Aged Garlic Extract and One of the Constituent, (+)-(2S,3R)-Dehydrodiconiferyl Alcohol, Inhibits Alkaline Phosphatase Activity Induced by Inflammation Factors in Human Vascular Smooth Muscle Cells

DOI: 10.4236/fns.2014.52023   PDF   HTML   XML   4,118 Downloads   5,506 Views   Citations


Previous clinical study showed that aged garlic extract (AGE) has a preventive effect of vascular calcification in patients with coronary artery diseases. It has been reported that vascular smooth muscle cells (VSMC) and inflammatory cells including macrophages and lymphocytes migrate to sub-intimal region where atherosclerotic plaques are formed, and VSMC can differentiate into osteoblast-like cells, which are represented by the induction of alkaline phosphatase (ALP). We found that primary human coronary artery smooth muscle cells (HCASMC) showed the increased ALP activity, when cultured in the medium containing ascorbic acid, β-glycerophosphate, dexamethasone (IM), and supplemented with conditioned medium from macrophages (MCM). Then we tested the effect of AGE subdivided fractions and several compounds found in AGE, and then found that ((+)-(2S,3R)-Dehydrodiconiferyl alcohol, a dilignol compound existed in hydrophobic fraction of AGE, inhibited ALP activity in HCASMC.

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T. Yamakawa, T. Matsutomo, T. Hofmann and Y. Kodera, "Aged Garlic Extract and One of the Constituent, (+)-(2S,3R)-Dehydrodiconiferyl Alcohol, Inhibits Alkaline Phosphatase Activity Induced by Inflammation Factors in Human Vascular Smooth Muscle Cells," Food and Nutrition Sciences, Vol. 5 No. 2, 2014, pp. 177-184. doi: 10.4236/fns.2014.52023.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. Detrano, A. D. Guerci, J. J. Carr, D. E. Bild, G. Burke, A. R. Folsom, K. Liu, S. Shea, M. Szklo, D. A. Bluemke, D. H. O’Leary, R. Tracy, K. Watson, N. D. Wong and R. A. Kronmal, “Coronary Calcium as a Predictor of Coronary Events in Four Racial or Ethnic Groups,” The New England Journal of Medicine, Vol. 358, No. 13, 2008, pp. 1336-1345.
[2] R. Wayhs, A. Zelinger and P. Raggi, “High Coronary Artery Calcium Scores Pose an Extremely Elevated Risk for Hard Events,” The Journal of the American College of Cardiology, Vol. 39, No. 2, 2002, pp. 225-230.
[3] T. Ikeda, T. Shirasawa, Y. Esaki, S. Yoshiki and K. Hirokawa, “Osteopontin mRNA Is Expressed by Smooth Muscle-Derived Foam Cells in Human Atherosclerotic Lesions of the Aorta,” The Journal of Clinical Investigation, Vol. 92, No. 6, 1993, pp. 2814-2820.
[4] C. M. Shanahan, N. R. Cary, J. C. Metcalfe and P. L. Weissberg, “High Expression of Genes for CalcificationRegulating Proteins in Human Atherosclerotic Plaques,” Journal of Clinical Investigation, Vol. 93, 1994, pp. 23932402.
[5] C. R. Dhore, J. P. Cleutjens, E. Lutgens, K. B. Cleutjens, P. P. Geusens, P. J. Kitslaar, J. H. Tordoir, H. M. Spronk, C. Vermeer and M. J. Daemen, “Differential Expression of Bone Matrix Regulatory Proteins in Human Atherosclerotic Plaques,” Arteriosclerosis, Thrombosis and Vascular Biology, Vol. 21, No. 12, 2001, pp. 1998-2003.
[6] M. A. Engelse, J. M. Neele, A. L. Bronckers, H. Pannekoek and C. J. de Vries, “Vascular Calcification: Expression Patterns of the Osteoblast-Specific Gene Core Binding Factor Alpha-1 and the Protective Factor Matrix Gla Protein in Human Atherogenesis,” Cardiovascular Research, Vol. 52, No. 2, 2001, pp. 281-289.
[7] K. L. Tyson, J. L. Reynolds, R. McNair, Q. Zhang, P. L. Weissberg and C. M. Shanahan, “Osteo/Chondrocytic Transcription Factors and Their Target Genes Exhibit Distinct Patterns of Expression in Human Arterial Calcification,” Arteriosclerosis, Thrombosis and Vascular Biology, Vol. 23, No. 3, 2003, pp. 489-494.
[8] K. Bostrom, K. E. Watson, S. Horn, C. Wortham, I. M. Herman and L. L. Demer, “Bone Morphogenetic Protein Expression in Human Atherosclerotic Lesions,” The Journal of Clinical Investigation, Vol. 91, No. 4, 1993, pp. 1800-1809.
[9] L. Jonasson, J. Holm, O. Skalli, G. Bondjers and G. K. Hansson, “Regional Accumulations of T Cells, Macrophages, and Smooth Muscle Cells in the Human Atherosclerotic Plaque,” Arteriosclerosis, Thrombosis and Vascular Biology, Vol. 6, 1986, pp. 131-138.
[10] H. C. Stary, “Lipid and Macrophage Accumulations in Arteries of Children and the Development of Atherosclerosis,” The American Journal of Clinical Nutrition, Vol. 72, No. 5, 2000, pp. 1297S-1306S.
[11] M. Y. Speer, H. Y. Yang, T. Brabb, E. Leaf, A. Look, W. L. Lin, A. Frutkin, D. Dichek and C. M. Giachelli, “Smooth Muscle Cells Give Rise to Osteochondrogenic Precursors and Chondrocytes in Calcifying Arteries,” Circulation Research, Vol. 104, No. 6, 2009, pp. 733-741.
[12] A. Kizu, A. Shioi, S. Jono, H. Koyama, Y. Okuno and Y. Nishizawa, “Statins Inhibit in Vitro Calcification of Human Vascular Smooth Muscle Cells Induced by Inflammatory Mediators,” Journal of Cellular Biochemisty, Vol. 93, No. 5, 2004, pp. 1011-1019.
[13] A. Shioi, M. Katagi, Y. Okuno, K. Mori, S. Jono, H. Koyama and Y. Nishizawa, “Induction of Bone-Type Alkaline Phosphatase in Human Vascular Smooth Muscle Cells: Roles of Tumor Necrosis Factor-Alpha and Oncostatin M Derived from Macrophages,” Circulation Research, Vol. 91, No. 1, 2002, pp. 9-16.
[14] H. Amagase, B. L. Petesch, H. Matsuura, S. Kasuga and Y. Itakura, “Intake of Garlic and Its Bioactive Components,” Journal of Nutrition, Vol. 131, No. 3, 2001, pp. 955S-962S.
[15] M. Steiner, A. H. Khan, D. Holbert and R. I. Lin, “A Double-Blind Crossover Study in Moderately Hypercholesterolemic Men that Compared the Effect of Aged Garlic Extract and Placebo Administration on Blood Lipids,” American Journal of Clinical Nutrition, Vol. 64, No. 6, 1996, pp. 866-870.
[16] K. Rahman and D. Billington, “Dietary Supplementation with aged Garlic Extract Inhibits ADP-Induced Platelet Aggregation in Humans,” Journal of Nutrition, Vol. 130, No. 1, 2000, pp. 2662-2665.
[17] M. Steiner and W. Li, “Aged Garlic Extract, a Modulator of Cardiovascular Risk Factors: A Dose-Finding Study on the Effects of AGE on Platelet Functions,” Journal of Nutrition, Vol. 131, No. 3S, 2001, pp. 980S-984S.
[18] B. H. Lau, “Suppression of LDL Oxidation by Garlic,” Journal of Nutrition, Vol. 131, No. 3S, 2001, pp 985S988S.
[19] M. J. Budoff, “Aged Garlic Extract Retards Progression of Coronary Artery Calcification,” Journal of Nutrition, Vol. 136, No. 3S, 2006, pp. 741S-744S.
[20] M. J. Budoff, J. Takasu, F. R. Flores, Y. Niihara, B. Lu, B. H. Lau, R. T. Rosen and H. Amagase, “Inhibiting Progression of Coronary Calcification Using Aged Garlic Extract in Patients Receiving Statin Therapy: A Preliminary Study,” Preventive Medicine, Vol. 39, No. 5, 2004, pp. 985-991.
[21] H. Sowa, H. Kaji, L. Canaff, G. N. Hendy, T. Tsukamoto, T. Yamaguchi, K. Miyazono, T. Sugimoto and K. Chihara, “Inactivation of Menin, The Product of the Multiple Endocrine Neoplasia Type 1 Gene, Inhibits the Commitment of Multipotential Mesenchymal Stem Cells into the Osteoblast lineage,” The Journal of Biological Chemistry, Vol. 278, No. 23, 2003, pp. 21058-21069.
[22] A. Shioi, Y. Nishizawa, S. Jono, H. Koyama, M. Hosoi and H. Morii, “Beta-Glycerophosphate Accelerates Calcification in Cultured Bovine Vascular Smooth Muscle Cells,” Arteriosclerosis, Thrombosis and Vascular Biology, Vol. 15, No. 11, 1995, pp. 2003-2009.
[23] N. Morihara, M. Hayama and H. Fujii, “Aged Garlic Extract Scavenges Superoxide Radicals,” Plant Foods for Human Nutrition, Vol. 66, No. 1, 2011, pp. 17-21.
[24] T. Matsutomo, T. D. Stark and T. Hofmann, “In Vitro Activity-Guided Identification of Antioxidants in Aged Garlic Extract,” Journal Agricultural and Food Chemistry, Vol. 61, No. 12, 2013, pp. 3059-3067.
[25] L. C. Hofbauer, J. Schrader, U. Niebergall, V. Viereck, A. Burchert, D. Horsch, K. T. Preissner and M. Schoppet, “Interleukin-4 Differentially Regulates Osteoprotegerin Expression and Induces Calcification in Vascular Smooth Muscle Cells,” Thrombosis and Haemostasis, Vol. 95, No. 4, 2006, pp. 708-714.
[26] A. Van Campenhout, C. S. Moran, A. Parr, P. Clancy, C. Rush, H. Jakubowski and J. Golledge, “Role of Homocysteine in Aortic Calcification and Osteogenic Cell Differentiation,” Atherosclerosis, Vol. 202, No. 2, 2009, pp. 557-566.
[27] C. Goettscha, C. Hamannb, U. Hempelc, M. Raunera and L. Hofbauera, “Oxidized Lipids Induce Vascular Calcification through the Nfat and Stat3 Pathway,” Bone, Vol. 44, Suppl. 2, 2009, pp. S297-S298.
[28] M. Melino, V. L. Gadd, G. V. Walker, R. Skoien, H. D. Barrie, D. Jothimani, L. Horsfall, A. Jones, M. J. Sweet, G. P. Thomas, A. D. Clouston, J. R. Jonsson and E. E. Powell, “Macrophage Secretory Products Induce an Inflammatory Phenotype in Hepatocytes,” World Journal of Gastroenterology, Vol. 18, No. 15, 2012, pp. 1732-1744.
[29] I. J. Lorch, “Alkaline Phosphatase and the Mechanism of Ossification,” The Journal of Bone and Joint Surgery, Vol. 31B, No. 1, 1949, pp. 94-99.
[30] H. C. Stary, “Lipid and Macrophage Accumulations in Arteries of Children and the Development of Atheroscleosis,” American Journal of Clinical Nutrition, Vol. 72, No. 5, 2000, pp. 1297S-1306S.
[31] M. Jeziorska, C. McCollum and D. E. Woolley, “Calcification in Artherosclerotic Plaque of Human Carotid Artreies: Associations with Mast Cells and Macrophages,” The Journal of Pathology, Vol. 185, No. 1, 1998, pp. 1017.<10::AID-PATH71>3.0.CO;2-0
[32] Y. Tintut, J. Patel, M. Territo, T. Saini, F. Parhami and L. L. Demer, “Monocyte/Macrophage Regulation of Vascular Calcification in Vitro,” Circulation, Vol. 105, No. 5, 2002, pp. 650-655.
[33] G. G. Duthie, S. J. Duhie and J. A. M. Kyle, “Plant Polyphenols in Cancer and Heart Disease: Implications as Nutritional Antioxidants,” Nutrition Research Reviews, Vol. 13, No. 1, 2000 pp. 79-105.
[34] M. R. Negrao, E. Keating, A. Faria, I. Azevedo and M. J. Martins, “Acute Effect of Tea, Wine, Beer and Polyphenols on Ecto-Alkaline Phosphatase Activity in Human Vascular Smooth Muscle Cells,” Journal of Agricultural and Food Chemistry, Vol. 54, No. 12, 2006, pp. 49824988.
[35] Z. Dai, Y. Li, L. D. Quarles, T. Song, W. Pan, H. Zhou and Z. Xiao, “Resveratrol Enhances Proliferation and Osteoblastic Differentiation in Human Mesenchymal Stem Cells via ER-Dependent ERK1/2 Activation,” Phytomedicine, Vol. 14, No. 12, 2007, pp. 806-814.
[36] H. M. Jeong, E. H. Han, Y. H. Jin, Y. H. Choi, K. Y. Lee and H. G. Jeong, “Xanthohumol from the Hop Plant Stimulates Osteoblast Differentiation by RUNX2 Activation,” Biochemical and Biophysical Research Communications, Vol. 409, No. 1, 2011, pp. 82-89.

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