Browse > Article
http://dx.doi.org/10.5487/TR.2011.27.4.211

Effects of Medicinal herb Extracts and their Components on Steatogenic Hepatotoxicity in Sk-hep1 Cells  

Choi, You-Jin (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Yoon, Yu-Jin (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Choi, Ho-Sung (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Park, So-Ra (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Oh, Se-Hee (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Jeong, Se-Mi (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Suh, Hyo-Ryung (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Lee, Byung-Hoon (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Publication Information
Toxicological Research / v.27, no.4, 2011 , pp. 211-216 More about this Journal
Abstract
Herbal medicines are widely used in many countries for the treatment of many diseases. Although the use of herb extracts as alternative medicine is growing, their toxicological properties have not been thoroughly investigated. In this study, we have investigated the effects of water and ethanol extracts of 18 herbs on the hepatic lipid metabolism and steatogenic hepatotoxicity. Ethanol extracts of Cirsium japonicum, Carthamus tinctorius, Rehmanniae glutinosa (preparata), Polygala tenuifolia, Foeniculum vulgare, Polygonum multiflorum, and Acorus gramineus and water extracts of Polygonum multiflorum and Rehmanniae glutinosa induced lipid accumulation in Sk-hep1 human hepatoma cells as determined by Nile red staining. These extracts increased the luciferase activity of sterol regulatory element (SRE) and decreased that of peroxisome proliferator response element (PPRE), indicating the possibilities of enhanced fatty acid synthesis and decreased fatty acid oxidation. To identify the components responsible for the fat accumulation, we tested 50 chemicals isolated from the nine herbs. Apigenin, luteolin, pectolinarin and lupeol from Cirsium japonicum, 8-methoxypsoralen and umbelliferone from Foeniculum vulgare and pomonic acid and jiocerebroside from Rehmanniae glutinosa significantly increased the accumulation of lipid droplets. These results suggest that ethanol extracts of Cirsium japonicum, Carthamus tinctorius, Rehmanniae glutinosa (preparata), Polygala tenuifolia, Foeniculum vulgare, Polygonum multiflorum, and Acorus gramineus and water extracts of Polygonum multiflorum and Rehmanniae glutinosa can cause fatty liver disease by decreasing ${\beta}$-oxidation of fatty acid and increasing lipogenesis.
Keywords
Herbal medicine; Steatosis; Nile red; $PPAR{\alpha}$; SREBP; In vitro screening;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Sudhahar, V., Kumar, S.A., Varalakshmi, P. and Sundarapandiyan, R. (2007). Mitigating role of lupeol and lupeol linoleate on hepatic lipemic-oxidative injury and lipoprotein peroxidation in experimental hypercholesterolemia. Mol. Cell Biochem., 295, 189-198.   DOI
2 Tiniakos, D.G. (2009). Liver biopsy in alcoholic and non-alcoholic steatohepatitis patients. Gastroenterol. Clin. Biol., 33, 930-939.   DOI   ScienceOn
3 Yahagi, N., Shimano, H., Hasty, A.H., Matsuzaka, T., Ide, T., Yoshikawa, T., Amemiya-Kudo, M., Tomita, S., Okazaki, H., Tamura, Y., Iizuka, Y., Ohashi, K., Osuga, J., Harada, K., Gotoda, T., Nagai, R., Ishibashi, S. and Yamada, N. (2002). Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice. J Biol. Chem., 277, 19353-19357.   DOI   ScienceOn
4 Fromenty, B., Fisch, C., Labbe, G., Degott, C., Deschamps, D., Berson, A., Letteron, P. and Pessayre, D. (1990). Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice. J. Pharmacol. Exp. Ther., 255, 1371-1376.
5 Gomez-Lechon, M.J., Donato, M.T., Martínez-Romero, A., Jimenez, N., Castell, J.V. and O'Connor, J.E. (2007). A human hepatocellular in vitro model to investigate steatosis. Chem. Biol. Interact., 165, 106-116.   DOI   ScienceOn
6 Horton, J.D., Bashmakov, Y., Shimomura, I. and Shimano, H. (1998). Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice. Proc. Natl. Acad. Sci. U.S.A., 95, 5987-5992.   DOI
7 Shimomura, I., Matsuda, M., Hammer, R.E., Bashmakov, Y., Brown, M.S. and Goldstein, J.L. (2000). Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Mol. Cell, 6, 77-86.   DOI
8 Kersten, S., Seydoux, J., Peters, J.M., Gonzalez, F.J., Desvergne, B. and Wahli, W. (1999). Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J. Clin. Invest. 103, 1489-1498.   DOI   ScienceOn
9 Liang, C.P. and Tall, A.R. (2001). Transcriptional profiling reveals global defects in energy metabolism, lipoprotein, and bile acid synthesis and transport with reversal by leptin treatment in ob/ob mouse liver. J. Biol. Chem., 276, 49066-49076.   DOI   ScienceOn
10 McMillian, M.K., Grant, E.R., Zhong, Z., Parker, J.B., Li, L., Zivin, R.A., Burczynski, M.E. and Johnson M.D. (2001). Nile Red binding to HepG2 cells: an improved assay for in vitro studies of hepatosteatosis. In Vitr. Mol. Toxicol. 14, 177-190.   DOI   ScienceOn
11 Angulo, P. (2002). Non-alcoholic Fatty Liver Disease. New Engl. J Med., 346, 1221-1231.   DOI   ScienceOn
12 Bellentani, S., Saccoccio, G., Masutti, F., Croce, L.S., Brandi, G., Sasso, F., Cristanini, G. and Tiribelli, C. (2000). Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann. Intern. Med., 132, 112-117.
13 Choi, S.I., Jeong, C.S., Cho, S.Y. and Lee, Y.S. (2007). Mechanism of apoptosis induced by apigenin in HepG2 human hepatoma cells: involvement of reactive oxygen species generated by NADPH oxidase. Arch. Pharm. Res., 30, 1328-1335.   DOI   ScienceOn
14 Eadie, M.J., Hooper, W.D. and Dickinson, R.G. (1988). Valproateassociated hepatotoxicity and its biochemical mechanisms. Med. Toxicol. Adverse Drug Exp., 3, 85-106.   DOI
15 Costet, P., Legendre, C., More, J., Edgar, A., Galtier, P. and Pineau, T. (1998). Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis. J Biol. Chem., 273, 29577-29585.   DOI
16 Deboyser, D., Goethals, F., Krack, G. and Roberfroid, M. (1989). Investigation into the mechanism of tetracycline-induced steatosis: study in isolated hepatocytes. Toxicol. Appl. Pharmacol., 97, 473-479.   DOI   ScienceOn
17 Domitroviae, R., Jakovac, H., Tomac, J. and Sain, I. (2009). Liver fibrosis in mice induced by carbon tetrachloride and its reversion by luteolin. Toxicol. Appl. Pharmacol., 241, 311-321.   DOI   ScienceOn