The Effect of Hydroalcoholic Extract of Dorema Aucheri on CD40 Protein Expression in Thoracic Aorta of Male White Rabbits Fed with Hypercholesterolemic Diet

Document Type : Original Article (s)

Authors

1 Associate Professor, Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Anatomical Sciences, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran

3 Perofessor, Department of Pharmacognosy, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

4 Assistant Professor, Department of Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Coronary artery disease (CAD) is caused by the accumulation of fatty streaks in the intima of vessels leading to atherosclerosis. Nowadays, medicinal herbs are attracting much attention in this field. Hence, the aim of the present research was to compare the effects of hydroalcoholic extract of the Dorema Aucheri and statins on CD40 protein expression.Methods: Thirty white male rabbits (1250-1500 grams) were purchased from the Pasteur Institute of Tehran. The animals were housed in clean metal hutches and acclimatized on rabbit chow for two weeks prior to the commencement of the experiment. The animals were subsequently randomly divided into five groups, each containing six rabbits. The feeding experiment was conducted at room temperature of 28˚C. After two weeks, four groups of rabbits were fed with a diet containing 1% cholesterol (hypercholesterolemic diet), hypercholesterolemic diet plus 6 mg/kg lovastatin, hypercholesterolemic diet plus 200 mg Dorema Aucheri extract, and hypercholesterolemic diet plus 400 mg Dorema Aucheri extract for 45 days. The fifth group only received a normal diet without cholesterol.Findings: Different levels of staining were observed in the 30 sections taken from the thoracic aorta of the rabbits. However, the two groups that received the extract were not significantly different. The staining was completely inconsiderable in the control. Conclusion: Dorema Aucheri extract had a significant effect on decreasing CD40 proteins formation. This property might be due to the presence of flavonoids, antioxidants and other compounds such as furanocoumarins that have been identified in the plant extract.

Keywords


  1. American Heart Association (AHA): Heart disease, diet and nutrition [Online]. 2006; Available from: URL: http://www.heart.Orgl-presenter.org/.
  2. American Heart association (AHA): Primary prevention [Online]. 2006; Available from: URL: http://www.heart.Orgl-presenter.org/.
  3. American Dietetic Association (ADA).analysis library on hyperlipidemia [Online]. 2006; Available From: URL: http://www.eat right.org/.
  4. Athyros VG, Ganotakis ES, Elisaf MS, Liberopoulos EN, Goudevenos IA, Karagiannis A. Prevalence of vascular disease in metabolic syndrome using three proposed definitions. Int J Cardiol 2007; 117(2): 204-10.
  5. Aygun AD, Gungor S, Ustundag B, Gurgoze MK, Sen Y. Proinflammatory cytokines and leptin are increased in serum of prepubertal obese children. Mediators Inflamm 2005; 2005(3): 180-3.
  6. Badimon L, Martinez-Gonzalez J, Llorente-Cortes V, Rodriguez C, Padro T. Cell biology and lipoproteins in atherosclerosis. Curr Mol Med 2006; 6(5): 439-56.
  7. Barter PJ, Rye KA. The rationale for using apoA-I as a clinical marker of cardiovascular risk. J Intern Med 2006; 259(5): 447-54.
  8. Bartolucci AA, Howard G. Meta-analysis of data from the six primary prevention trials of cardiovascular events using aspirin. Am J Cardiol 2006; 98(6): 746-50.
  9. Basu A, Devaraj S, Jialal I. Dietary factors that promote or retard inflammation. Arterioscler Thromb Vasc Biol 2006; 26(5): 995-1001.
  10. Lin R, Liu J, Gan W, Yang G. C-reactive protein-induced expression of CD40-CD40L and the effect of lovastatin and fenofibrate on it in human vascular endothelial cells. Biol Pharm Bull 2004; 27(10): 1537-43.
  11. Armitage RJ, Fanslow WC, Strockbine L, Sato TA, Clifford KN, Macduff BM, et al. Molecular and biological characterization of a murine ligand for CD40. Nature 1992; 357(6373): 80-2.
  12. Schonbeck U, Libby P. CD40 signaling and plaque instability. Circ Res 2001; 89(12): 1092-103.
  13. Li D, Liu L, Chen H, Sawamura T, Mehta JL LOX-1, an oxidized LDL endothelial receptor, induces CD40/CD40L signaling in human coronary artery endothelial cells. Arterioscler Thromb Vasc Biol 2003; 23(5): 816-21.
  14. Zargari A. Pharmaceutical plants. Tehran: Tehran University Press; 1997. p. 212-21. [In Persian].
  15. Ghahraman A. Iran choromophites, Umbrella plants. Tehran: Tehran university center publisher; 1999. p. 682-684. [In Persian]
  16. Wollenweber E, Dörr M, Rustiyan A. Dorema aucheri, the first umbelliferous plant found to produce exudate flavonoids. Phytochemistry 1995; 38(6): 1417-27.
  17. Hsiao G, Shen MY, Lin KH, Lan MH, Wu LY, Chou DS, et al. Antioxidative and hepatoprotective effects of Antrodia camphorata extract. J Agric Food Chem 2003; 51(11): 3302-8.
  18. Sajadi E, Jafari A. Collection, Idendificate and primary phytochemical assessment of selected plants from eastern Dena Mountain. Isfahan: Isfahan University of Medical Sciences; 2007. p. 90. [In Persian].
  19. Syed M, Khalid MR, Chaudhary FM, Bhatty MK. Antibacterial activity of Umbelliferae. Carum carvi, Petroselinum crispum and Dorema ammoniacum oils. PJSIR 1987; 30: 106-10.
  20. Rajani M, Saxena N, Ravishankara MN, Desai N, Padh H. Evaluation of the Antimicrobial Activity of Ammoniacum Gum from Dorema ammoniacum. Pharmaceutical Biology 2002; 40(7): 534-41.
  21. Afshari-poor S. Treitz & evans pharmacognosy. Isfahan: Medical university of Isfahan; 2007. p. 115-240. [In Persian].
  22. Ceska O, Chaudhary SK, Warrington PJ, Ashwood-Smith MJ. Photoactive furocoumarins in fruits of some umbellifers. Phytochemistry 1986; 26(1): 165-9.
  23. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344(8934): 1383-9.
  24. Sukhova GK, Williams JK, Libby P. Statins reduce inflammation in atheroma of nonhuman primates independent of effects on serum cholesterol. Arterioscler Thromb Vasc Biol 2002; 22(9): 1452-8.
  25. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary Prevention of Acute Coronary Events With Lovastatin in Men and Women With Average Cholesterol Levels. JAMA 1998; 279(20): 1615-22.
  26. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nature Medicine 2000; 6: 1399-402.
  27. Chang WC, Yu YM, Hsu YM, Wu CH, Yin PL, Chiang SY, et al. Inhibitory effect of Magnolia officinalis and lovastatin on aortic oxidative stress and apoptosis in hyperlipidemic rabbits. J Cardiovasc Pharmacol 2006; 47(3): 463-8.
  28. Zhu BQ, Sun YP, Sievers RE, Isenberg WM, Moorehead TJ, Parmley WW. Effects of etidronate and lovastatin on the regression of atherosclerosis in cholesterol-fed rabbits. Cardiology 1994; 85(6): 370-7.
  29. Samsam Shariat SH. Extraction of the Effective Material in Plants and Route to Evaluate them. [Thesis]. Isfahan: Isfahan University of Medical Sciences; 1992: p. 15-6. [In Persian].
  30. Hakkinen T, Karkola K, Yla-Herttuala S. Macrophages, smooth muscle cells, endothelial cells, and T-cells express CD40 and CD40L in fatty streaks and more advanced human atherosclerotic lesions. Colocalization with epitopes of oxidized low-density lipoprotein, scavenger receptor, and CD16 (Fc gammaRIII). Virchows Arch 2000; 437(4): 396-405.
  31. Schonbeck U, Mach F, Libby P. CD154 (CD40 ligand). Int J Biochem Cell Biol 2000; 32(7): 687-93.
  32. Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 1998; 394(6689): 200-3.
  33. Robertson AK, Hansson GK. T cells in atherogenesis: for better or for worse? Arterioscler Thromb Vasc Biol 2006; 26(11): 2421-32.
  34. Mach F, Schonbeck U, Sukhova GK, Bourcier T, Bonnefoy JY, Pober JS, et al. Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for CD40-CD40 ligand signaling in atherosclerosis. Proc Natl Acad Sci USA 1997; 94(5): 1931-6.
  35. Wagner AH, Guldenzoph B, Lienenluke B, Hecker M. CD154/CD40-mediated expression of CD154 in endothelial cells: consequences for endothelial cell-monocyte interaction. Arterioscler Thromb Vasc Biol 2004; 24(4): 715-20.
  36. Schonbeck U, Gerdes N, Varo N, Reynolds RS, Horton DB, Bavendiek U, et al. Oxidized low-density lipoprotein augments and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors limit CD40 and CD40L expression in human vascular cells. Circulation 2002; 106(23): 2888-93.
  37. Laman JD, de Smet BJ, Schoneveld A, van MM. CD40-CD40L interactions in atherosclerosis. Immunol Today 1997; 18(6): 272-7.
  38. Ylä-Herttuala S. Is oxidized low-density lipoprotein present in vivo? Current Opinion in Lipidology 1998; 9(4): 337-44.
  39. Mulhaupt F, Matter CM, Kwak BR, Pelli G, Veillard NR, Burger F, et al. Statins (HMG-CoA reductase inhibitors) reduce CD40 expression in human vascular cells. Cardiovasc Res 2003; 59(3): 755-66.
  40. Diomede L, Albani D, Sottocorno M, Donati MB, Bianchi M, Fruscella P, et al. In vivo anti-inflammatory effect of statins is mediated by nonsterol mevalonate products. Arterioscler Thromb Vasc Biol 2001; 21(8): 1327-32.
  41. Yazdanpanah K. Effects of dill juice on serum low density lipoprotein, triglyceride and high density lipoprotein in patients with hyperlipidemia. Scientific Journal of Kurdistan University of Medical Sciences 2001; 5(3): 1-4. [In Persian].
  42. Sadeghi H, Mirzaee A, Delaviz H. Antihyperlipidaemic and antihypercholesterol-aemic effects of Dorema aucheri. Iranian Journal of Pharmaceutical Research 2004; 3(1): 59. [In Persian].