Chinese yam extracts containing β-sitosterol and ethyl linoleate protect against atherosclerosis in apolipoprotein E-deficient mice and inhibit muscular expression of VCAM-1 in vitro.

Atherosclerosis is a chronic inflammatory disease, which is associated with increased expression of adhesion molecules and monocyte recruitment into the arterial wall. This study evaluated whether hexane extracts from the edible part (DB-H1) or bark region (DB-H2) of Dioscorea. batatas Decne have anti-atherosclerotic properties in vivo and in vitro experiments. We also identified bioactive components in the hexane extracts. Thirty-six apolipoprotein E (ApoE(-/-) ) mice and 12 control (C57BL/6J) mice were given a Western-type diet for 11 or 21 wk. To examine the effects of yam extracts on lesion development, ApoE(-/-) mice were orally administered DB-H1 or DB-H2 for the duration of the study (200 mg/kg b.w./day, 3 times per wk). Both DB-H1 and DB-H2 significantly reduced the total atherosclerotic lesion area in the aortic root. In addition, plasma concentrations of total cholesterol, oxidized-low-density lipoprotein, and c-reactive protein were decreased by administration of DB-H1 and DB-H2. Consistent with the in vivo observations, DB-H1 and DB-H2 inhibited tumor necrosis factor (TNF)-α-induced vascular cell adhesion molecule-1 expression and adhesion of THP-1 monocytes to TNF-α-activated vascular smooth muscle cells. It was also found that treatment with DB-H1 or DB-H2 resulted in the inhibition nitric oxide (NO) and reactive oxygen species production and iNOS expression in macrophages. Thus, DB-H1 and DB-H2 seem to influence atherosclerosis by affecting the production of inflammatory mediators in vivo. Our results suggest that yam extracts have the potential to be used in the prevention of atherosclerosis.

[1]  G. Assmann,et al.  FTY720, a Synthetic Sphingosine 1 Phosphate Analogue, Inhibits Development of Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice , 2007, Circulation.

[2]  Seong-Jun Cho,et al.  Induction of apoptosis and expression of apoptosis related genes in human epithelial carcinoma cells by Helicobacter pylori VacA toxin. , 2003, Toxicon : official journal of the International Society on Toxinology.

[3]  Nancy R Cook,et al.  Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. , 2002, The New England journal of medicine.

[4]  Eran Leitersdorf,et al.  Atherosclerosis in the apolipoprotein-E-deficient mouse: a decade of progress. , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[5]  K. Cheng,et al.  Decrease of plasma glucose by allantoin, an active principle of yam ( Dioscorea spp.), in streptozotocin-induced diabetic rats. , 2010, Journal of agricultural and food chemistry.

[6]  V. Puranik,et al.  A potential plasmid-curing agent, 8-epidiosbulbin E acetate, from Dioscorea bulbifera L. against multidrug-resistant bacteria. , 2008, International journal of antimicrobial agents.

[7]  Aldons J. Lusis,et al.  Atherosclerosis : Vascular biology , 2000 .

[8]  E. Tuzcu,et al.  Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease , 2005 .

[9]  R. Ross,et al.  ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[10]  M. Moghadasian,et al.  Comparison of Cholesterol-Lowering Efficacy and Anti-Atherogenic Properties of Hydrogenated versus Non-Hydrogenated (Phytrol™) Tall Oil-Derived Phytosterols in Apo E-Deficient Mice , 2003, Cardiovascular Drugs and Therapy.

[11]  A. Becker,et al.  Elevated plasma levels of oxidized low-density lipoprotein relate to the presence of angiographically detected complex and thrombotic coronary artery lesion morphology in patients with unstable angina. , 2007, Circulation journal : official journal of the Japanese Circulation Society.

[12]  R. Watson,et al.  Antioxidant activity of dioscorea and dehydroepiandrosterone (DHEA) in older humans. , 1996, Life sciences.

[13]  P. Ridker,et al.  Potential cost-effectiveness of C-reactive protein screening followed by targeted statin therapy for the primary prevention of cardiovascular disease among patients without overt hyperlipidemia. , 2003, The American journal of medicine.

[14]  S. Pyo,et al.  Inhibition of TNF-α-induced adhesion molecule expression by diosgenin in mouse vascular smooth muscle cells via downregulation of the MAPK, Akt and NF-κB signaling pathways. , 2010, Vascular pharmacology.

[15]  R. Virmani,et al.  Statin Treatment Is Not Associated With Consistent Alterations in Inflammatory Status of Carotid Atherosclerotic Plaques: A Retrospective Study in 378 Patients Undergoing Carotid Endarterectomy , 2006, Stroke.

[16]  Juei-Tang Cheng,et al.  Dioscorea as the principal herb of Die-Huang-Wan, a widely used herbal mixture in China, for improvement of insulin resistance in fructose-rich chow-fed rats. , 2007, Journal of ethnopharmacology.

[17]  Jean-Fred Fontaine,et al.  CXCL5 limits macrophage foam cell formation in atherosclerosis. , 2013, The Journal of clinical investigation.

[18]  S. Blankenberg,et al.  Adhesion molecules and atherosclerosis. , 2003, Atherosclerosis.

[19]  Masanori Arita,et al.  Databases on food phytochemicals and their health-promoting effects. , 2011, Journal of agricultural and food chemistry.

[20]  Keisuke Matsuoka,et al.  Study of thermodynamic parameters for solubilization of plant sterol and stanol in bile salt micelles. , 2008, Chemistry and physics of lipids.

[21]  O. Wagner,et al.  Effect of fatty acids on expression of endothelial leukocyte adhesion molecules , 2003 .

[22]  M. Cybulsky,et al.  Adhesion of Monocytes to Arterial Endothelium and Initiation of Atherosclerosis Are Critically Dependent on Vascular Cell Adhesion Molecule-1 Gene Dosage , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[23]  C. Mori,et al.  Transient Increase in Plasma Oxidized LDL During the Progression of Atherosclerosis in Apolipoprotein E Knockout Mice , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[24]  Chuan-Hsiao Han,et al.  Antioxidant activities of dioscorin, the storage protein of yam (Dioscorea batatas Decne) tuber. , 2001, Journal of agricultural and food chemistry.

[25]  B. Yeganeh,et al.  Antiatherogenic effects of dietary plant sterols are associated with inhibition of proinflammatory cytokine production in Apo E-KO mice. , 2005, The Journal of nutrition.

[26]  K. Ley,et al.  Adhesion molecules and atherogenesis. , 2001, Acta physiologica Scandinavica.

[27]  O. Kwon,et al.  Culinary plants and their potential impact on metabolic overload , 2011, Annals of the New York Academy of Sciences.

[28]  J. Breslow Mouse Models of Atherosclerosis , 1996, Science.

[29]  K. Moore,et al.  Macrophages in the Pathogenesis of Atherosclerosis , 2011, Cell.

[30]  Mark B Pepys,et al.  C-reactive protein: a critical update. , 2003, The Journal of clinical investigation.

[31]  Michiko Ito,et al.  Dietary fatty acid ethyl esters and lecithin-cholesterol acyltransferase activity in rats , 1993 .

[32]  S. Pyo,et al.  Suppression of adhesion molecule expression by phenanthrene-containing extract of bulbils of Chinese Yam in vascular smooth muscle cells through inhibition of MAPK, Akt and NF-κB. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.