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http://dx.doi.org/10.14374/HFS.2014.22.1.093

Effects of Samhwangsasim-tang on obesity-related metabolic disease in mice  

Lee, Ju-Young (Dept. of Formula Science, College of Korean Medicine, Sangji University)
Kook, Yoon-Bum (Dept. of Formula Science, College of Korean Medicine, Sangji University)
Publication Information
Herbal Formula Science / v.22, no.1, 2014 , pp. 93-104 More about this Journal
Abstract
Objectives : Samhwangsasim-tang (SHSST) is a traditional Korean medication, which has been used in Korea for treatment of hypertension and chest pain. Hyperlipidemia and inflammation could influence hypertension and chest pain. This study investigated whether and how SHSST reduces the hyperlipidemia and inflammation related to high-cholesterol diet-induced obesity in rats. Methods : Mice were divided randomly into four groups: the normal diet group, high-cholesterol diet group, low dose treatment group supplemented with 30% ethanol extract of SHSST (L) and high dose treatment group supplemented with 80% ethanol extract of SHSST (H). L and H groups were orally administered with SHSST at the dose of 50mg/kg a day respectively and others were administered with the same volume of physiological saline. Results : Administration of SHSST resulted in a decrease in serum levels of total cholesterol and low-density lipoprotein. Expression of hepatic genes(SREBP2, LXR, LDLR, and HMG-CoA) related with cholesterol metabolism was also suppressed. In addition, SHSST decreased the expression of inflammation-related gene (TNF-${\alpha}$, IL-6, ICAM-1, VCAM-1, TGF-${\beta}1$ and fibronectin). Histological examinations also showed that the size of the adipocytes was smaller in the SHSST treated group than in the high-colesterol diet group. In an in vitro study, SHSST inhibited the production of nitric oxide in a concentration-dependent manner. Conclusions : This study indicates that SHSST has anti-hyperlipidemia and anti-inflammatory effects. It may also suggest that SHSST may be alternative therapy for treatment of hyperlipidemia and its complications.
Keywords
Samhwangsasim-tang (SHSST); anti-hyperlipidemia; anti-inflammatory; obesity; alternative therapy;
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1 Postic C and Girard J. The role of the lipogenic pathway in the development of hepatic steatosis. Diabetes Metab. 2008:346,643-48.
2 Goldstein, J. L. and Brown, M. S. : Progress in understanding the LDL receptoe and HMG-CoA reductase, two membrane proteins that regulate the plama cholesterol. J. Lipid Res. 1984;25:1450-461.
3 Yokoyama, C., Wang, X., Briggs, M.R., Admon, A., Wu, J., Hua, X., Goldstein, J. L. and Brown, M.S. SREBP-1, a basic-helix-loophelix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell. 1984;75:187-97.
4 Park SJ, Kim JY, Jang YP, Cho YW, Ahn EM, Baek NI, Lee KT. Inhibition of LPS induced iNOS, COX-2 and cytokines expression by genistein-4'-O-${\alpha}$-L-rhamnopyranosyl-(1-2)-${\beta}$-D-glucopyranoside through the NF-${\kappa}B$ inactivation in RAW 264.7 cells. Kor. J. Pharmacogn. 2007;38(4):339-48.   과학기술학회마을
5 Pearson JD. Endothelial cell function and thrombosis. Baillieres Best Pract Res Clin Haematol. 1999;12:329-41.   DOI   ScienceOn
6 Libby, P., Ridker, P. M., Maseri, A. Inflammation and atherosclerosis. Circulation. 2002:135-43.
7 O'Brien KD, Allen MD, McDonald TO, Chait A, Harlan JM, Fishbein D, McCarty J, Furgerson M, Hudkins K, Benjamin CD, Lobb R, Alpers CE. Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. J Clin Invest. 1993;92:945-51.   DOI   ScienceOn
8 Horton, J.D., Bashmakov, Y., Shimomura, I., Shimano, H. Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice: Proc Natl Acad Sci. 1998;95(11):5987-992.   DOI   ScienceOn
9 Shimomura, I., Shimano, H., Horton, J.D., Goldstein, J.L., Brown, M.S. Differential Expression of Exons 1a and 1c in mRNAs for Sterol Regulatory Element Binding Protein-1 in Human and Mouse Organs and Cultured Cells: J Clin Invest. 1997;99(5):838-45.   DOI   ScienceOn
10 Horton, J.D., Goldstein, J.L., Brown, M.S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver: J Clin Invest. Cell. 2002;109:1125-131.   DOI
11 Yahagi, N., Shimano, H., Hasty, A.H., Matsuzaka, T., Ide, T., Yoshikawa, T. Absence of sterol regulatory element-binding protein-1 (SREPB-1) ameliorates Jorates fatty livers but not obesity or insulin resistance in Lepob/Lepob mice. J Biol Chem. 2002;277(22):19353-9357.   DOI   ScienceOn
12 Baranowski M. Biological role of liver X receptors. J Physiol Pharmacol. 2008;59 Suppl7:31-55.
13 Ulven SM, Dalen KT, Gustafsson JA and Nebb HI. LXR is crucial in lipid metabolism. Prostaglandins Leukot Esset Fatty Acids. 2005;731:59-63.
14 Rapa JJ and Mangelsdorf DJ, The role of orphan nuclear receptors in regulation of cholesterol homeostasis. Annu Rev Cell Dev Biol. 2000;16: 459-81.   DOI   ScienceOn
15 Schultz JR, Tu H, Luk A, Rapa JJ, Medina JC, Li L. Role of LXRs in control of lipogenesis. Genes DEV. 2000;1422,2831-838.
16 Grefhorst A, Elzinga BM, Voshol PJ, Plosch T, Kok T, Bloks VW., Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J Biol Chem. 2002;27737,34182-4190.
17 Chen G, Liang G, Ou J, Goldstein JL and Brown MS. Cental tole for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci USA. 2004: 10131,11245-1250.
18 Oh SW. Effects of Jowiseungcheung-tang (JWSCT) extract on the lipid metabolism, anti-oxidation and inflammatory response in obesity rat fed high fat diet. Sangji University Graduate School. 2011.
19 http://kostat.go.kr
20 Eberle D, Hegarty B, Bossard P, Ferre P and Foufelle F. SREBP transcription factors: mater regulators of lipid homeostasis. Biochimie. 2004; 839-48,8611.
21 Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T, Westerbacka J, Sovijarvi A, Halavaara J, Yki-Jarvinen H. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab. 2002;87:3023-028.   DOI
22 Korean Medical Colleges Liver School Professor Edit. Liver Internal Medicine 4th Edition. Seoul:Korean Medicine Study Publishing Department. 2001:316-19.
23 Sa JM, Wang GP. Geumgweyoryakselfstudy. Beijing:zygjcbs. 1988:146-47.
24 Shah, C.S., J.S. Qardy and J.G. Bhatt. Qualitative and quantitative evaluation of anthraquinone derivatives in Indian rhubarb. Planta Med. 1972;22: 103-08.   DOI
25 Krakauer T, Li BQ, Young HA. The flavonoid baicalin inhibits superantigen-induced inflammatory cytokines and chemokines. FEBS Lett, 2001;29,500(1-2):52-5.   DOI   ScienceOn
26 Department of Internal Medicine, College of medicine, Seoul University. Internal medicine. Seoul:Kunja company. 1996:852-62.
27 Niu C, Chen C, Chen L, Cheng K, Yeh C, Cheng J. Decrease of blood lipids induced by Shan-Zha (fruit of Crataegus pinnatifida) is mainly related to an increase of $PPAR{\alpha}$ in liver of mice fed high-fat diet. Horm Metab Res. 2011;43(9):625-30.   DOI   ScienceOn
28 Gwakaechun. Canon of Medicine. Tianjin:Tianjin Science and Technology Publishing. 1981:54, 87, 183, 194, 282.
29 Heo SY. Oriental and Western Medical Study on the investigation and treatment of Obesity. J Ori Rehab Med. 1997;7(1):272-86.
30 Sung YY, Yoon T, Yang WK, Kim SJ, Kim HK. Anti-obesity effects of Geranium thunbergii extract via improvement of lipid metabolism in high-fat diet-induced obese mice. Mol Med Report. 2011;4(6):1107-113.
31 Park WH. Effects of stem bark extracts of Cornus walteri Wanger on the lipid lowering, anti-oxidative activity and concentration of proinflammatory cytokines in rat fed high fat diet. Sangji University Graduate School. 2009.
32 Kong IP. Effects of Ojeoksangamibang on the Lipid Metabolism, Anti-oxidation and Concentration of Proinflammatory Cytokines in High Fat Diet Induced Obese Rats. Sangji University Graduate School. 2011.
33 Park SH, Jeon WK, Kim SH, Kim HJ, Park DI, Cho YK, Sung IK, Sohn CI, Keum DK, Kim BI. Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults. J Gastroenterol Hepatol. 2006;21:138-43.   DOI   ScienceOn
34 Asselah T, Rubbia-Brandt L, Marcellin P, Negro F. Steatosis in chronic hepatitis C: why does it really matter. Gut. 2006;55:123-30.   DOI   ScienceOn
35 Jun DW. Non-alcoholic fatty liver disease. Korean J Hepatol. 2011;17: S332-36.
36 Yoon KR. Biological effects of Allium monanthum extracts on the lipid metabolism, anti-oxidation and pro-inflammatory cytokines production in rat fed high fat diet. Sangji University Graduate School. 2011.
37 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. 2003;37:917-23.   DOI   ScienceOn
38 Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, McCullough AJ, Natale S, Forlani G, Melchionda N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001;50:1844-850.   DOI   ScienceOn