CD, Butterfield DA. In vitro and in vivo oxidative stress associated with Alzheimer’s amyloid beta-peptide (1-42). Neurobiol Aging. 1999 May-Jun;20(3):325-30.
35. Cardoso SM, Santos S, Swerdlow RH, Oliveira CR. Functional mitochondria are required for amyloid beta-mediated neurotoxicity. FASEB J. 2001 Jun;15(8): 1439-41.
36. Yun SH, Gamkrelidze G, Stine WB, Sullivan PM, Pasternak JF, Ladu MJ, et al. Amyloid-beta1-42 reduces neuronal excitability in mouse dentate gyrus. Neurosci Lett. 2006 Jul 31;403(1-2):162-5.
37. Joseph JA, Shukitt-Hale B, Casadesus G. Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr. 2005 Jan;81(1 Suppl):313S-316S.
38. Pedraza-Chaverri J, Cardenas-Rodriguez N, Orozco-Ibarra M, Perez-Rojas JM. Medicinal properties of mangosteen (Garcinia mangostana). Food Chem Toxicol. 2008 Oct;46(10):3227-39.
39. Chin YW, Jung HA, Chai H, Keller WJ, Kinghorn AD. Xanthones with quinone reductase-inducing activity from the fruits of Garcinia mangostana (mangosteen). Phytochemistry. 2008 Feb;69(3):754-8.
40. Chingsuwanrote P, Muangnoi C, Parengam K, Tuntipopipat S. Antioxidant and anti-inflammatory activities of durian and rambutan pulp extract. Int Food Res J. 2016;23(3):939-47.
41. Onoue S, Endo K, Ohshima K, Yajima T, Kashimoto K. The neuropeptide PACAP attenuates beta-amyloid (1-42)-induced toxicity in PC12 cells. Peptides. 2002 Aug;23(8):1471-8.
42. Gervais FG, Xu D, Robertson GS, Vaillancourt JP, Zhu Y, Huang J, et al. Involvement of caspases in proteolytic cleavage of Alzheimer’s amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell. 1999 Apr 30;97(3):395-406.
43. Vassar R. Caspase-3 cleavage of GGA3 stabilizes BACE: implications for Alzheimer’s disease. Neuron. 2007 Jun 7;54(5):671-3.
44. Gamblin TC, Chen F, Zambrano A, Abraha A, Lagalwar S, Guillozet AL, et al. Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer’s disease. Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):10032-7.