Browse > Article

Inhibitory Effect of Combination with Korean Red Gnseng and Morus Alba in High Fructose-induced Vascular Inflammation and Steatohepatitis  

Lee, Yun Jung (College of Oriental Medicine, Wonkwang University)
Yoon, Jung Joo (College of Oriental Medicine, Wonkwang University)
Lee, So Min (College of Oriental Medicine, Wonkwang University)
Kho, Min Chul (College of Oriental Medicine, Wonkwang University)
Kim, Hye Yoom (College of Oriental Medicine, Wonkwang University)
Ahn, You Mee (College of Oriental Medicine, Wonkwang University)
Kho, Joung Hyun (College of Oriental Medicine, Wonkwang University)
Lee, Kee Byoung (College of Oriental Medicine, Sangji University)
Lee, Ho Sub (College of Oriental Medicine, Wonkwang University)
Choi, Kyung Min (Institute of JinAn Red Ginseng Korea)
Kwon, Tae Oh (College of Life Science and Natural Resources, Wonkwang University)
Kang, Dae Gill (College of Oriental Medicine, Wonkwang University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.26, no.5, 2012 , pp. 724-731 More about this Journal
Abstract
This study was designed to elucidate whether combination with Korean red ginseng and Morus alba L. (MPM), traditional treatment for diabetes, ameliorates on high fructose-induced steatohepatitis and vascular inflammation. Animals were divided into four groups; Control receiving tap water, fructose-fed, rosiglitazone-treated fructose-fed rats, and MPM-treated fructose-fed rats both receiving supplemented with 60% fructose (n=10). The MPM or rosiglitazone groups initially received a high-fructose diet alone for 8 weeks, with supplementation with MPM or rosiglitazone, peroxisome proliferators-activated receptor gamma ($PPAR{\gamma}$) agonist, occurring during the final 6 weeks. Treatment with MPM significantly prevented the increase in c-reactive protein (CRP) levels in the high fructose group. MPM suppressed high fructose diet-induced vascular inflammation marker expression such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. MPM also reduced intima/media thickness of thoracic aorta. Histologic observation and oil red O staining demonstrated hepatic tissue damage and lipid accumulation were severe in high fructose group. Treatment with MPM ameliorated hepatic tissue morphology with minimized steatosis. In addition, MPM attenuated hepatitis by inhibition of monocyte chemoattractant protein-1 (MCP-1) expression. MPM-fed group showed lower serum GOT and GPT levels comparing with high fructose group. MPM and rosiglitazone (positive control) significantly decreased the size of epididymal adipocytes. Taken together, the administration of MPM inhibited high fructose-induced steatohepatitis and vascular inflammation. These results suggested that MPM is useful in the prevention or treatment of metabolic syndrome-related disorders such as fatty acid metabolism and vascular homeostasis.
Keywords
korean red ginseng; morus alba; metabolic syndrome; steatohepatitis; vascular inflammation;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Fortez, M., Ancellin, N., Andreelli, F., Saintillan, Y., Grondin, P., Kahn, A., Thorens, B., Vaulont, S., Viollet, B. Short-term overexpression of a constitutively active form of AMPK-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes. 54: 1331-1339, 2005.   DOI   ScienceOn
2 Nielsen, S., Guo, Z., Johnson, C.M., Hensrud, D.D., Jensen, M.D. Splanchnic lipolysis in human obesity. J. Clin. Invest. 113: 1582-1588, 2004.   DOI
3 Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 114: 1752-1761, 2004.   DOI
4 Kwon, K.R., Park, W.P., Kang, W.M., Jeon, E.Y., Jang, J.H. Identification and analysis of differentially expressed genes in mountain cultivated ginseng and mountain wild ginseng. J. Acupunct. Meridian. Stud. 4: 123-128, 2011.   DOI   ScienceOn
5 Liu, C.X., Xiao, P.G. Recent advances on ginseng research in China. J. Ethnopharmacol. 36: 27-38, 1992.   DOI   ScienceOn
6 Kitts, D., Hu, C. Efficacy and safety of ginseng. Public. Health. Nutr. 3: 473-485, 2000.
7 Enkhmaa, B., Shiwaku, K., Katsube, T., Kitajima, K., Anuurad, E., Yamasaki, M., Yamane, Y. Mulberry (Morus alba L.) leaves and their major flavonol quercetin 3-(6-malonylglucoside) attenuate atherosclerotic lesion development in LDL receptor-deficient mice. J. Nutr. 135: 729-734, 2005.   DOI
8 Miyahara, C., Miyazawa, M., Satoh, S., Sakai, A., Mizusaki, S. Inhibitory effects of mulberry leaf extract on postprandial hyperglycemia in normal rats. J. Nutr. Sci. Vitaminol. 50: 161-164, 2004.   DOI   ScienceOn
9 Lee, Y.J., Choi, D.H., Kim, E.J., Kim, H.Y., Kwon, T.O., Kang, D.G., Lee, H.S. Hypotensive, hypolipidemic, and vascular protective effects of Morus alba L. in rats fed an atherogenic diet. Am. J. Chin. Med. 39: 39-52, 2011.   DOI   ScienceOn
10 Park, S.H., Jeon, W.K., Kim, S.H., Kim, H.J., Park, D.I., Cho, Y.K., Sung, I.K., Sohn, C.I., Keum, D.K., Kim, B.I. Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults. J. Gastroenterol. Hepatol. 21: 138-143, 2006.   DOI   ScienceOn
11 Elliott, S.S., Keim, N.L., Stern, J.S., Teff, K., Havel, P.J. Fructose, weight gain, and the insulin resistance syndrome. Am. J. Clin. Nutr. 76: 911-922, 2002.   DOI
12 Hwang, I.S., Ho, H., Hoffman, B.B., Reaven, G.M. Fructose-induced insulin resistance and hypertension in rats. Hypertension. 10: 512-516, 1987.   DOI
13 Sanchez-Lozada, L.G., Tapia, E., Jimenez, A., Bautista, P., Cristobal, M., Nepomuceno, T., Soto, V., Avila-Casado, C., Nakagawa, T., Johnson, R.J, Herrera-Acosta, J., Franco, M. Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats. Am. J. Physiol. Renal. Physiol. 292: 423-429, 2007.
14 Feingold, K.R., Grunfeld, C. Role of cytokines in inducing hyperlipidemia. Diabetes. 41: 97-101, 1992.   DOI
15 Stenvinkel, P., Heimburger, O., Jogestrand, T. Elevated interleukin-6 predicts progressive carotid artery atherosclerosis in dialysis patients: Association with Chlamydia pneumoniae seropositivity. Am. J. Kidney. Dis. 39: 274-282, 2002.   DOI   ScienceOn
16 Duprez, D.A., Somasundaram, P.E., Sigurdsson, G., Hoke, L., Florea, N., Cohn, J.N. Relationship between Creactive protein and arterial stiffness in an asymptomatic population. J. Hum. Hypertens. 19: 515-519, 2005.   DOI   ScienceOn
17 Yoon, K.H., Lee, J.H., Kim, J.W., Cho, J.H., Choi, Y.H., Ko, S.H., Zimmet, P., Son, H.Y. Epidemic obesity and type 2 diabetes in Asia. Lancet. 11: 1681-1688, 2006.
18 Hommels, M.J, van der Ven A.J.A.M., Kroon, A.A., Kessels, A.G.H., Van Dieijen-Visser, M.P., Van Engelshoven, J.A.M., Bruggeman, C.A., De Leeuw, P.W. C-reactive protein, atherosclerosis and kidney function in hypertensive patients. J. Hum. Hypertens. 19: 521-526, 2005.   DOI   ScienceOn
19 Georg, P., Ludvik, B. Lipids and diabetes. J. Clin. Basic. Cardiol. 3: 159-162, 2000.
20 International Diabetes Federation. Diabetes Atlas, 2nd ed, 2003 Available at: www.eatlas.idf.org (accessed on July 12, 2008).
21 Tay, S.S., Mc Cormack, A., Rose, M.L. Effect of cognate human CD4+ Tcell and endothelial cell interactions upon chemokine production. Transplantatio.n 78(7):987-994, 2004.   DOI   ScienceOn
22 Uze, G., Pachman, L.M. Cytokines in juvenile dermatomyositis pathophysiology: potential and challenge. Curr. Opin. Rheumatol. 15(6):691-697, 2003.   DOI   ScienceOn
23 Frostegard, J., Wu, R., Haegerstrand, A., patarroyo, M., Lefver,, A.K. Mononuclear leukocytes exposed to oxidized low density lipoprotein secrete a factor that stimulates endothelial cells to express adhesion molecules. Atherosclerosis. 103: 213-219, 1993.   DOI   ScienceOn
24 Mes, Bouhle., M.A., Staels, B., Chinetti-Gbaguid, G. Peroxisome proliferator-activated receptors-from active regulators of macrophage biology to pharmacological targets in the treatment of cardiovascular disease. J. Intern. Med. 263(1):28-42, 2008.
25 Li, J.J., Zhu, C.G., Yu, B., Liu, Y.X., Yu, M.Y. The role of inflammation in coronary artery calcification. Agening. Res. Rev. 6(4):263-270, 2007.   DOI   ScienceOn
26 Jun, D.W. Non-alcoholic fatty liver disease. Korean J. Hepatol. 17: S332-S336, 2011.
27 Matteoni, C.A., Younossi, Z.M., Gramlich, T., Boparai, N., Liu, Y.C., Mc, Cullough, A.J. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 116: 1413-1419, 1999.   DOI   ScienceOn
28 Bugianesi, E., Leone, N., Vanni, E., Marchesini, G., Brunello, F., Rizzetto, M. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 123: 134-140, 2002.   DOI   ScienceOn
29 Marrero, J.A., Fontana, R.J., Su, G.L., Conjeevaram, H.S., Emick, D.M., Lok, A.S. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology. 36: 1349-1354, 2002.   DOI
30 Marchesini, G., Bugianesi, E., Forlani, G., Cerrelli, F., Lenzi, M., Manini, R., Natale, S., Vanni, E., Villanova, N., Melchionda, N., Rizzetto, M. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 37: 917-923, 2003.   DOI   ScienceOn
31 Hong, M.H., Lim, H.K., Park, J.E., Jun, N.J., Lee, Y.J., Cho, M.J., Kim, S.M. The Antihypertensive and Vasodilating Effects of Adventitious Root Extracts of Wild Ginseng. J. Korean. Soc. Appl. Biol. Chem. 51: 102-107, 2008.   DOI   ScienceOn
32 Mizuno, M., Yamada, J., Terai, H., Kozukue, N., Lee, Y.S., Tsuchide, H. Differences in immunomodulating effects between wild and cultured Panax ginseng. Biochem. Biophys. Res. Commun. 200: 1672-1678, 1994.   DOI   ScienceOn
33 Neuschwander-Tetri, B.A., Brunt, E.M., Wehmeier, K.R., Oliver, D., Bacon, B.R. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology. 38: 1008-1017, 2003.   DOI
34 Quagliaro, L., Piconi, L., Assaloni, R., Da Ros, R., Maier, A., Zuodar, G., Schreyer, S.A., Vick, C., Lystig, T.C., Mystkowski, P., LeBoeuf, R.C. LDL receptor but not apolipoprotein E deficiency increases diet-induced obesity and diabetes in mice. Am. J. Physiol. Endocrinol. Metab. 282: 207-214, 2002.   DOI
35 Diehl, A.M. Nonalcoholic steatohepatitis. Semin. liver. dis. 19: 220-229, 1999.
36 Akyuz, F., Demir, K., Ozdil, S., Aksoy, N., Poturoglu, S., Ibrisim, D., Kaymakoglu, S., Besisik, F., Boztas, G., Cakaloglu, Y., Mungan, Z., Cevikbas, U., Okten, A. The effects of rosiglitazone, metformin, and diet with exercise in nonalcoholic fatty liver disease. Dig. Dis. Sci. 52:2359-2367, 2007.   DOI   ScienceOn
37 Belfort, R., Harrison, S.A., Brown, K., Darland, C., Finch, J., Hardies, J., Balas, B., Gastaldelli, A., Tio, F., Pulcini, J., Berria, R., Ma, J.Z., Dwivedi, S., Havranek, R., Fincke, C., DeFronzo, R., Bannayan, G.A., Schenker, S., Cusi, K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N. Engl. J. Med. 355: 2297-2307, 2006.   DOI   ScienceOn
38 Promrat, K., Lutchman, G., Uwaifo, G.I., Freedman, R.J., Soza, A., Heller, T., Doo, E., Ghany, M., Premkumar, A., Park, Y., Liang, T.J., Yanovski, J.A., Kleiner, D.E., Hoofnagle, J.H. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology. 39: 188-196, 2004.   DOI   ScienceOn