Protective Effect of Acanthopanax senticosus on Oxidative Stress Induced PC12 Cell Death

  • Choi, Soo-Jung (Graduate School of Biotechnology, Korea University) ;
  • Yoon, Kyung-Young (Department of Food and Nutrition, Yeungnam University) ;
  • Choi, Sung-Gil (Division of Applied Life Science, Institute of Agriculture and Life Sciences, Gyeongsang National University) ;
  • Kim, Dae-Ok (Department of Food Science and Technology, Institute of Life Science and Resources, Kyung Hee University) ;
  • Oh, Se-Jong (Department of Animal Science, Institute of Agriculture Science and Technology, Chonnam National University) ;
  • Jun, Woo-Jin (Department of Food and Nutrition, Chonnam National University) ;
  • Shin, Dong-Hoon (Graduate School of Biotechnology, Korea University) ;
  • Cho, Sung-Hwan (Division of Applied Life Science, Institute of Agriculture and Life Sciences, Gyeongsang National University) ;
  • Heo, Ho-Jin (Division of Applied Life Science, Institute of Agriculture and Life Sciences, Gyeongsang National University)
  • Published : 2007.12.31


Epidemiologic studies have shown important relationships between oxidative stress and Alzheimer's disease (AD) brain. In this study, free radical scavenging activity and neuronal cell protection effect of aqueous methanol extracts of Acanthopanax senticosus (A. senticosus) were examined. $H_2O_2$-induced oxidative stress was measured using 2',7'-dichlorofluorescein diacetate (DCF-DA) assay. Pretreatment with the phenolics of A. senticosus prevented oxidative injury against $H_2O_2$ toxicity. Since oxidative stress is known to increase neuronal cell membrane breakdown, leading to cell death, lactic dehydrogenase release, and trypan blue exclusion assays were utilized. We found that phenolics of A. senticosus have neuronal cell protection effects. It suggests that the phenolics of A. senticosus inhibited $H_2O_2$-induced oxidative stress and A. senticosus may be beneficial against the oxidative stress-induced risk in AD.


  1. Yankner BA. Mechanisms of neuronal degeneration in Alzheimer's disease. Neuron 16: 921-932 (1996)
  2. Haass C, De Strooper B. The presenilins in Alzheimer's diseaseproteolysis holds the key. Science 286: 916-919 (1999)
  3. Pike CJ, Walenzcewicz AJ, Glabe CG, Cotman CW. In vivo aging of $\beta$-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res. 563: 311-314 (1991)
  4. Loo DT, Copani A, Pike CJ, Whittemore EK, Walencewicz AJ, Cotman CW. Apoptosis is induced by $\beta$-amyloid in cultured neuronervous system neurons. P. Natl. Acad. Sci. USA 90: 7951- 7955 (1993)
  5. Maccioni RB, Munoz JP, Barbeito L. The molecular bases of Alzheimer's disease and other neurodegenerative disorders. Arch. Med. Res. 32: 367-381 (2001)
  6. Huang X, Cuajungco MP, Atwood CS, Hartshom MA, Tyndall JD, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa RC, Saunders AJ, Lim J, Moir RD, Glabe C, Bowden EF, Masters CL, Fairlie DP, Tanzi RE, Bush AI. Cu(II) potentiation of Alzheimer A$\beta$ neurotoxicity. Correlation with cell free hydrogen peroxide production and metal reduction. J. Biol. Chem. 274: 37111-37116 (1999)
  7. Prasad MR, Lovell MA, Yatin M, Dhillon HS, Markesbery WR. Regional membrane phospholipid alterations in Alzheimer's disease. Neurochem. Res. 23: 81-88 (1998)
  8. Youdim KA, Joseph JA. A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: A multiplicity of effects. Free Radical Bio. Med. 30: 583-591 (2001)
  9. Cao Y, Cao R. Angiogenesis inhibited by drinking tea. Nature 398: 381 (1999)
  10. Eberhardt MV, Lee CY, Liu RH. Antioxidant activity of fresh apples. Nature 405: 903-904 (2000)
  11. Park SY, Chang SY, Yook CS, Nohara T. New 3,4-seco-lupane-type triterpene glycosides from Acanthopanax senticosus forma inermis. J. Nat. Prod. 63: 1630-1633 (2000)
  12. Kim HY, Kim K. Protein glycation inhibitory and antioxidative activities of some plant extracts in vitro. J. Agr. Food Chem. 51: 1586-1591 (2003)
  13. Kim DO, Lee CY. Extraction and isolation of polyphenolics. pp. I1.2.1-I1.2.12. In: Current Protocols in Food Analytical Chemistry. Wrolstad RE (ed). Wiley, New York, NY, USA (2002)
  14. Kim DO, Jeong SW, Lee CY. Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chem. 81: 321-326 (2003)
  15. Heo HJ, Cho HY, Hong BS, Kim HK, Heo TR, Kim EK, Kim SK, Kim CJ, Shin DH. Usolic acid of Origanum majorana L. reduces A$\beta$-induced oxidative injury. Mol. Cell 13: 5-11 (2002)
  16. Park KJ, Ha HC, Kim HS, Chiba K, Yeo IK, Lee SY. The neuroprotective and neurotrophic effects of Korean gardenia (Gardenia Jasminoides Ellis) in PC12h cells. Food Sci. Biotechnol. 15: 735- 738 (2006)
  17. Heo HJ, Cho HY, Hong BS, Kim HK, Kim EK, Kim BK, Shin DH. Protective effect of 4',5-dihydroxy-3',6,7-trimethoxyflavone from Artemisia asiatica against A$\beta$-induced oxidative stress in PC12 cells. Amyloid 8: 194-201 (2001)
  18. Chi HY, Lee CH, Kim KH, Kim SL, Chung IM. Induction of apoptotic cell death by red pericarp rice ('Jakwangchalbyeo') extracts. Food Sci. Biotechnol. 15: 534-542 (2006)
  19. Grundman M, Delaney P. Antioxidant strategies for Alzheimer's disease. P. Nutr. Soc. 61: 191-202 (2002)
  20. Kim DO, Lee KW, Lee HJ, Lee CY. Vitamin C equvailent antioxidant capacity (VCEAC) of phenolic phytochemicals. J. Agr. Food Chem. 50: 3713-3717 (2002)
  21. Behl C, Davis JB, Lesley R, Schubert D. Hydrogen peroxide mediates amyloid $\beta$ protein toxicity. Cell 77: 817-827 (1994)
  22. Jang JH, Surh YJ. Protective effect of resveratrol on $\beta$-amyloidinduced oxidative PC12 cell death. Free Radical Bio. Med. 34: 1100-1110 (2003)
  23. Butterfield DA, Koppal T, Subramaniam R, Yatin S. Vitamin E as an antioxidant/free radical scavenger against amyloid $\beta$-peptideinduced oxidative stress in neocortical synaptosomal membranes and hippocampal neurons in culture: Insights into Alzheimer's disease. Rev. Neurosci. 10: 141-149 (1999)
  24. Tsai AL, Palmer G, Xiao G, Swinney DC, Kalmacz RJ. Structural characterization of arachidonyl radicals formed by prostaglandin H synthase-2 and prostaglandin H synthase-1 reconstituted with mangano protoporphyrin IX. J. Biol. Chem. 273: 3888-3894 (1998)
  25. Halliwell B, Gutteridge MMC. Free Radicals in Biology and Medicine. Clarendon, Oxford, UK. pp. 236-248 (1989)
  26. Floyd RA, Carney JM. Free radical damage to protein and DNA: Mechanisms involved and relevant observations on brain undergoing oxidative stress. Ann. Neurol. 32: S22-S27 (1992)
  27. Lyras L, Cairns NJ, Jenner A, Jenner P, Halliwell B. An assessment of oxidative damage to proteins, lipids, and DNA in brains from patients with Alzheimer's disease. J. Neurochem. 68: 2061-2069 (1997)
  28. Behl C. Alzheimer's disease and oxidative stress: Implications for novel therapeutic approaches. Prog. Neurobiol. 57: 301-323 (1999)
  29. Retz W, Gsell W, Munch G, Rosler M, Riederer P. Free radicals in Alzheimer's disease. J. Neural Transm. -Supp. 54: 221-236 (1998)
  30. Cohen GM. Caspases: The executioners of apoptosis. Biochem. J. 326: 1-16 (1997)
  31. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, King CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, Munday NA, Raju SM, Smulson ME, Yamin TT, Yu VL, Douglas K. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376: 37-43 (1995)
  32. Bergeron L, Yuan J. Sealing one's fate: Control of cell death in neurons. Curr. Opin. Neurobiol. 8: 55-63 (1998)
  33. Pettmann B, Henderson CE. Neuronal cell death. Neuron 20: 633- 647 (1998)
  34. Schulz JB, Weller M, Moskowitz MA. Caspases as treatment targets in stroke and neurodegenerative diseases. Ann. Neurol. 45: 421-429 (1999)<421::AID-ANA2>3.0.CO;2-Q
  35. Green DR. Apoptotic pathways: The roads to run. Cell 94: 695-698 (1998)
  36. Kroemer G, Reed JC. Mitochondrial control of cell death. Nat. Med. 6: 513-519 (2000)
  37. Cha JD, Jeong MR, Lee YE. Induction of apoptosis in human oral epidermoid carcinoma cells by essential oil of Chrysanthemum boreale Makino. Food Sci. Biotechnol. 14: 350-354 (2005)
  38. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X. Cytochrome a and dATP-dependent formation of Apaf-1/Caspase-9 complex initiates an apoptotic protease cascade. Cell 91: 479-489 (1997)
  39. Saleh A, Srinivasula SM, Acharya S, Fishel R, Alnemri ES. Cytochrome c and dATP-dependent oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation. J. Biol. Chem. 274: 17941- 17945 (1999)
  40. Stridh H, Kimland M, Jones DP, Orrenius S, Hampton MB. Cytochrome c release and caspase activation in hydrogen peroxide and tributylin-induced apoptosis. FEBS Lett. 429: 351-355 (1998)
  41. Gruss-Fischer T, Fabian I. Protection by ascorbic acid from denaturation and release of cytochrome c, alteration of mitochondrial membrane potential and activation of multiple caspase induced by H2O2, in human leukemia cells. Biochem. Pharmacol. 63: 1325- 1335 (2002)
  42. Shalit F, Sredni B, Stern L, Kott E, Huberman M. Elevated interleukin-6 secretion levels by mononuclear cells of Alzheimer's patients. Neurosci. Lett. 174: 130-132 (1994)
  43. Harman D. A hypothesis on the pathogenesis of Alzheimer's disease. Ann. NY Acad. Sci. 786: 152-168 (1996)
  44. Selkoe DJ. Cell biology of the amyloid $\beta$-protein precursor and the mechanism of Alzheimer's disease. Annu. Rev. Cell Biol. 10: 373- 403 (1994)
  45. Gregori L, Hainfeld JF, Simon MN, Goldgaber D. Binding of amyloid beta protein to the 20 S proteasome. J. Biol. Chem. 272: 58-62 (1997)
  46. Nishibe S, Kinoshita H, Takeda H, Okano G. Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmaceutical effect in chronic swimming stressed rats. Chem. Pharm. Bull. 38: 1763-1765 (1990)
  47. Jung HJ, Park HJ, Kim RG, Shin KM, Ha JH, Choi JW, Kim HJ, Lee YS, Lee KT. In vivo anti-iflammatory and antinociceptive effects of liriodendrin isolated from the stem bark of Acanthopanax senticosus. Planta Med. 69: 610-616 (2003)