Neurochemical Research

, Volume 35, Issue 3, pp 357–365 | Cite as

Effect of Purple Sweet Potato Anthocyanins on β-Amyloid-Mediated PC-12 Cells Death by Inhibition of Oxidative Stress

  • Junli Ye
  • Xiangjun Meng
  • Chunling Yan
  • Chunbo Wang
Original Paper

Abstract

Amyloid-beta peptide (Aβ) is known to induce the redox imbalance, mitochondrial dysfunction and caspase activation, resulting in neuronal cell death. Treatment with antioxidants provided a new therapeutic strategy for Alzheimer’s disease (AD) patients. Here we investigate the effects of purple sweet potato anthocyanins (PSPA), the known strong free radical scavengers, on Aβ toxicity in PC12 cells. The results showed that pretreatment of PC12 cells with PSPA reduced Aβ-induced toxicity, intracellular reactive oxygen species (ROS) generation and lipid peroxidation dose-dependently. In parallel, cell apoptosis triggered by Aβ characterized with the DNA fragmentation and caspase-3 activity were also inhibited by PSPA. The concentration of intracellular Ca2+ and membrane potential loss associated with cell apoptosis were attenuated by PSPA. These results suggested that PSPA could protect the PC-12 cell from Aβ-induced injury through the inhibition of oxidative damage, intracellular calcium influx, mitochondria dysfunction and ultimately inhibition of cell apoptosis. The present study indicates that PSPA may be a promising approach for the treatment of AD and other oxidative-stress-related neurodegenerative diseases.

Keywords

PSPA Amyloid β peptide (Aβ) Oxidative stress Reactive oxygen species (ROS) Apoptosis PC12 cells 

Abbreviations

PSPA

Purple sweet potato anthocyanins

β-Amyloid

AD

Alzheimer’s disease

PC12

Pheochromocytoma cells

DMSO

Dimethylsulfoxide

DCF-DA

Dichlorofluorescin diacetate

MDA

Malonyl dialdehyde

MTT

3(4,5-dimethylthiazol-2yl)2,5-diphenyl-2H-tetrazolium bromide

OD

Optical density

PBS

Phosphate-buffered saline

ROS

Reactive oxygen species

LPO

Lipid peroxidation

RFU

Relative fluorescence unit

[Ca2+]i

Changes in intracellular free calcium levels

Notes

Acknowledgments

This work was supported by a grant from the Science and Technology Bureau of Qingdao (No. 03-2-JZ-03) and the Science Foundation of Shandong Provincial Educational Department, China (Grant No. J04E17).

References

  1. 1.
    Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 298:789–791CrossRefPubMedGoogle Scholar
  2. 2.
    Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG (2003) Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300(5618):486–489CrossRefPubMedGoogle Scholar
  3. 3.
    Butterfield DA, Drake J, Pocernich C, Castegna A (2001) Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid beta-peptide. Trends Mol Med 7(12):548–554CrossRefPubMedGoogle Scholar
  4. 4.
    Behl C (1997) Amyloid beta-protein toxicity and oxidative stress in Alzheimer’s disease. Cell Tissue Res 290(3):471–480CrossRefPubMedGoogle Scholar
  5. 5.
    Butterfield DA, Castegna A, Lauderback CM, Drake J (2002) Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer’s disease brain contribute to neuronal death. Neurobiol Aging 23(5):655–664CrossRefPubMedGoogle Scholar
  6. 6.
    Bezprozvanny I, Mattson MP (2008) Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci 31(9):454–463CrossRefPubMedGoogle Scholar
  7. 7.
    Mancuso M, Orsucci D, Siciliano G, Murri L (2008) Mitochondria, mitochondrial DNA and Alzheimer’s disease. What comes first? Curr Alzheimer Res 5(5):457–468CrossRefPubMedGoogle Scholar
  8. 8.
    Zhao B (2009) Natural antioxidants protect neurons in Alzheimer’s disease and Parkinson’s disease. Neurochem Res 34(4):630–638CrossRefPubMedGoogle Scholar
  9. 9.
    Kähkönen MP, Heinonen M (2003) Antioxidant activity of anthocyanins and their aglycons. J Agric Food Chem 51(3):628–633CrossRefPubMedGoogle Scholar
  10. 10.
    Prior RL, Wu X (2006) Anthocyanins: structural characteristics that result in unique metabolic patterns and biological activities. Free Radic Res 40(10):1014–1028CrossRefPubMedGoogle Scholar
  11. 11.
    Galvano F, La Fauci L, Vitaglione P, Fogliano V, Vanella L, Felgines C (2007) Bioavailability, antioxidant and biological properties of the natural free-radical scavengers cyanidin and related glycosides. Ann Ist Super Sanita 43(4):382–393PubMedGoogle Scholar
  12. 12.
    Wang H, Cao G, Prior RL (1997) Oxygen radical absorbing capacity of anthocyanins. J Agric Food Chem 45:304–309CrossRefGoogle Scholar
  13. 13.
    Wu X, Cao G, Prior RL (2002) Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. J Nutr 132(7):1865–1871PubMedGoogle Scholar
  14. 14.
    Talavéra S, Felgines C, Texier O, Besson C, Manach C, Lamaison JL, Rémésy C (2004) Anthocyanins are efficiently absorbed from the small intestine in rats. J Nutr 134(9):2275–2279PubMedGoogle Scholar
  15. 15.
    Philpott M, Gould KS, Lim C, Ferguson LR (2004) In situ and in vitro antioxidant activity of sweet potato anthocyanins. J Agric Food Chem 52(6):1511–1513CrossRefPubMedGoogle Scholar
  16. 16.
    Steed LE, Truong VD (2008) Anthocyanin content, antioxidant activity, and selected physical properties of flowable purple-fleshed sweetpotato purees. J Food Sci 73(5):S215–S221CrossRefPubMedGoogle Scholar
  17. 17.
    Suda I, Oki T, Masuda M, Nishiba Y, Furuta S, Matsugano K, Sugita K, Terahara N (2002) Direct absorption of acylated anthocyanin in purple-fleshed sweet potato into rats. J Agric Food Chem 50(6):1672–1676CrossRefPubMedGoogle Scholar
  18. 18.
    Harada K, Kano M, Takayanagi T, Yamakawa O, Ishikawa F (2004) Absorption of acylated anthocyanins in rats and humans after ingesting an extract of Ipomoea batatas purple sweet potato tuber. Biosci Biotechnol Biochem 68(7):1500–1507CrossRefPubMedGoogle Scholar
  19. 19.
    Kano M, Takayanagi T, Harada K, Makino K, Ishikawa F (2005) Antioxidative activity of anthocyanins from purple sweet potato, Ipomoera batatas cultivar Ayamurasaki. Biosci Biotechnol Biochem 69(5):979–988CrossRefPubMedGoogle Scholar
  20. 20.
    Jang JH, Surh YJ (2003) Protective effect of resveratrol on beta-amyloid-induced oxidative PC12 cell death. Free Radic Biol Med 34(8):1100–1110CrossRefPubMedGoogle Scholar
  21. 21.
    Le Bel C, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231CrossRefGoogle Scholar
  22. 22.
    Mihara M, Uchiama M (1978) Determination of malonaldheyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86:271–278CrossRefPubMedGoogle Scholar
  23. 23.
    Telford WG, King LE, Fraker PJ (1991) Evaluation of glucocorticoid-induced DNA fragmentation in mouse thymocytes by flow cytometry. Cell Prolif 24(5):447–459CrossRefPubMedGoogle Scholar
  24. 24.
    Aoshima H, Satoh T, Sakai N, Yamada M, Enokido Y, Ikeuchi T, Hatanaka H (1997) Generation of free radicals during lipid hydroperoxide-triggered apoptosis in PC12h cells. Biochim Biophys Acta 1345(1):35–42PubMedGoogle Scholar
  25. 25.
    Zhang Y, Zhao B (2003) Green tea polyphenols enhance sodium nitroprusside-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. J Neurochem 86(5):1189–1200PubMedCrossRefGoogle Scholar
  26. 26.
    Lorenzo A, Yankner BA (1996) Amyloid fibril toxicity in Alzheimer’s disease and diabetes. Ann N Y Acad Sci 777:89–95CrossRefPubMedGoogle Scholar
  27. 27.
    Tohda C, Tamura T, Matsuyama S, Komatsu K (2006) Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicus. Br J Pharmacol 149(5):532–541CrossRefPubMedGoogle Scholar
  28. 28.
    Hodnick WF, Kung FS, Roettger WJ, Bohmont CW, Pardini RS (1986) Inhibition of mitochondrial respiration and production of toxic oxygen radicals by flavonoids. A structure–activity study. Biochem Pharmacol 35:2345–2357CrossRefPubMedGoogle Scholar
  29. 29.
    Hodnick WF, Milosavljevic EB, Nelson JH, Pardini RS (1998) Electrochemistry of flavonoids: relationships between redox potentials, inhibition of mitochondrial respiration, and production of oxygen radicals by flavonoids. Biochem Pharmacol 37:2607–2611CrossRefGoogle Scholar
  30. 30.
    Miura YH, Tomita I, Watanabe T, Hirayama T, Fukui S (1998) Active oxygens generation by flavonoids. Biol Pharm Bull 21:93–96PubMedGoogle Scholar
  31. 31.
    Praticò D, Uryu K, Leight S, Trojanoswki JQ, Lee VM (2001) Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci 21(12):4183–4187PubMedGoogle Scholar
  32. 32.
    Montiel T, Quiroz-Baez R, Massieu L, Arias C (2006) Role of oxidative stress on beta-amyloid neurotoxicity elicited during impairment of energy metabolism in the hippocampus: protection by antioxidants. Exp Neurol 200(2):496–508CrossRefPubMedGoogle Scholar
  33. 33.
    Eckert A, Marques CA, Keil U, Schüssel K, Müller WE (2003) Increased apoptotic cell death in sporadic and genetic Alzheimer’s disease. Ann N Y Acad Sci 1010:604–609CrossRefPubMedGoogle Scholar
  34. 34.
    He LM, Chen LY, Lou XL, Qu AL, Zhou Z, Xu T (2002) Evaluation of beta-amyloid peptide 25–35 on calcium homeostasis in cultured rat dorsal root ganglion neurons. Brain Res 939(1–2):65–75CrossRefPubMedGoogle Scholar
  35. 35.
    Canevari L, Abramov AY, Duchen MR (2004) Toxicity of amyloid beta peptide: tales of calcium, mitochondria, and oxidative stress. Neurochem Res 29(3):637–650CrossRefPubMedGoogle Scholar
  36. 36.
    Reddy PH (2007) Mitochondrial dysfunction in aging and Alzheimer’s disease: strategies to protect neurons. Antioxid Redox Signal 9(10):1647–1658CrossRefPubMedGoogle Scholar
  37. 37.
    Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H (2004) ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease. Science 304(5669):448–452CrossRefPubMedGoogle Scholar
  38. 38.
    Okajima T, Nakamura K, Zhang H, Ling N, Tanabe T, Yasuda T, Rosenfeld RG (1992) Sensitive colorimetric bioassays for insulin-like growth factor (IGF) stimulation of cell proliferation and glucose consumption: use in studies of IGF analogs. Endocrinology 130(4):2201–2212CrossRefPubMedGoogle Scholar
  39. 39.
    Harada J, Sugimoto M (1999) Activation of caspase-3 in beta-amyloid-induced apoptosis of cultured rat cortical neurons. Brain Res 842(2):311–323CrossRefPubMedGoogle Scholar
  40. 40.
    Heo HJ, Lee CY (2005) Strawberry and its anthocyanins reduce oxidative stress-induced apoptosis in PC12 cells. J Agric Food Chem 53(6):1984–1989CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Junli Ye
    • 1
  • Xiangjun Meng
    • 2
  • Chunling Yan
    • 1
  • Chunbo Wang
    • 3
  1. 1.Department of PathophysiologyMedical College, Qingdao UniversityQingdaoChina
  2. 2.Department of Psychological ConsultationNo. 7 People’s Hospital of QingdaoQingdaoChina
  3. 3.Department of PharmacologyMedical College, Qingdao UniversityQingdaoChina

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