Artemisia capillaries Herbal Acupuncture Improves Metabolic Abnormalities in High Fat Diet-induced Obese ICR Mice

인진약침이 고지방식이유도 비만 ICR Mice에서 항비만 및 대사이상 개선에 미치는 영향

  • Youh, Eun-Joo (Department of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Seo, Byung-Kwan (Department of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Huang, Bo (College of Pharmacy, Kyung Hee University) ;
  • Kim, Jong-In (Department of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Kang, Sung-Keel (Department of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University)
  • 유은주 (경희대학교 한의과대학 침구학교실) ;
  • 서병관 (경희대학교 한의과대학 침구학교실) ;
  • 황보 (경희대학교 약학대학) ;
  • 김종인 (경희대학교 한의과대학 침구학교실) ;
  • 강성길 (경희대학교 한의과대학 침구학교실)
  • Received : 2010.11.02
  • Accepted : 2011.01.23
  • Published : 2011.02.20

Abstract

목적 : 인진약침이 고지방식이로 유발된 비만 ICR mice에서 비만 및 동반 대사이상에 미치는 효과와 그 기전을 연구하고자 한다. 방법 : 인진약침의 비만 예방효과를 검증하기 위하여, 4주간 고지방식이를 급여하면서 150mg/kg 또는 300mg/kg의 인진약침을 양측 비수($BL_{20}$)에 교대로 매일 피하에 시술하였다. 또한 인진약침의 비만 치료효과를 검증하기 위하여, 4주간 고지방식이를 급여한 비만 ICR mice에 추가 4주간 고지방식이를 유지하면서 300 mg/kg 인진약침액과 vehicle control로써 등량의 distilled water를 양측 비수($BL_{20}$)에 교대로 매일 피하에 약침시술하였다. 인진약침의 항비만효과와 기전을 알아보기 위해, 체중, blood glucose, insulin, total cholesterol, triglyceride, non-esterified fatty acid (NEFA), AST, ALT levels 등 대사지표를 측정하고 부고환조직의 조직학적 관찰을 시행하였으며, AMPK activation과 adipocyte differentiation, fatty acid ${\beta}$-oxidation 및 thermogenesis와 관련된 gene expressions을 평가하였다. 결과 : 인진약침의 치료를 통하여 고지방식이 급여로 인한 체중의 증가가 억제되었을 뿐만 아니라, 비만 ICR mice의 체중을 감소시켰으며, glucose 및 lipid homeostasis를 개선시켰으며 지방조직의 증식을 억제하였다. AMPK의 phosphorylation과 CPT-1 및 UCP2의 발현을 증가시켰으며, PPAR-${\gamma}$, C/EBP${\alpha}$, aP2, LPL,FAS, SCD-1의 발현을 억제하였다. 결론 : 인진약침은 고지방식이 유도 동물모델에서 비만 및 동반 대사이상을 개선시키는 효과가 있으며, 이는 식이억제에 의한 2차적 효과라기 보다는 energy expenditure를 증가시키고, pre-adipocyte differentiation 및 proliferation을 억제하며, lipogenesis를 억제하고 lipolysis를 증가시키는 효과에 의한 것으로 사료된다.

Keywords

References

  1. Park HS. Practical Therapeutics : pathophysiology of obesity and energy control for obesity treatment. J Korean Acad Fam Med. 2000 ; 22(8) : 1287-95.
  2. Seidell JC. Obesity, insulin resistance and diabetes- a worldwide epidemic. Br J Nutr. 2000 ; 83 Suppl 1 : S5-8.
  3. WHO. Obesity and overweight. 2009.
  4. Kim DM, Ahn CW, Nam SY. Prevalence of obesity in Korea. Obes Rev. 2005 ; 6(2) : 117-21. https://doi.org/10.1111/j.1467-789X.2005.00173.x
  5. Park HS, Park CY, Oh SW, Yoo HJ. Prevalence of obesity and metabolic syndrome in Korean adults. Obes Rev. 2008 ; 9(2) : 104-7. https://doi.org/10.1111/j.1467-789X.2007.00421.x
  6. Hong EG. Pathophysiology of Adult Obesity and Related-disease. Korean Clinical Diabetes. 2008 ; 9(3) : 148-52.
  7. Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, Van Pelt RE, Wang H, Eckel RH. The Metabolic Syndrome. Endocr Rev. 2008 ; 29(7) : 777-822. https://doi.org/10.1210/er.2008-0024
  8. Sullivan PW, Ghushchyan VH, Ben-Joseph R. The impact of obesity on diabetes, hyperlipidemia and hypertension in the United States. Qual Life Res. 2008 ; 17(8) : 1063-71. https://doi.org/10.1007/s11136-008-9385-7
  9. Peebles R. Adolescent obesity : etiology, office evaluation, and treatment. Adolesc Med State Art Rev. 2008 ; 19(3) : 380-405.
  10. Stefan N, Kantartzis K, Machann J, Schick F, Thamer C, Rittig K, Balletshofer B, Machicao F, Fritsche A, Haring HU. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med. 2008 ; 168(15) : 1609-16. https://doi.org/10.1001/archinte.168.15.1609
  11. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith Jr SC, Spertus JA, Costa F. Diagnosis and management of the metabolic syndrome. An American Heart Asciation/ National Heart, Lung, and Blood Institute Scientific Statement. Executive summary. Cardiol Rev. 2005 ; 13(6) : 322-7.
  12. Weir GC, Bonner-Weir S. A dominant role for glucose in beta cell compensation of insulin resistance. J Clin Invest. 2007 ; 117(1) : 81-3. https://doi.org/10.1172/JCI30862
  13. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000 ; 106(4) : 473-81. https://doi.org/10.1172/JCI10842
  14. Boden G. Interaction between free fatty acids and glucose metabolism. Curr Opin Clin Nutr Metab Care. 2002 ; 5(5) : 545-9. https://doi.org/10.1097/00075197-200209000-00014
  15. Montecucco F, Steffens S, Mach F. Insulin resistance : a proinflammatory state mediated by lipid-induced signaling dysfunction and involved in atherosclerotic plaque instability. Mediators Inflamm. 2008 ; 2008 : 767623.
  16. Ballinger A, Peikin SR. Orlistat : its current status as an anti-obesity drug. Eur J Pharmacol. 2002 ; 440(2-3) : 109-17.
  17. Drew BS, Dixon AF, Dixon JB. Obesity management : update on orlistat. Vasc Health Risk Manag. 2007 ; 3(6) : 817-21.
  18. Poston WS, Foreyt JP. Sibutramine and the management of obesity. Expert Opin Pharmacother. 2004 ; 5(3) : 633-42. https://doi.org/10.1517/14656566.5.3.633
  19. Tziomalos K, Krassas GE, Tzotzas T. The use of sibutramine in the management of obesity and related disorders : an update. Vasc Health Risk Manag. 2009 ; 5(1) : 441-52.
  20. Halford JC. Obesity drugs in clinical development. Curr Opin Investig Drugs. 2006 ; 7(4) : 312-8.
  21. Melnikova I, Wages D. Anti-obesity therapies. Nat Rev Drug Discov. 2006 ; 5(5) : 369-70. https://doi.org/10.1038/nrd2037
  22. Karamadoukis L, Shivashankar GH, Ludeman L, Williams AJ. An unusual complication of treatment with orlistat. Clin Nephrol. 2009 ; 71(4) : 430-2.
  23. Thurairajah PH, Syn WK, Neil DA, Stell D, Haydon G. Orlistat (Xenical)-induced subacute liver failure. Eur J Gastroenterol Hepatol. 2005 ; 17(12) : 1437-8. https://doi.org/10.1097/01.meg.0000187680.53389.88
  24. Mayer MA, Hocht C, Puyo A, Taira CA. Recent advances in obesity pharmacotherapy. Curr Clin Pharmacol. 2009 ; 4(1) : 53-61 https://doi.org/10.2174/157488409787236128
  25. Park MY, Lee KS, Sung MK. Effects of dietary mulberry, Korean red ginseng, and banaba on glucose homeostasis in relation to PPAR-alpha, PPAR-gamma, and LPL mRNA expressions. Life Sci. 2005 ; 77(26) : 3344-54. https://doi.org/10.1016/j.lfs.2005.05.043
  26. Han LK, Kinura Y, Okuda H. Anti-obesity effects of natural products. Stud Nat Prod Chem. 2005 ; 30 : 79-110.
  27. Rayalam S, Della-Fera MA, Baile CA. Phytochemicals and regulation of the adipocyte life cycle. J Nutr Biochem. 2008 ; 19(11) : 717-26. https://doi.org/10.1016/j.jnutbio.2007.12.007
  28. Han KH, Jeon YJ, Athukorala Y, Choi KD, Kim CJ, Cho JK, Sekikawa M, Fukushima M, Lee CH. A water extract of Artemisia capillaris prevents 2, 2'-azobis(2-amidinopropane. dihydrochlorideinduced liver damage in rats. J Med Food. 2006 ; 9(3) : 342-7. https://doi.org/10.1089/jmf.2006.9.342
  29. Hu YQ, Tan RX, Chu MY, Zhou J. Apoptosis in human hepatoma cell line SMMC-7721 induced by water-soluble macromolecular components of Artemisia capillaris Thunberg. Jpn J Cancer Res. 2000 ; 91(1) : 113-7. https://doi.org/10.1111/j.1349-7006.2000.tb00867.x
  30. Koo HN, Hong SH, Jeong HJ, Lee EH, Kim NG, Choi SD, Ra KW, Kim KS, Kang BK, Kim JJ, Oh JG, Kim HM. Inhibitory effect of Artemisia capillaris on ethanol-induced cytokines (TNF-alpha, IL-1alpha. secretion in Hep G2 cells. Immunopharmacol Immunotoxicol. 2002 ; 24(3) : 441-53. https://doi.org/10.1081/IPH-120014728
  31. Yang CC, Lee MR, Hsu SL, Chang CMJ. Supercritical fluids extraction of capillarisin from Artemisia capillaris and its inhibition of in vitro growth of hepatoma cells. J Supercritical Fluids. 2007 ; 42 : 96-103. https://doi.org/10.1016/j.supflu.2006.12.022
  32. Cha JD, Jeong MR, Jeong SI, Moon SE, Kim JY, Kil BS, Song YH. Chemical composition and antimicrobial activity of the essential oils of Artemisia scoparia and A. capillaris. Planta Med. 2005 ; 71(2) : 186-90. https://doi.org/10.1055/s-2005-837790
  33. Kil BS, Kim YS, Yun KW. Allelopathic effects of growth inhibitor from Artemisia princeps var. orientalis. Kor J Ecol. 1991 ; 14 : 121-35.
  34. Kim JO, Kim YS, Lee JH, Kim MN, Rhee SH, Moon SH, Park KY. Antimutagenic effect of the major volatile compounds identified from mugwort (Artemisia asictica nakai) leaves. J Kor Soc Food Nutr. 1992 ; 21 : 308-13.
  35. Shan B, Cai YZ, Brooks JD, Corke H. The in vitro antibacterial activity of dietary spice and medicinal herb extracts. Int J Food Microbiol. 2007 ; 117(1) : 112-9. https://doi.org/10.1016/j.ijfoodmicro.2007.03.003
  36. Lee J, Chae K, Ha J, Park BY, Lee HS, Jeong S, Kim MY, Yoon M. Regulation of obesity and lipid disorders by herbal extracts from Morus alba, Melissa officinalis, and Artemisia capillaris in high-fat diet-induced obese mice. J Ethnopharmacol. 2008 ; 115(2) : 263-70. https://doi.org/10.1016/j.jep.2007.09.029
  37. Hong JH, Hwang EY, Kim HJ, Jeong YJ, Lee IS. Artemisia capillaris inhibits lipid accumulation in 3T3-L1 adipocytes and obesity in C57BL/6J mice fed a high fat diet. J Med Food. 2009 ; 12(4) : 736-45. https://doi.org/10.1089/jmf.2008.1240
  38. Departments of Acupuncture & Moxibustion. Textbook of Acupuncture & Moxibustion (1). Seoul : Jipmundang. 2008 : 135.
  39. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment : insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 ; 28(7) : 412-9. https://doi.org/10.1007/BF00280883
  40. Astrup A. The role of dietary fat in the prevention and treatment of obesity. Efficacy and safety of low-fat diets. Int J Obes Relat Metab Disord. 2001 ; 25 Suppl 1 : S46-50.
  41. Stubbs RJ, Harbron CG, Murgatroyd PR, Prentice AM. Covert manipulation of dietary fat and energy density : effect on substrate flux and food intake in men eating ad libitum. Am J Clin Nutr. 1995 ; 62(2) : 316-29.
  42. Mikkelsen PB, Toubro S, Astrup A. Effect of fat-reduced diets on 24-h energy expenditure : comparisons between animal protein, vegetable protein, and carbohydrate. Am J Clin Nutr. 2000 ; 72(5) : 1135-41.
  43. Lammert O, Grunnet N, Faber P, Bjornsbo KS, Dich J, Larsen LO, Neese RA, Hellerstein MK, Quistorff B. Effects of isoenergetic overfeeding of either carbohydrate or fat in young men. Br J Nutr. 2000 ; 84(2) : 233-45.
  44. Colditz GA, Willett WC, Stampfer MJ, Manson JE, Hennekens CH, Arky RA, Speizer FE. Weight as a risk factor for clinical diabetes in women. Am J Epidemiol. 1990 ; 132(3) : 501-13.
  45. Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN. Diet-induced type II diabetes in C57BL/6J mice. Diabetes. 1988 ; 37(9) : 1163-7. https://doi.org/10.2337/diabetes.37.9.1163
  46. Thupari JN, Kim EK, Moran TH, Ronnett GV, Kuhajda FP. Chronic C75 treatment of dietinduced obese mice increases fat oxidation and reduces food intake to reduce adipose mass. Am J Physiol Endocrinol Metab. 2004 ; 287(1) : E97-E104. https://doi.org/10.1152/ajpendo.00261.2003
  47. Yun SN, Moon SJ, Ko SK, Im BO, Chung SH. Wild ginseng prevents the onset of high-fat diet induced hyperglycemia and obesity in ICR mice. Arch Pharm Res. 2004 ; 27(7) : 790-6. https://doi.org/10.1007/BF02980150
  48. Sone H, Suzuki H, Takahashi A, Yamada N. Disease model : hyperinsulinemia and insulin resistance. Part A-targeted disruption of insulin signaling or glucose transport. Trends Mol Med. 2001 ; 7(7) : 320-2. https://doi.org/10.1016/S1471-4914(01)02041-X
  49. Misra P, Chakrabarti R. The role of AMP kinase in diabetes. Indian J Med Res. 2007 ; 125(3) : 389-98.
  50. Steinberg GR, Kemp BE. AMPK in Health and Disease. Physiol Rev. 2009 ; 89(3) : 1025-78. https://doi.org/10.1152/physrev.00011.2008
  51. Kiens B. Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiol Rev. 2006 ; 86(1) : 205-43. https://doi.org/10.1152/physrev.00023.2004
  52. Departments of Herbology. Textbook of Herbology. Seoul : Younglimsa. 2004 : 372-3.
  53. Elinos-Baez CM, Leon F, Santos E. Effects of coumarin and 7OH-coumarin on bcl-2 and Bax expression in two human lung cancer cell lines in vitro. Cell Biol Int. 2005 ; 29(8) : 703-8. https://doi.org/10.1016/j.cellbi.2005.04.003
  54. Sheu SJ, Chieh CL, Weng WC. Capillary electrophoretic determination of the constituents of Artemisiae Capillaris Herba. J Chromatogr A. 2001 ; 911(2) : 285-93. https://doi.org/10.1016/S0021-9673(01)00513-1