In vitro neuroprotective potential of four medicinal plants against rotenone-induced toxicity in SH-SY5Y neuroblastoma cells

BMC Complementary and Alternative Medicine

Vanessa Steenkamp¹  Jacob John van Tonder¹  Keabetswe Seoposengwe¹ 

[1] Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Arcadia, Pretoria, South Africa

关键词: Zanthoxylum capense;    Scadoxus puniceus;    Rotenone;    Reactive oxygen species (ROS);    Neuroprotection;    Mitochondrial membrane potential;    Lannea schweinfurthii;    Glutathione;    Crinum bulbispermum;    Caspase-3;   

Others  :  1220454
DOI  :  10.1186/1472-6882-13-353

 received in 2013-10-09, accepted in 2013-12-05,  发布年份 2013

【 摘 要 】

Background

Lannea schweinfurthii, Zanthoxylum capense, Scadoxus puniceus and Crinum bulbispermum are used traditionally to treat neurological disorders. The aim of this study was to evaluate the cytoprotective potential of the four plants, after induction of toxicity using rotenone, in SH-SY5Y neuroblastoma cells.

Methods

Cytotoxicity of the plant extracts and rotenone was assessed using the sulforhodamine B (SRB) assay. Fluorometry was used to measure intracellular redox state (reactive oxygen species (ROS) and intracellular glutathione content), mitochondrial membrane potential (MMP) and caspase-3 activity, as a marker of apoptotic cell death.

Results

Of the tested plants, the methanol extract of Z. capense was the least cytotoxic; LC₅₀ 121.3 ± 6.97 μg/ml, while S. puniceus methanol extract was the most cytotoxic; LC₅₀ 20.75 ± 1.47 μg/ml. Rotenone reduced intracellular ROS levels after 24 h exposure. Pre-treating cells with S. puniceus and C. bulbispermum extracts reversed the effects of rotenone on intracellular ROS levels. Rotenone exposure also decreased intracellular glutathione levels, which was counteracted by pre-treatment with any one of the extracts. MMP was reduced by rotenone, which was neutralized by pre-treatment with C. bulbispermum ethyl acetate extract. All extracts inhibited rotenone-induced activation of caspase-3.

Conclusion

The studied plants demonstrated anti-apoptotic activity and restored intracellular glutathione content following rotenone treatment, suggesting that they may possess neuroprotective properties.

【 授权许可】

   
2013 Seoposengwe et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Thomas B, Beal MF: Parkinson’s disease. Hum Mol Genet 2007, 16:183-194.
• [2]Van Den Eeden SK, Tanner CM, Bernstein AL, Leimpeter A, Bloch DA, Nelson LM: Incidence of Parkinson’s disease: variation by age, gender and race/ethnicity. Am J Epidemiol 2003, 157:1015-1022.
• [3]de Lau LM, Breteler MM: Epidemiology of Parkinson’s disease. Lancet Neurol 2006, 5:25-35.
• [4]Maguire-Zeiss KA, Federoff HJ: Convergent pathobiologic model of Parkinson’s disease. Ann NY Acad Sci 2003, 99:152-166.
• [5]Joshi S, Guleria R, Pan J, DiPette D, Singh US: Retinoic acid receptors and tissue-transglutaminase mediate short-term effect of retinoic acid on migration and invasion of neuroblastoma SH-SY5Y cells. Oncogene 2006, 25:240-247.
• [6]Ciccarone V, Spengler BA, Meyers MB, Biedler JL, Ross RA: Phenotypic diversification in human neuroblastoma cells: expression of distinct neural crests lineages. Cancer Res 1989, 49:219-225.
• [7]Höglinger GU, Carrard G, Michel PP, Medja F, Lombès A, Ruberg M, Friguet B, Hirsch EC: Dysfunction of mitochondrial complex I and the proteasome: interactions between two biochemical deficits in a cellular model of Parkinson’s disease. J Neurochem 2003, 86:1297-1307.
• [8]Ruipérez V, Darios F, Davletov B: Alpha-synuclein, lipids and Parkinson’s disease. Prog Lipid Res 2010, 49:420-428.
• [9]Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, Miller GW, Yagi T, Matsuno-Yagi A, JT G: Mechanism of toxicity in rotenone models of Parkinson’s disease. J Neurosci 2003, 23:10756-10764.
• [10]Schuler F, Casida JE: Functional coupling of PSST and ND1 subunits in NADH: ubiquinone oxidoreductase established by photoaffinity labeling. Biochim Biophys Acta 2001, 1506:79-87.
• [11]Hu BY, Weick JP, Yu J, Ma LX, Zhang XQ, Thomson JA, Zhang SC: Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci U S A 2010, 107:4335-4340.
• [12]Hu S, Han R, Mak S, Han Y: Protection against 1-methyl-4-phentlpyridinium ion (MPP+)-induced apoptosis by water extract of ginseng (Panax ginseng C.A Meyer) in SH-SY5Y cells. J Ethnopharmacol 2011, 135:34-42.
• [13]Skibinski G, Finkbeiner S: Drug discovery in Parkinson’s disease: update and developments in the use of cellular models. Int J High Throughput Screen 2011, 2:15-25.
• [14]Chung V, Liu L, Bian Z, Zhao Z, Leuk FW, Kum WF, Gao J, Li M: Efficacy and safety of herbal medicines for idiopathic Parkinson’s disease: a systematic review. Mov Disord 2006, 21:1709-1715.
• [15]Martorana A, Esposito Z, Koch G: Beyond the cholinergic hypothesis: do current drugs work in alzheimer’s disease? CNS Neurosci Ther 2010, 16:235-245.
• [16]Kim J, Wong PKY: Oxidative stress is linked to ERK1/2-p16 signalling-mediated growth defect in ATM-deficient astrocytes. J Biol Chem 2009, 284:14396-14404.
• [17]Doo AR, Kim SN, Park JY, Cho KH, Hong J, Eun-Kyung K, Moon SK, Jung WS, Lee H, Jung JH, Park HJ: Neuroprotective effects of an herbal medicine, Yi-Gan San on MPP+/ MPTP-induced cytotoxicity in vitro and in vivo. J Ethnopharmacol 2010, 131:433-442.
• [18]Ferry P, Johnson M, Wallis P: Use of complementary therapies and non-prescribed medication in patients with Parkinson’s disease. Postgrad Med J 2002, 78:612-614.
• [19]Mabogo DEN: The ethnobotany of the VhaVenda. Pretoria, South Africa: MSc thesis, University of Pretoria; 1990.
• [20]Van Wyk B-E, Gericke N: People’s plants: a guide to useful plants of southern Africa. Pretoria: Briza Publications; 2000.
• [21]Watt JM, Breyer-Brandwijk MG: The medicinal and poisonous plants of Southern and Eastern Africa. 2nd edition. London: Livingstone; 1962.
• [22]Veale DJH, Furman KI, Oliver DW: South African traditional herbal medicines used during pregnancy and child-birth. J Ethnopharmacol 1992, 36:185-191.
• [23]Oloyede GK, Oke JM, Raji Y, Olugbade TA: Antioxidant and anticonvulsant alkaloids in Crinum ornatum bulb extract. World J Chem 2010, 5:26-31.
• [24]Vichai V, Kirtikara K, Sulforhodamine B: Colorimetric assay for cytotoxicity screening. Nat Protoc 2006, 1:1112-1116.
• [25]Faust K, Gehrke S, Yang Y, Yang L, Beal MF, Lu B: Neuroprotective effects of compounds with antioxidant and anti-inflammatory properties in a Drosophilia model of Parkinson’s disease. BMC Neurosci 2009, 10:1-17. BioMed Central Full Text
• [26]Shaykhalishahi H, Yazdanparast R, Ha HH, Chang YT: Inhibition of H2O2-induced neuroblastoma cell cytotoxicity by a triazine derivative, AA3E2. Eur J Pharmacol 2009, 622:1-6.
• [27]Nair JJ, Rárová L, Strnad M, Bastida J, van Staden J: Apoptosis-inducing effects of distichamine and narciprimine, rare alkaloids of the plant family Amaryllidaceae. Bioorg Med Chem Lett 2012, 22:6195-6199.
• [28]Sternfeld T, Schmid M, Tischleder A, Mudra S, Schlamp A, Kost BP, Gruber R, Youle M, Bogner JR, Goebel FD: The influence of HIV infection and antiretroviral therapy on the mitochondrial membrane potential of peripheral mononuclear cells. Antiviral Ther 2007, 12:769-778.
• [29]van Tonder JJ: Development of an in vitro mechanistic toxicity screening model using cultured hepatocytes. Pretoria: PhD dissertation, University of Pretoria; 2012.
• [30]Gilgun-Sherki Y, Melamed E, Offen D: Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology 2001, 40:959-975.
• [31]Chauhan V, Chauhan A: Oxidative stress in Alzheimer’s disease. Pathophysiology 2006, 13:195-208.
• [32]Jordan J, Cena V, Prehn JH: Mitochondrial control of neuron death and its role in neurodegenerative disorders. J Physiol Biochem 2003, 59:129-141.
• [33]Louvena N, Cohen JW, Han LY, Talbot K, Wilson RS, Bennett DA, Trojanowski JQ, Arnold SE: Caspase-3 is enriched in postsynaptic densities and increased in Alzheimer’s disease. Am J Pathol 2008, 173:1488-1495.
• [34]Tatton WG, Chalmers-Redman R, Brown D, Tatton N: Apoptosis in Parkinson’s disease: signals for neuronal degradation. Ann Neurol 2003, 53:61-70.
• [35]Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna A, Panov V, Greemamyre JT: hronic systemic pesticide exposure reproduces features of Parkinson’s diseases. Nat Neurosci 2000, 3:1301-1306.
• [36]Swarnkar S, Goswami P, Kamat PK, Gupta S, Patro IK, Singh S, Nath C: Rotenone-induced apoptosis and role of calcium: a study on Neuro-2a cells. Arch Toxicol 2012, 86:1387-1397.
• [37]Moshi MJ, Kamuhabwa A, Mbwambo Z, de Witte P: Cytotoxic screening of some Tanzania medicinal plants. East Central Afr J Pharmaceutical Sci 2003, 6:52-56.
• [38]Patiño LOJ, Prieto RJ, Cuca SLE: Zanthoxylum genus as potential source of bioactive compounds. In Bioactive Compounds in Phytomedicine. Edited by Rasooli I. Rijeka, Croatia: InTech; 2012:185-218.
• [39]Bastida J, Lavilla R, Viladomat F: Chemical and biological aspects of Narcissus alkaloids. Alkaloids Chem Biol 2006, 63:87-179.
• [40]Klein NC, Cunha BA: Tetracyclines. Med Clin North Am 1995, 79:789-801.
• [41]Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi DK, Ischiropoulos H, Przedborski: Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 2002, 22:1763-1771.
• [42]Kremlev SG, Roberts RL, Palmer C: Differential expression of chemokines and chemokine receptors during microglial activation and inhibition. J Neuroimmunol 2004, 149:1-9.
• [43]Keeney PM, Xie J, Capaldi RA, Bennett JP: Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci 2006, 26:5256-5264.
• [44]Perier C, Tieu C, Guégan C, Caspersen C, Jackson-Lewis V, Carelli V, Martinuzzi A, Hirano M, Przedborski S, Vila M: Complex I deficiency primes Bax-dependent neuronal apoptosis through mitochondrial oxidative damage. Proc Natl Acad Sci USA 2005, 102:19126-19131.
• [45]Molina-Jimenez MF, Sanchez-Reus MI, Benedi J: Effect of fraxetin and myricetin on rotenone-induced cytotoxicity in SH-SY5Y cells: comparison with N-acetylcysteine. Eur J Pharmacol 2003, 472:81-87.
• [46]Vrablic AS, Albright CD, Craciunescu CN, Salganik RI, Zeisel SH: Altered mitochondrial function and overgeneration of reactive oxygen species precede the induction of apoptosis by 1-Ο-octadecyl-2-methyl-rac-glycero-3-phosphocholine in p53-defective hepatocytes. FASEB J 2001, 15:1739-1744.
• [47]Gao HM, Liu B, Hong JS: Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 2003, 23:6181-6187.
• [48]Li J, Spletter ML, Johnson DA, Svendsen CN, Johnson JA: Rotenone-induced caspase 9/3-independent and -dependent cell death in undifferentiated human neural stem cells. J Neurochem 2005, 92:462-476.
• [49]Adesina SK: The Nigerian Zanthoxylum: chemical and biological values. AJTCAM 2005, 2:282-301.
• [50]Koshy AS, Anila L, Vijayalaksmi NR: Flavonoids from Garciniacombagia lower lipid levels in hypercholesterlemic rats. Food Chem 2001, 72:289-294.
• [51]Isenberg JS, Klaunig JE: Role of mitochondrial membrane permeability transition (MPT) in rotenone-induced apoptosis in liver cells. Toxicol Sci 2000, 53:340-351.
• [52]Fiorani M, de Sanctis R, Menghinello P, Cucchiarini L, Cellini B, Dachà M: Quercetin prevents glutathione depletion induced by dehydroascorbic acid in rabbit red blood cells. Free Radic Res 2001, 34:639-648.
• [53]Ilavenil S: Hepatoprotective mechanism of Crinum asiaticum L. and lycorine in carbon tetrachloride induced oxidative stress in Swiss albino mice. Thanjavur, India: PhD thesis, Prist University; 2012.
• [54]Kroemer G, Petit PX, Zamzami N, Vayssiere JL, Mignotte B: The biochemistry of programmed cell death. FASEB J 1995, 9:1277-1287.
• [55]Zamzami N, Susin SA, Marchetti P, Hirsch T, Castedo M, Kroemer G: Mitochondrial control of nuclear apoptosis. J Exp Med 1996, 183:1533-1544.
• [56]Chandel NS, Budinger GR, Choe SH, Schumacker PT: Cellular respiration during hypoxia. Role of cytochrome oxidase as the oxygen sensor in hepatocytes. J Biol Chem 1997, 272:18808-18816.
• [57]Thuret G, Chiquet C, Herrag S, Dumollard J-M, Boudard D, Bednarz J, Campos L, Gain P: Mechanisms of staurosporine induced apoptosis in a human corneal endothelial cell line. Brit J Ophthalmol 2003, 87:346-352.
• [58]Chauvin C, De Oliveira F, Ronot X, Mousseau M, Leverve X, Fontaine E: Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells. J Biol Chem 2001, 276:41394-41398.
• [59]Zhu S, Stavrovskaya IG, Drozda M, Kim BY, Ona V, Li M, Sarang S, Liu AS, Hartley DM, Wu DC, Gullans S, Ferrante RJ, Przedborski S, Kristal BS, Friedlander RM: Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 2002, 417:74-78.
• [60]Mansoor TA, Borralho PM, Luo X, Mulhovo S, Rodrigues CM, Ferreira MJ: Apoptosis inducing activity of benzophenanthridine-type alkaloids and 2-arylbenzofuran neolignans in HCT116 colon carcinoma cells. Phytomedicine 2013, 15:923-929.
• [61]Bao MH, Dai W, YJ L, Hu CP: Rutaecarpine prevents hypoxia-reoxygenation-induced myocardial cell apoptosis via inhibition of NADPH oxidases. Can J Physiol Pharmacol 2011, 89:177-186.
• [62]Suematsu N, Hosoda M, Fujimori K: Protective effects of quercetin against hydrogen peroxide-induced apoptosis in human neuronal SH-SY5Y cells. Neurosci Lett 2011, 504:223-227.
• [63]Xi J, Zhang B, Luo F, Liu J, Yang T: Quercetin protects neuroblastoma SH-SY5Y cells against oxidative stress by inhibiting expression of Krüppel-like factor 4. Neurosci Lett 2012, 527:115-120.
• [64]Yamamoto S, Seta K, Morisco C, Vatner SF, Sadoshima J: Chelerythrine rapidly induces apoptosis through generation of reactive oxygen species in cardiac myocytes. J Mol Cell Cardiol 2001, 33:1829-1848.
• [65]Miyahara Y, Komiya T, Katsuzaki H, Imai K, Nakagawa M, Ishi Y, Hibasami H: Sesamin and episesamin induce apoptosis in human lymphoid leukemia Molt 4B cells. Int J Mol Med 2000, 6:43-46.
• [66]McNulty J, Nair JJ, Codina C, Bastida J, Pandey S, Gerasimoff J, Griffin C: Selective apoptosis-inducing activity of crinum-type Amaryllidaceae alkaloids. Phytochemistry 2009, 68:1068-1074.
• [67]Nair S, Singh SV, Krishan A: Flow cytometric monitoring of glutathione content and anthracycline retention in tumor cells. Cytometry 1991, 12:336-342.