Studies on biological effect of lycopene on Hippocampus of hyperlipemia rats
Yao-Chi Zeng, Min-Yu Hu, Shu-Lin Qu, Liang Zeng
DOI: 10.4236/health.2009.11003   PDF    HTML     5,990 Downloads   11,650 Views   Citations


Objective: This study investigated into the ef-fect of lycopene on expression of APP, bax and bcl-2 in hippocampal CA1 region of rats with hyperlipidemia. Methods: By total cholesterol (TC) and body weight, 48 adult male SD rats were randomized into six groups, a normal control group, fed with basic feed; a high-fat model group, fed with high-fat feed; a positive drug control group, fed with high-fat feed and administrated with fluvastatin sodium at a dose of 10 mg?kg?bw-1?d-1 by gastric perfusion; and lycopene groups at three dose levels, fed with high-fat feed and administrated with lycopene at doses of 11, 22 and 44 mg?kg?bw-1?d-1 respec-tively also by gastric perfusion. Caudal venous blood samples of rats in all groups were taken at week 0, week 1 and week 3 after the experiment started so as to assay TC, TG, LDL-C and HDL-C; at the end of the experiment, rat brains were taken and sections of the hippocampal CA1 re-gion were prepared. Expression of APP, bax and bcl-2 in the CA1 region was determined by im-munohistochemical methods and morphologi-cal examination was carried out. Results: One week after fed with high-fat feed, models of hy-perlipidemia rats were established; at the end of experiment, hippocampal APP and bax expres-sion was enhanced while bcl-2 expression was significantly weakened (p<0.05); to rats with hyperlipidemia, both lycopene and fluvastatin sodium could reduce TC, TG and LDL-C, inhibit expression of hippocampal APP and bax and promote expression of bcl-2 (p<0.05). Conclu- sion: Lycopene down-regulates the expression of bax and up-regulates that of bcl-2 mainly by reducing serum TC and LDL-C and weakening expression of APP in the hippocampal CA1 re-gion of rats with hyperlipidemia, thereby main-taining normal morphology of hippocampal neurons and facilitating the protection of the brain.

Share and Cite:

Zeng, Y. , Hu, M. , Qu, S. and Zeng, L. (2009) Studies on biological effect of lycopene on Hippocampus of hyperlipemia rats. Health, 1, 8-16. doi: 10.4236/health.2009.11003.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] S. Agarwal and A. V. Rao, (2000) Tomato lycopene and its role in human health and chronic diseases, CMAJ, 163, 739-744.
[2] T. H. Rissanen, S. Voutilainen, K. Nyyssonen, R. Sa-lonen, G. A. Kaplan, and J. T. Salonen, (2003) Serum lycopene concentrations and carotid atherosclerosis: The Kuopio ischaemic heart disease risk factor study, Am JClin Nutr, 77, 133-138.
[3] K. Canene-Adams, J. K. Campbell, S. Zaripheh, E. H. Jeffery, and J. W. Erdman Jr., (2005) The tomato as a functional food, J Nutr, 135, 1226-1230.
[4] A. O. Omoni and R. E. Aluko, (2005) The anti-carcino-genic and anti-atherogenic effects of copene: A review, Trends Food Sci Tech, 16, 344-350.
[5] K. Klipstein-Grobushch, L. J. Launer, J. M. Geleijnse, H. Boeing, A. Hofman, and J. C. Witteman, (2000) Serum carotenoids and atherosclerosis, The Rotterdam Study. Atherosclerosis, 148, 49-56.
[6] T. Rissanen, S. Voutilainen, K. Nyyssonen, R. Salonen, G. A. Kaplan, and J. T. Salonen, (2003) Serum lycopene concentration and carotid atherosclerosis: The Kuopio ischaemic heart disease risk factor study, Am. J. Clin. Nutr, 77, 133-138.
[7] M. Y. Hu, Y. L. Li, Z. Q. Liu, S. L. Ou, Y. M. Huang, (2007) The protective effect of lycopene on atherogene-sis in rabbits, Acta Nutrimenta Sinica, 29, 498-502.
[8] M. Y. Hu, Y. L. Li, C. H. Jiang, Z. Q. Liu, S. L. Qu, Y. M. Huang, (2008) Comparison of lycopene and fluvas-tatin effects on atherosclerosis induced by a high-fat diet in rabbits, Nutrition, 24, 1030-1038.
[9] S. Bodovitz and W. L. Klein, (1996) Cholesterol modu-lates alpha-secretase cleavage of amyloid precursor pro-tein, J Biol Chem, 21, 4436-4440.
[10] M. Kivipelto, E. L. Helkala, M. P. Laakso, T. H?nninen, M. Hallikainen, K. Alhainen, H. Soininen, J. Tuomilehto, and A. Nissinen, (2001) Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study, BMJ, 322, 1447-1451.
[11] K. Sleegers, N. Brouwers, I. Gijselinck, J. Theuns, D. Goossens, J. Wauters, J. Del-Favero, M. Cruts, C. M. van Duijn, and C. van Broeckhoven, (2006) APP duplication is sufficient to cause early onset Alzheimer’s dementia with cerebral amyloid angiopathy. Brain, 129, 2977-2983.
[12] A. V. Rao and L. G. Rao, (2007) Carotenoids and human health, Pharmacological Research, 55, 207-216.
[13] C. K. Jain, S. Agarwal, and A. V. Rao, (1999) The effect of dietary lycopene on bioavailability, tissue distribution, in vivo antioxidant properties and colonic preneoplasia in rats, Nutrihon Research, 19, 1383-1391.
[14] C. J. Foy, A. P. Passmore, M. D. Vahidassr, I. S. Young, and J. T. Lawson, (1999) Plasma chain-breaking antioxi-dants in Alzheimer’s disease, vascular dementia and Parkinson’s disease, Q JM, 92, 39-45.
[15] P. R. Deepa and T. P. Varalakshmi, (2004) Atheropro-tective effect of exogenous heparin-derivative treatment on the aortic disturbances and lipoprotein oxidation in hypercholesterolemic diet fed rats, Clinica Chimica Acta, 12, 119-130.
[16] F. Quang, B. -J. Lee, W. Lee, and H. -K. Han, (2009) Pharmacokinetic drug interaction between fexofenadine and fluvastatin mediated by organic anion-transporting polypeptides in rats, European Journal of Pharmaceutical Sciences.
[17] M. Itagaki, A. Takaguri, S. Kano, S. Kaneta, K. Ichihara, and K. Satoh, (2009) Possible mechanisms underlying statin-induced skeletal muscletoxicity in L6 fibroblasts and in rats, J Pharmacol Sci, 109, 94-101.
[18] T. D. Watson, R. F. Butterwick, M. McConnell, and P. J. Markwell, (1995) Development of methods for analyzing plasma lipoprotein concentrations and associated enzyme activities and their use to measure the effects of preg-nancy and lactation in cats, Am J Vet Res, 56, 289-296.
[19] W. T. Friedewald, R. I. Levy, and D. S. Fredrickson, (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge, Clin Chem, 18, 499-502.
[20] (2008) Acceleration of diabetic wound healing withchi-tosan-crosslinked collagen sponge containing recombi-nant human acidic fibroblast growth factor inhealing- impaired STZ diabetic rats, Life Sciences, 82, 190-204.
[21] S. H. Peng, H. Deng, D. Y. Feng, and H. Zheng, (2004) Expression of HSP 70 and caspase 3 and their signifi-cance in hepatocellular carcinoma tissues, World Chinese Journal of Digestology, 12, 782-784.
[22] L. J. Launer, L. R. White, H. Petrovitch, G. W. Ross, and J. D. Curb, (2001) Cholesterol and neuropathologic markers of AD: A population2-based autopsy study, Neurology, 57, 1447-1452.
[23] L. Puglielli, R. E. Tanzi, and D. M. Kovacs, (2003) Alz-heimer’s disease: The cholesterol connection, Nat Neu-rosci, 6, 345-351.
[24] M. Burns and K. Duff, (2002) Cholesterol in Alzheimer’s disease and Tauopathy, Ann N Y Acad Sci, 977, 367- 375.
[25] K. Yanagisawa, (2002) Cholesterol and pathological processes in Alzheimer’s disease, J Neurosci Res, 70, 361-366.
[26] A. E. Roher, Y. M. Kuo, K. M. Kokjohn, M. R. Emmerling, S. Gracon, (1999) Amyloid and lipids in the pathology of Alzheimer’s disease, Amyloid, 6, 136-145.
[27] G. Lesser, K. Kandiah, L. S. Libow, A. Likourezos, B. Breuer, D. Marin, R. Mohs, V. Haroutunian, and R. Neufeld, (2001) Elevated serum total and LDL choles-terol in very old patients with Alzheimer’s disease, De-ment Geriatr Cogn Disord, 12, 138-145.
[28] W. G. Wood, G. P. Eckert, U. Igbavboa, and W. E. Müller, (2003) Amyloid beta-protein interactions with membranes and cholesterol: causes or casualties of Alz-heimer’s disease, Biochim Biophys Acta, 1610, 281-290.
[29] P. P. Zandi, D. L. Sparks, A. S. Khachaturian, J. Tschanz, M. Norton, M. Steinberg, K. A. Welsh-Bohmer, and J. C. Breitner, (2005) Cache county study investigators: do statins reduce risk of incident dementia and Alzheimer disease? The cache county study, Arch Gen Psychiatry, 62, 217-224.
[30] C. Kirsch, G. P. Eckert, A. R. Koudinov, and W. E. Müller, (2003) Brain cholesterol, statins and Alzheimer’s disease, Pharmacopsychiatry, 36, S113-119.
[31] I. Masse, R. Bordet, D. Deplanque, A. Al Khedr, F. Rich-ard, C. Libersa, and F. Pasquier, (2005) Lipid lowering agents are associated with a slower cognitive decline in Alzheimer’s disease, Neurol Neurosurg Psychistry, 76, 1624-1629.
[32] J. Marx, (2001) Alzheimer’s disease: BAD for the heart, BAD for the mind, Science, 294, 508-509.
[33] A. Delacourte, (2006) From physiopathology to treat-ment of Alzheimer’s disease, Rev Neurol (Paris), 162, 909-912.
[34] G. Verdile, S. Fuller, C. S. Atwood, S. M. Laws, S. E. Gandy, and R. N. Martins, (2004) The role of beta amy-loid in Alzheimer’s disease: Still a cause of everything or the only one who got caught, Pharmacol Res, 50, 397-409.
[35] D. L. Sparks, S. W. Scheff, J. C. Hunsaker 3rd, H. Liu, T. Landers, D. R. Gross, (1994) Induction of Alzheimer-like β-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol, Exp Neurol, 126, 88-94.
[36] D. L. Sparks, Y. M. Kuo, A. Roher, T. Martin, R. J. Lukas, (2000) Alterations of Alzheimer’s disease in the cholesterol-fed rabbit, including vascular inflammation, Preliminary Observations Ann N Y Acad Sci, 903, 335-344.
[37] L. Li, D. Cao, D. W. Garber, H. Kim, and K. Fukuchi, (2003) Association of aortic atherosclerosis with cerebral beta- amyloidosis and learning deficits in a mouse model of Alzheimer’s disease, Am J Pathol, 163, 2155-2161.
[38] M. Simons, P. Keller, B. De Strooper, K. Beyreuther, C. G. Dotti, and K. Simons, (1998) Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons, Neurobiology, 95, 6460-6464.
[39] L. Conboy, K. J. Murphy, and C. M. Regan, (2005) Amyloid precursor protein expression in the rat hippo-campal dentate gyrus modulates during memory con-solidation, J Neurochem., 95, 1677-1688.
[40] J. Hardy and D. J. Selkoe, (2002) The amyloid hypothe-sis of Alzheimer’s disease: progress and problems on the road to therapeutics, Science, 297, 353-356.
[41] F. S. Shie, L. W. Jin, D. G. Cook, J. B. Leverenz, and R. C. LeBoeuf, (2002) Diet-induced hypercholesterolemia enhances brain A beta accumulation in transgenic mice, Neuroreport, 13, 455-459.
[42] A. Rovelet-Lecrux, D. Hannequin, G. Raux, N. Le Meur, A. Laquerrière, A. Vital, C. Dumanchin, S. Feuillette, A. Brice, M. Vercelletto, F. Dubas, T. Frebourg, D. Cam-pion, (2006) APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy, Nat Genet, 38, 24-26.
[43] P. N. Shevtsov, E. F. Shevtsova, G. S. Burbaeva, S. O. Bachurin, (2006) Disturbed assembly of human cerebral mierotubules in Alzheimer’s disease, Bull Exp Biol Med, 141, 265-268.
[44] A. Fuso, I. Seminara, R. A. Cavallaro, F. D’Anselmi, S. Scarpa, (2005) S-aden0sylmethi0nine/homocysteine cy-cle alterations modify DNA methylation status with con-sequent deregulation of PSI and BACE and beta-amyloid production, Mol Cell Neurosci, 28, 195-204.
[45] E. B. Beeker and A. Bonni, (2004) Cell cycle regulation of neuronal apoptosis in development and disease, Pmg Neumbiol, 72, 1-6.
[46] S. H. Graham and J. Chen, (2001) Programmed cell death in cerebral ischemia, J Cereb Blood Flow Metab, 2l, 99-109.
[47] A. C. Leblane, (2005) The role of apoptotic pathways in Alzheimer’s disease neumdegeneration and cell death, Curr Alzheimer Res, 2, 389-397.
[48] W. P. Li, W. Y. Chan, H. W. Lai, and D. T. Yew, (1997) Terminal DUTP nick end labeling (TUNEL) positive cells in the different regions of the brain in normal aging and Alzheimer patients, Mol Neurosci, 8, 75-82.
[49] S. Shimohama, (2000) Apoptosis in Alzheimer’s disease an update, Apoptosis, 5, 9-16.
[50] S. Shimohama, H. Tanino, and S. Fujimoto, (1999) Changes in caspase expression in Alzheimer’s disease, comparison with development and aging, Biochem Bio-phys Res Commun, 256, 381-384.
[51] F. J. Antonawich, H. J. Federoff, and J. N. Davis, (1999) BCL-2 transduction, using a herpes simplex virus am-plicon, protects hippocampal neurons from transient global ischemia, Exp Neurol, 156, 130-137.
[52] E. ParADis, H. Douillard, M. Koutroumanis, C. Goodyer, and A. LeBlanc, (1996) Amyloid beta peptide of Alzheimer’s diseased down regulates Bcl-2 and up regulates Bax expres-sion in human neurons, Neurosis, 16, 7533- 7539.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.