Neuroprotective Effects of Purslane Seeds against Adverse Effects Induced by Experimental Hyperlipidemia on Frontal Cortex and Cerebellum in Young Male Albino Rats
Background. Hyperlipidemia is characterized by abnormally elevated levels of lipids and is positively associated with cerebrovascular diseases. Alzheimer’s disease (AD) is a chronic brain disorder characterized by cognitive impairment, inflammation, β-amyloid deposition, and vascular damage. Recent studies have shown that high cholesterol levels are linked to the pathology of AD. Purslane seeds are medicinal plants rich in unsaturated fatty acids (omega-3), antioxidants, and fibers. They are known to have antidiabetic and antiatherogenic activities. The aim of this research is to study the structural alterations occurring in the frontal cortex and cerebellum after feeding high cholesterol diet, and the possible protective role of purslane seeds. Materials and methods. Forty male albino rats were used in the study. They were divided into three groups; control group (20 rats), hypercholesterolemic group (10 rats) who were fed the balanced diet supplemented with cholesterol at a dose of 2 gm/100 gm diet, and protected group (10 rats) who were fed the same previous hypercholesterolemic diet concomitant with purslane seed 20% (20 gm/100 ml water). After 3 months, blood samples were collected from all rats for biochemical estimation and fresh specimens were taken from the frontal cortex and cerebellum of each rat and processed for; light microscopic examination using H&E and Orcein stains. Results. Significant increase of serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels in hyperlipidemic rats were detected. Associated structural changes in the frontal cortex of the rats were evident as pyknotic nuclei of degenerated neurons, loss of neuron, dilation and congestion of blood vessels, expanded perivascular space, and increased vacuolar spaces of neuropil. The cerebellar cortex of the rats fed on high cholesterol diet revealed pyknotic nuclei of degenerated neuron and decrease in the number of Purkinje and granule cells compared to the control group. Concomitant administration of purslane seeds revealed evident amelioration of biochemical and most of the structural changes. Conclusion. We concluded that a high cholesterol diet has deleterious biochemical changes associated with structural alteration in the frontal cortex and cerebellum and purslane seeds ameliorate most of these changes.
El Sayed Aly Mohamed Metwally,
Fardous Soror Karawya,
Neuroprotective Effects of Purslane Seeds against Adverse Effects Induced by Experimental Hyperlipidemia on Frontal Cortex and Cerebellum in Young Male Albino Rats, International Journal of Clinical and Experimental Medical Sciences.
Vol. 1, No. 3,
2015, pp. 46-59.
Kruger J, Bowles HR, Jones DA, Ainsworth BE, Kohl HW. Health-related quality of life, BMI and physical activity among US adults (18 years): national physical survey and weight loss survey. Int J Obes. 2002;31:321-327.
Wolf G. After all those years: renal consequences of obesity. Nephrol Dial Transpl. 2003;18:2471-2474.
Xia D, Wu X, Yang Q, Gong J, Zhang Y. Anti-obesity and hypolipidemic effects of a functional formula containing Prumus mume in mice fed high-fat diet. Afr J Biotechnol. 2010;9:2463–2467.
Bell RD, Zlokovic BV. Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer's disease. Acta Neuropathol. 2009;118:103–113.
Deane R, Zlokovic BV. Role of the blood–brain barrier in the pathogenesis of Alzheimer's disease. Curr Alzheimer Res. 2007;4:191–197
Humpel C, Weis C. Nerve growth factor and cholinergic CNS neurons studied in organotypic brain slices: Implication in Alzheimer's disease? J Neural Transm Suppl. 2002;62:253–263.
Heneka MT and O'Banion MK. Inflammatory processes in Alzheimer's disease. J Neuroimmunol. 2007;184: 69–91.
Thirumangalakudi L, Prakasam A, Zhang R, et al. High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice. J Neurochem. 2008;106: 475–485.
Ullrich C, Humpel C. Effects of cholesterol and its 24 S-OH and 25- OH oxysterols on choline acetyltransferase – positive neurons in brain slices. Pharmacology. 2010;86:15-21.
Ullrich C, Pirchl M, Humpel C. Hypercholesterolemia in rats impairs the cholinergic system and leads to memory deficits. Mol Cell Neurosci. 2010;45:408–417.
De Lau LM, Koudstaal PJ, Hofman A, Breteler MM. Serum cholesterol levels and the risk of Parkinson's disease. Am J Epidemiol. 2006;164:998–1002.
Morris MC, Evans DA, Bienias JL, et al. Dietary fats and the risk of incident Alzheimer disease. Arch Neurol. 2003; 60:194–200.
Kumar S, Alagawadi KR, Rao MR. Effect of Argyreia speciosa root extract on cafeteria diet-induced obesity in rats. Ind J Pharmacol. 2011;43:163.
Ellrichmann M, Kapelle M, Ritter PR, et al. Orlistat inhibition of intestinal lipase accurately increase appetite and attenuate post prandial glucagons - like peptide - 7 (7-36)- amide-1 cholesytokinin and peptide yy concentrations. J Clin Endocrinol Metabol. 2008;93:3995–3998.
Radhakrishnan R, Zakaria MN, Islam MW, et al. Neuropharmacological actions of Portulaca oleraceae L V. sativa (Hawk). J Ethnoph armacol. 2001;76:171-176
Rashed AN, Afifi FU, Disi AM. Simple evaluation of the wound healing activity of a crude extract of Portulaca oleracea L. (growing in Jordan) in Mus musculus JVI-1. J Ethnopharmacol. 2003;88: 131-136.
Oiu L, Howe P, Zhou Ye, Xuz, Hocart C, Zhang R. Fatty acids and β-carotene in Australian purslane (Portulaca oleracea) varieties. J Chromatogr A. 2000; 893:207–213.
Dkhil M, Abdel Moniem A, Al–Quraishy S, Saleh R. Antioxidant effect of purslane and its mechanism of action. J Med Plant Research. 2011;5:1589- 1563.
Al-Quraishy SA, Mohamed A, Dkhil AB, Ahmed E, Abdel Moneim BC. Protective effects of Portulaca oleracea against rotenone mediated depletion of glutathione in the striatum of rats as an animal model of Parkinson’s disease. Pesticide Biochemistry and Physiology. 2012;103:108-114.
El-Sayed MI. Effects of Portulaca oleracea L. seeds in treatment of type-2 diabetes mellitus patients as adjunctive and alternative therapy. J Ethnopharmacol. 2011;137:643-651.
Abdalla HM Jr. Purslane extract effects on obesity-induced diabetic rats fed a high-fat diet. Malays J Nutr. 2010;16:419-429.
Rajyalakshmi G, Reddy A, Rajesham VV. A comparative antihyperlipidemic activity of atorvastatin with simvastatin in rats. The Internet Journal of Pharmacology. 2009;6:2.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502.
Carletons HM, Drury RAB, Willington EA, Cameron R. Carleton's histological techniques. 5th ed. Oxford: Oxford University press;1980:140-222.
Bancroft, JD, Stevens A. Theory and practice of histological techniques. 2nd ed. Churchill: Livingestone;1982:374-375.
Liu JP, Tang Y, Zhou S, Toh BH, McLean C, Li H. Cholesterol involvement in the pathogenesis of neurodegenerative diseases. Mol Cell Neurosci. 2010;43:33–42.
Dietschy JM, Turley SD. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res. 2004;45: 8:1375–1397.
Pfrieger FW. Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci. 2003;60:1158–1171.
Marinis De, Martini C, Trentalance A, Pallottini V. Sex differences in hepatic regulation of cholesterol homeostasis. J Endocrinol. 2008;198:635-643.
Björkhem I, Lütjohann D, Diczfalusy U, Ståhle L, Ahlborg G, Wahren J. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res. 1998;39:1594–1600.
Björkhem I. Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med. 2006;260:493–508.
Vejux A, Malvitte L, Lizard G. Side effects of oxyysterol: cytotoxicity, oxidation, inflammation and phospholipidosis. Braz J Med Biol Res. 2008;41:545-556.
Soltan SSAM. The Effects of varieties sources of omega-3 fatty acids on diabetes in rats. Food and Nutrition Sciences. 2012;3:1404-1412.
Chen Y, Shen Z, Chen X. Evaluation of free radicals scavenging and immunity modulatory activities of purslane polysaccharides. J food Composit Anal. 2007;22:303-306.
Hayashi H, Campenot RB, Vance DE, Vance JE. Glial lipoproteins stimulate axon growth of central nervous system neurons in compartmented cultures. J Biol Chem. 2004;279:1409–1415.
Wahrie SE, Jiang H, Parsadanian M, et al. ABCA1 is required for normal central nervous system apoE levels and for lipidation of astrocyte-secreted apoE. J Biol Chem. 2004;279:40987–40993.
Hering H, Lin CC, Sheng M. Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability. J Neurosci. 2003;23:3262–3271.
Swanson RA, Ying W, Kauppinen TM. Astrocyte influences on ischemic neuronal death. Curr Mol Med. 2004;4:193-205.
Nedergaard M, Dirnagl U. Role of glial cells in cerebral ischemia. Glia. 2005;50:281-286.
Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119:7-35.
Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 2009;32:638-647.
Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest. 2002;110:597–603.
Cuzner ML, Davison AN, Gregson NA. Turnover of brain mitochondrial membrane lipids. Biochem J. 1966;101:618–626.
Russell DW, Halford RW, Ramirez DM, Shah R, Kotti T. Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain. Annu Rev Biochem. 2009;78: 1017-1040
Kirsch C, Eckert GP, Mueller WE. Statin effects on cholesterol micro-domains in brain plasma membranes. Biochem Pharmacol. 2003; 65:843–856.
Hohsfield LA, Daschil N, Orädd G, Strömberg I, Humpel C. Vascular pathology of 20-month-old hypercholesterolemia mice in comparison to triple-transgenic and APPSwDI Alzheimer's disease mouse models. Mol Cell Neurosci. 2014;63:83-95.
Franciosi S, Gama MA, Sosa D, et al. Novel cerebrovascular pathology in mice fed a high cholesterol diet. Mol Neurodegener. 2009;4:42.
Shimizu F, Kanda T. Disruption of blood –brain barrier in inflammatory neurological diseases. Brain Nerve. 2013;65:165-76.
Abbott NJ. Astrocyte-endothelial interactions and blood–brain barrier permeability. J Anat. 2002;200;629–638.
Wolburg H, Lippoldt A. Tight junctions of the blood–brain barrier: Development, composition and regulation. Vasc Pharmacol. 2002;38:323–337.
Plumb J, McQuaid S, Mirakhur M, Kirk J. Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis. Brain Pathol. 2002;12:154–169.
Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7:41–53.
Willis CL, Nolan CC, Reith SN, et al. Focal astrocyte loss is followed by microvascular damage, with subsequent repair of the blood–brain barrier in the apparent absence of direct astrocytic contact. Glia. 2004;45:325–337.
Ahmida MH. Evaluation of in vivo antioxidant and hepatoprotective activity of P. oleracea against paracetamol induced liver toxicity in male rats. American Journal of Pharmacology and Toxicology. 2010;5:167-176.
Moneim AEA, Nasr I, Dkhil MA, Quraishy S. Neuronal activities of P. oleracea in adult rats. Journal of Medicinal Plants Research. 2012;6:3162-3168.
Wang CQ, Yang GQ. Betacyanins from Portulaca oleracea L. ameliorate cognition deficits and attenuate oxidative damage induced by D-galactose in the brains of senescent mice. Phytomedicine. 2010;17:527-532.
Karimi G, Khoei A, Omidi A, et al. Protective effect of aqueous and ethanolic extracts of P. oleracea against cisplatin induced nephrotoxicity. Iranian Journal of Basic Medical Sciences. 2010;13:31-35.
Besong SA, Ezekwe MO, Ezekwe EI. Evaluating the effects of freeze-dried supplements of purslane (P. oleracea) on blood lipids in hypercholesterolemic adults. International Journal of Nutrition and Metabolism. 2011; 3:43–49.
Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E. Alzheimer's disease. Lancet. 2011;377:1019-1031.
Xue QS, Sparks DL, Streit WJ. Microglial activation in the hippocampus of hypercholesterolemic rabbits occurs independent of increased amyloid production. J Neuroinflammation. 2007;4:20.