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The Effects of Dai-saiko-to (Da-Chai-Hu-Tang) on 3T3-L1 Preadipocytes and High-Fat Diet-Induced Obese Mice

대시호탕(大柴胡湯)이 3T3-L1 지방전구세포와 고지방식이 유도 비만쥐에 미치는 영향

  • Min, Deul Le (Department of Pediatrics, College of Oriental Medicine, Wonkwang University) ;
  • Park, Eun Jung (Department of Pediatrics, College of Oriental Medicine, Wonkwang University)
  • 민들레 (원광대학교 한의과대학 소아과학교실) ;
  • 박은정 (원광대학교 한의과대학 소아과학교실)
  • Received : 2014.10.31
  • Accepted : 2014.11.17
  • Published : 2015.02.28

Abstract

Objectives This experimental study was designed to investigate the effects of Dai-saiko-to (DSH) on differentiation of 3T3-L1 preadipocytes and body weight, serum lipid levels in high-fat diet-induced obese mice. Materials and Methods Cells were incubated with DSH at an indicated concentration (0.01-1 mg/ml) for 24h, then the growth rate was assessed by MTS assay. 3T3-L1 preadipocytes were incubated in DMEM for 2 days with the indicated concentrations of DSH. On Day 6, the cells were fixed and the cellular lipid contents were assessed by Oil-Red-O staining. The expression of peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) and cytidine-cytidine-adenosine-adenosine-thymine (CCAAT)/enhancer-binding proteins ${\alpha}$ ($C/EBP{\alpha}$) as adipocyte-specific proteins were determined by real time RT-PCR and western blotting. Four-weeks old mice (wild-type C57BL/6) were used for all experiments. Body weight gain and serum lipid levels were measured in the obesity-induced mice. Results DSH did not show toxicity even at the concentration of 1 mg/ml and DSH significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. Also, DSH significantly reduced the expressions of $PPAR{\gamma}$ and $C/EBP{\alpha}$ in a dose-dependent manner. Furthermore, DSH significantly reduced body weight gain, serum glucose, total cholesterol and LDL-cholesterol contents in obesity-induced mice. Conclusions These results demonstrated that DSH inhibited 3T3-L1 preadipocyte differentiations and high-fat diet-induced obesity in mice.

Keywords

References

  1. Kang HS. A Review on the childhood obesity. Korean J Physic Educ. 2002;41(5):927-43.
  2. Kopelman PG. Obesity as a medical problem. Nature. 2000;404(6778):635-43. https://doi.org/10.1038/35007508
  3. Department of Internal Medicine, College of medicine, Seoul University. Internal medicine. Seoul: Kunja company. 1996:852-62.
  4. Nelson WE, Behrman RE, Kliegman RM, Arvin AM. Textbook of Pediatrics 15 ed. Philadelphia: WB Saunders Co. 1996:169-72.
  5. Mullins AG. The prognosis in juvenile obesity. Arch Dis Child. 1958;33(170):307-14. https://doi.org/10.1136/adc.33.170.307
  6. Serdula MK, Ivery D, Coates RJ, Freedman DS, Williamson DF, Byers T. Do obese children become obese adults? A review of the literature. Prev Med. 1993;22(2):167-77. https://doi.org/10.1006/pmed.1993.1014
  7. Shin C, Joo S, Kim J, Kim T. Prevalence and correlates of habitual snoring in high school students. Chest. 2003;124(5):1709-15. https://doi.org/10.1378/chest.124.5.1709
  8. Redline S, Tishler PV, Schluchter M, Aylor J, Clark K, Graham G. Risk factors for sleep-disordered breathing in children: Associations with obesity, race, and respiratory problems. Am J Respir Crit Care Med. 1999;159(5): 1527-32. https://doi.org/10.1164/ajrccm.159.5.9809079
  9. Sandhu J, Ben-Shlomo Y, Cole TJ, Holly J, Davey Smith G. The impact of childhood body mass index on timing of puberty, adult stature and obesity: a follow-up study based on adolescent anthropometry recorded at Christ's Hospital (1936-1964). Int J Obes. 2006;30(1):14-22. https://doi.org/10.1038/sj.ijo.0803156
  10. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman-Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001;108(2):347-53. https://doi.org/10.1542/peds.108.2.347
  11. Powell AG, Apovian CM, Aronne LJ. New drug targets for the treatment of obesity. Clin Pharmacol Ther. 2011;90(1):40-51. https://doi.org/10.1038/clpt.2011.82
  12. Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet. 2007;369 (9555):71-7. https://doi.org/10.1016/S0140-6736(07)60033-6
  13. Yin J, Zhang H, Ye J. Traditional chinese medicine in treatment of metabolic syndrome. Endocr Metab Immune Disord Drug Targets. 2008;8(2):99-111. https://doi.org/10.2174/187153008784534330
  14. Mayuantai, Zhangyinan. Huangdineijingsumen. Seoul: Sungbosa. 1975:224-330.
  15. Mayuantai, Zhangyinan. Huangdineijinglingshu. Seoul: Sungbosa. 1975:272-3.
  16. Zhongyiyanjiuyuan. Zhongyizhengzhuangjianbiezhenduanxue. Beijing: Renminweishengchubanshe. 1987:43.
  17. Hong WS. Junggyohwangjenegyung. Seoul: Dongyangyuihakyeonguwonchulpanbu. 1991:61, 94, 219-20, 275.
  18. Zhangjiebin. Jingyuequanshu. Shanghai: Shanghaikexuejishuchubanshe. 1984:194.
  19. Lichan. Bianzhuyixuerumen. Seoul: Daesungmunhwasa. 1984:108.
  20. Heo SY. Oriental and western medical study and treatment of obesity. J Oriental Rehab Med. 1997;7(1):272-86.
  21. Shin HD. Basic concepts and treatment methods of obesity in oriental medicine. Kyunghee Uihak. 1995; 11(3):257-67.
  22. Chenshiduo. Shishimilu. Seoul: Haenglimseowon. 1982: 76
  23. Lidongyuan. Dongyuanshizhongyishu Piweilun. Seoul: Daesungmunhwasa. 1983:70.
  24. Zhangji. Zhongjingquanshu. Seoul: Iljungsa. 1992:158.
  25. Cuidayong. Shanghanlunshijiang. Seoul: Daesungmunhwasa. 1995:275.
  26. Junggukjunguiyeonguwon. Jungtonggeumgweyoryak. Seoul: Uihakyeongusa. 1996:210.
  27. Song MY, Kim EK, Kong JC, Lee JH, Shin BC, Ryu DG, Kwon KB. Inhibitory effect of Daesiho-tang (Dachaihu-tang) extracts on high-fat diet-induced obesity. J Oriental Rehab Med. 2008;18(3):41-9.
  28. Yeo UH, Jo HJ, Kim HH. Effects of Daesiho-tang extract on hypertension and arterial contraction. Korean J Orient Physiol Pathol. 2005;19(6):1573-9.
  29. Park SD, Yun BG. Effects of Daesihotang and its component groups on diabetes, free radical and antioxidative defense system in alloxan induced diabetic rats. Korean J Orient Med Prescription. 2001;9(1):289-317.
  30. Lee YJ, Chi GY, Eom HS. An experimental study on the effects of Dachaihutang he wulingsan on hypertension and hyperlipidemia. Korean J Orient Med Pathol. 2000; 14(2):48-69.
  31. Han SD, Park SD. A experimental study on the effect of Kami-Daesihotang on hyperlipidemia & hypertension. J Jeahan Orient Med Acad. 1998;3(1):73-99.
  32. The Korean Society for the Study of Obesity. Clinical obesity. Seoul: Koryo Uihak. 2001:19-29.
  33. Oh KW, Jang MJ, Lee NY, Moon JS, Lee CG, Yoo MH, Kim YT. Prevalence and trends in obesity among Korean children and adolescents in 1997 and 2005. Korean J Pediatr. 2008;51(9):950-5. https://doi.org/10.3345/kjp.2008.51.9.950
  34. Ministry of Health and Welfare. Korea Health Statistics 2010: Korea National Health and Nutrition Examination Survey (KNHANES V-1). 2011.
  35. Kim JK, Oh MS, Song TW. Oriental and western study on medication treatment of obesity. Thesis Collection of Institute of korean medicine, Daejeon University. 2002;11(1):193-9.
  36. Zhangji. Zhongjingquanshu. Taibei: Jiwenshuju. 1984:142, 158.
  37. Kang SS. Right herbal prescription. Seoul: Daesung Printing. 1996:134.
  38. Shin MK. Clinical traditional herbology. Seoul: Younglimsa. 2006:176-7, 240-4, 293-6, 354-7, 400-2, 481-4, 785-7, 819-21.
  39. Jiangsuxinyixueyuan. Zhongyaodacidian. Shanghaike-xuejishuchubanshe. 1978:101-8, 655-8, 706-9, 775-9, 1093-5, 1508-11, 1832-7, 2017-21.
  40. Lee E, Lee JC. Effects of Siho(Bupleuri Radix) extracts on serum lipid composition and antioxidant system in rat fed high fat diet. Korean J Orient Med Prescription. 2003;11(1):151-9.
  41. Kim KS, Cha MH, Lee SW, Yoon YS. A study on the inhibitory effects of Scutellariae Radix on fat accumulation. Korean J Orient Med. 2003;9(2):45-54.
  42. Yoon HJ, Park YS. Effects of Scutellaria baicalensis water extract on lipid metabolism and antioxidant defense system in rats fed high fat diet. J Korean Soc Food Sci Nutr. 2010;39(2):219-26. https://doi.org/10.3746/jkfn.2010.39.2.219
  43. Ro HS, Ko WK, Park KK, Cho YH, Park HS. Antihyperlipidemic effects of Bupleuri Radix, Paeoniae Radix and Uncariae Ramulus et Uncus on experimental hyperlipidemia in rats. J Applied Pharmacol. 1997;5(1):43-7.
  44. Choi WH, Ahn JY, Kim SA Kim TW, Ha TY. Eisenia bicyclis inhibits body weight gain and fat accumulation induced by high-fat diets in mice. J Food Sci Nutr. 2010;15(4):262-6. https://doi.org/10.3746/jfn.2010.15.4.262
  45. Jang YH, Choi SW, Cho SH. Effects of Eisenia Bicyclis and its pill on serum lipid status in rats fed high fat diet. Koran J Nutr. 2008;41(1):5-12.
  46. Son YJ, Kim YS, Lee YJ. The effects of Rhei palmati Radix and Rhei undulati Radix on the blood lipids and enzymes of hypercholesterolic rats. Kor J Herbology. 1999;14(1):61-8.
  47. Ham IH, Lee UC, Lee BH, Choi HY. Lipid lowering activity of Ponciri Fructus and Aurantii Fructus Immaturus on hyperlipemia rats induced by Triton WR-133. Kor J Herbology. 2007;22(3):109-16.
  48. Ban SS, Yoon HD, Shin OC, Shin YJ, Park CS, Park JH, Seo BI. The effects of Artemisiae Capillaris, Ponciri Fructus and Cartacgi Fructus in obese rats induced by high fat diet. Kor J Herbology. 2006;21(3):55-67.
  49. Yun SG, Kim HJ, Lee MJ. Effects of Pinelliae Rhizoma on obese zucker rats' blood serum lipids and skeletal muscles fatty acid metabolism. J Korean Orient Med. 2006;27(2):211-24.
  50. Bhandari U, Sharma JN, Zafar R. The protective action of ethanolic ginger(Zingiber officinale) extract in cholesterol fed rabbits. J Ethnopharmacol. 1998;61(2):167-71. https://doi.org/10.1016/S0378-8741(98)00026-9
  51. Lee YG, Cho SY. Effect of Jujube methanol extract on benzo(a)pyrene induced hepatotoxicity. J Korean Soc Food Nutr. 1995;24(1):127-32.
  52. Fruhbeck G. Overview of adipose tissue and its role in obesity and metabolic disorders. Methods Mol Biol. 2008;456:1-22. https://doi.org/10.1007/978-1-59745-245-8_1
  53. Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab. 2000;11(8):327-32. https://doi.org/10.1016/S1043-2760(00)00301-5
  54. Flier JS, Maratos-Flier E. Obesity and the hypothalamus: novel peptides for new pathways. Cell. 1998;92(4):437-40. https://doi.org/10.1016/S0092-8674(00)80937-X
  55. Mohamed-Ali V, Pinkney JH, Coppack SW. Adipose tissue as an endocrine and paracrine organ. Int J Obes. 1998;22:1145-58. https://doi.org/10.1038/sj.ijo.0800770
  56. Green H, Meuth M. An established pre-adipose cell line and its differentiation in culture. Cell. 1974;3(2): 127-33. https://doi.org/10.1016/0092-8674(74)90116-0
  57. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev. 2000;14(11):1293-307.
  58. Chae KW, Lee JY. Comparision of decoction and distillation drug prescribed the Apricot Seed and other herbs on the proliferation and differentiation of preadipocyte from the C57BL/6 mouse. J Pediatr Korean Med. 2002; 16(2):187-97.
  59. Gregoire FM, Smas CM, Sul HS. Understanding Adipocyte Differentiation. Physiol Rev. 1998;78(3):783-809 https://doi.org/10.1152/physrev.1998.78.3.783
  60. Marcin K, Per B, Lars S, Ulf S. Impact of obesity on metabolism in men and women. J Clin Invest. 1983; 72(3):1150-62. https://doi.org/10.1172/JCI111040
  61. Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzales FJ, Spiegelman BM. C/$EBP{\alpha}$ induces adipogenesis through $PPAR_{\gamma}$: a unified pathway. Genes Dev. 2002;16(1):22-6. https://doi.org/10.1101/gad.948702
  62. Kim JB. Park JY. Molecular insights into fat cell differentiation and functional roles of adipocytokines. J Korean Soc Endocrinol Metabol. 2002;17(1):1-9.
  63. Camp HS, Ren D, Leff T. Adipogenesis and fat-cell function in obesity and diabetes. Trends Mol Med. 2002;8(9):442-7. https://doi.org/10.1016/S1471-4914(02)02396-1
  64. Tamori Y, Masugi J, Nishino N, Kasuga M. Role of peroxisome proliferator-activated receptor-${\gamma}$ in maintenance of the characteristics of mature 3T3-L1 adipocytes. Diabetes. 2002;51(7):2045-55. https://doi.org/10.2337/diabetes.51.7.2045
  65. Tanaka T1, Itoh H, Doi K, Fukunaga Y, Hosoda K, Shintani M, Yamashita J, Chun TH, Inoue M, Masatsugu K, Sawada N, Saito T, Inoue G, Nishimura H, Yoshimasa Y, Nakao K. Down regulation of peroxisome proliferatoractivated receptor-${\gamma}$ expression by inflammatory cytokines and its reversal by thiazolidinediones. Diabetologia. 1999; 42(6):702-10. https://doi.org/10.1007/s001250051218
  66. Kim HJ, Kim CH, Kim KC, Jun IS, Seo HK. The relationship between serum cholesterol level and dietary pattern. J Korean Acad Fam Med. 1996;17(10):861-8.
  67. Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan JP. The spread of the obesity epidermic in the United States, 1991-1998. J Am Med Assoc. 1999;282(16):1519-22. https://doi.org/10.1001/jama.282.16.1519
  68. Chai YH, Kim BS, Kim KH, Park HJ. A study on the relationship between obesity index and examination results among visitors of a comprehensive health screening center in Pusan. J Korean Public Health Assoc. 1993; 19(2):64-77.
  69. Gordon T, Kannel WB, Castelli WP, Dawber TR. Lipoprotein, cardiovascular disease and death: the Framingham study. Arch Inter Med. 1981;141(9):1128-31. https://doi.org/10.1001/archinte.1981.00340090024008
  70. Kook SR, Park YS, Ko YK, Kim SM, Lee DJ, Kang HC. Relationship of body fat, lipid, blood pressure, glucose in serum to waist-hip ratio between obese and normal body mass index group. J Korean Acad Fam Med. 1997;18(3):317-27.
  71. Applebaum BD, Haffner SM, Hartsook E, Luk KH, Albers JJ, Hazzard WR. Down-regulation of the low density lipoprotein receptor by dietary cholesterol. Am J Clin Nurt. 1984;39(3):360-7. https://doi.org/10.1093/ajcn/39.3.360
  72. Potter SM, Bakhit RM, Essex-sorlie DL, Weingartner KE, Chapman KM, Nelson RA, Prabhudesai M, Savage WD, Nelson AI, Winter LW. Depression of plasma cholesterol in men by consumption of baked products containing soy protein. Am J Clin Nutr. 1993;58(4):501-6. https://doi.org/10.1093/ajcn/58.4.501

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