DOI QR코드

DOI QR Code

Anti-obesity Effects of Galgeun-tang in High Fat Diet Induced Obese Mice Model

갈근탕이 고지방 식이 유발 백서 모델에 미치는 항비만 효과

  • Received : 2016.03.28
  • Accepted : 2016.04.18
  • Published : 2016.04.30

Abstract

Objectives To investigate anti-obesity effects of Galgeun-tang, an herbal formula, in high fat diet induced obese mice model. Methods 24 Male C57Bl/6J mice were randomly assigned to normal group fed with normal research diet (NOR, n=6), high fat diet control group treated with water (HFD, n=6), high fat diet group treated with Orlistat (ORL, n=6, Orlistat 10 mg/kg), and high fat diet group treated with Galgeun-tang (GGT, n=6, Galgeun-tang 700 mg/kg). 12 weeks later, body weight, fat weight, liver weight, blood glucose, total cholesterol, triglyceride, HDL, ALT, AST, obesity related neuropeptides and adipokines, ratio of gut microbiota, and histopathology of liver were evaluated. Results In the GGT group, 1. body weight gain, liver weight gain, and total fat weight gain were significantly less than those in the HFD group. 2. blood glucose level was significantly lower and insulin level was significantly higher than in the HFD group. 3. total cholesterol level and triglyceride (TG) level were significantly lower and high density lipoprotein (HDL) level was significantly higher than in the HFD group. 4. appetite-promoting ARC neuropeptides such as Agrp and Npy were significantly less and appetite-inhibiting ARC neuropeptide, Cart was significantly more than in the HFD group in qRT-PCR analysis. 5. adiponectin level and visfatin level were significantly higher, and resistin level and leptin level was significantly lower than in the HFD group. 6. the relative level of Bacteroidetes was significantly higher, and the relative level of Firmicutes was significantly lower than in the HFD group. 7. the increase of adipose tissue was significantly more inhibited than in the HFD group. Conclusions The present study showed that Glageun-tang exerts anti-obesity effects in that it. 1. inhibited the increase in body weight, liver weight, and total fat weight. 2. decreased the level of TG, and increased the level of HDL. 3. influenced neuropeptides and adipokines that are important in regulating food intake and changes of body weight. 4. modified the beneficial quantitative changes in gut microbiota suppressing the tendency toward obesity.

Keywords

Galgeun-tang;Obesity;High fat diet;qRT-PCR;ARC neuropeptide;adiponectin;gut microbiota

References

  1. Hahn D, Payne W, Lucas E. Focus on health. 11thed. New York: McGrow Hill Humanities. 2013:125-53.
  2. Kawadoki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocrine Reviews. 2005:26(3):439-51. https://doi.org/10.1210/er.2005-0005
  3. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7(8):941-6. https://doi.org/10.1038/90984
  4. Kim BS, Song MY, Kim HJ. The anti-obesity effect of Ephedra sinica through modulation of gut microbiota in obese Korean women. Journal of Ethnopharmacology 2014;152:532-9. https://doi.org/10.1016/j.jep.2014.01.038
  5. Elmquist JK, Coppari R, Balthasar N, Ichinose M, Lowell BB. Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. J Comp Neurol 2005;493:63-71. https://doi.org/10.1002/cne.20786
  6. Morton GJ, Cummings DE, Baskin DG, Barsh GS & Schwartz MW. Central nervous system control of food intake and body weight. Nature 2006;443:289-95. https://doi.org/10.1038/nature05026
  7. Yu Y, Deng C, Huang XF. Obese reversal by a chronic energy restricted diet leaves an increased Arc NPY/AgRP, but no alteration in POMC/CART, mRNA expression in diet-induced obese rat. Behavioural Brain Research 2009;205:50-6. https://doi.org/10.1016/j.bbr.2009.07.003
  8. Park Young-Soon. Herbal Pharmacology Commentary. Seoul: Academy books, 2002:196-202.
  9. Tang W, Eisenbrand G. Chinese drug of plant originchemistry, pharmacology and use in traditional and modern medicine. New York: Springer Berlin, Heidelberg. 1992:797-803.
  10. Zhu YP. Chinese materia medica-chemistry, pharmacology and applications. Amsterdam: Harwood Academic Publishers. 1998:92-6.
  11. Textbook Compilation Committee of college of Korean Medicine. Herbology. Seoul : Younglim. 1991:148-9.
  12. Shin JM, Kim YO, Baek SH. Free radical scavenging activity and kinetic behavior of the galgeuntang water extract. ORIental Pharm. Exp. Med. 2008;8:32-8. https://doi.org/10.3742/OPEM.2008.8.1.032
  13. Wang X, Wu J, Chiba H, Umegaki K, Yamada K, Ishimi Y. Puerariae radix prevents bone loss in ovariectomized rat. J Bone Miner Metab. 2003;21(5):268-75. https://doi.org/10.1007/s00774-003-0420-z
  14. Hsu FK, Liu IM, Kuo DH, Chen WC, Su HC, Cheng JT. Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats. J Nat Prod. 2003;66(6):788-92. https://doi.org/10.1021/np0203887
  15. Qi W, Weber CR, Wasland K, Savkovic SD. Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity. BMC Cancer. 2011;11(1):219. https://doi.org/10.1186/1471-2407-11-219
  16. Kang SC, Lee CM, Choi H, Lee JH, Oh JS, Kwak JH, Zee OP. Evaluation of ORIental medicinal herbs for estrogeic and antiproliferative activities. Phytother Res. 2006;20(11):1017-9. https://doi.org/10.1002/ptr.1987
  17. Shin YS, Hwang GS. The effects of Pueraria lobata extract on gene expression in liver tissue of rat with estrogen- deficient obesity. Journal of Society of Preventive Korean Medicine. 2014;18(3):119-30.
  18. Shin Gil-Goo. Shenshi Herbal Medicine. Soomoonsa. 1988:211.
  19. Shin Min-Gyo. Clinical Herbal Medicine. Younglimsa. 1997:322, 658, 693,770.
  20. Paul GS, Mary LH, Sally CM, Margaret M, Walter AM, Marika JS, Shannon LR, Lara J, James G. Efficacy and Safety of ephedra and ephedrine for weight loss and arthletic performance: a meta-analysis. JAMA. 2003; 289(12):1537-45.
  21. Kim HJ , Han CH, Lee EJ, Song YK, Shin BC, Kim YK. A Clinical Practice Guideline for Ma-huang(Ephedra sinica) Prescription in Obesity. Journal of Society of Korean Medicine for Obesity Research 2007;7(2):30.
  22. Sarah F. Leibowitz, Katherine E. Wortley. Hypothalamic control of energy balance: different peptides, different functions. Peptides 2004;25:473-504. https://doi.org/10.1016/j.peptides.2004.02.006
  23. Hwang MJ, Shin HD, Song MY. Literature review of herbal medicines on treatment of obesity since 2000 - mainly about ephedra herba. J Korean Med Obes Res. 2007;7:39-54.
  24. Song MY, Kim HJ. Analysis of Main Single Medicinal Herbs for Anti-Obesity. Journal of Society of Korean Medicine for Obesity Research 2013;13(2):51-7.
  25. Park JH, Lee MJ, Song MY, Bose S, Shin BC, Kim HJ. Efficacy and safety of mixed oriental herbal medicines for treating human obesity: a systematic review of randomized clinical trials. J Med Food. 2012;15(7): 589-97. https://doi.org/10.1089/jmf.2011.1982
  26. 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
  27. Hasani-Ranjbar S, Nayebi N, Larijani B, Abdollahi M. A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. World J Gastroenterol. 2009;15(25):3073-85. https://doi.org/10.3748/wjg.15.3073
  28. Xia Q, Grant S. The genetics of human obesity. Ann N Y Acad Sci. 2013;1281(1):178-90. https://doi.org/10.1111/nyas.12020
  29. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444(7121):840-46. https://doi.org/10.1038/nature05482
  30. Crawley JN, Belknap JK, Collins A, Crabbe J C, Frankel W, Henderson N, Hitzemann RJ, Maxson SC, Miner LL, Silva AJ, Wehner JM, Wynshaw-Boris A, Paylor R. Behavioral phenotypes of inbred mouse strains : implications and recommendations for molecular studies. Psychopharmacology 1997;132:107-24. https://doi.org/10.1007/s002130050327
  31. Schele E., Grahnemo L., Anesten F., Hallen A, Backhed F., Jansson JO. The Gut Microbiota Reduces Leptin Sensitivity and the Expression of the Obesity-Suppressing Neuropeptides Proglucagon (Gcg) and Brain-Derived Neurotrophic Factor (Bdnf) in the Central Nervous System. Endocrinology 2013;154(10):3643-51. https://doi.org/10.1210/en.2012-2151
  32. Yan QW., Yang Q, Mody N, Graham TE, Hsu CH, Xu Z, Houstis NE, Kahn BB, Rosen ED. The Adipokine Lipocalin2 Is Regulated by Obesity and Promotes Insulin Resistance. Diabetes 2007;56:2533-40. https://doi.org/10.2337/db07-0007
  33. Kotnik P, Fischer-Posovszky P, Wabitsch M. RBP4: a controversial adipokine. European Journal of Endocrinology 2011;165:703-11. https://doi.org/10.1530/EJE-11-0431
  34. Becker KL. Principles and practice of endocrinology and metabolism. Lippincott Williams & Wilkins 2001:1689.
  35. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. Visfatin: A Protein Secreted by Visceral Fat That Mimics the Effects of Insulin. Science 2005;307(5708):426-30. https://doi.org/10.1126/science.1097243
  36. Klotinga N, Berndta J, Kralischa S, Kovacsa P, Fasshauera M, Schonc MR, Stumvolla M, Bluher M. Vaspin gene expression in human adipose tissue: Association with obesity and type 2 diabetes. Biochemical and Biophysical Research Communications 2006;339(1):430-6. https://doi.org/10.1016/j.bbrc.2005.11.039
  37. Trayhurn P, Beattie JH Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proceedings of the Nutrition Society 2001;60:329-39.
  38. Park JH, Kim HJ, Lee MJ. The Role of Gut Microbiota in Obesity and Utilization of Fermented Herbal Extracts. Journal of Society of Korean Medicine for Obesity Research 2009;9(1):1-14.
  39. Backhed F, Crawford PA. Coordinated regulation of the metabolome and lipidome at the host-microbial interface. Biochim Biophys Acta 2010;1801:240-5. https://doi.org/10.1016/j.bbalip.2009.09.009
  40. Turnbaugh PJ, Backhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 2008;3:213-23. https://doi.org/10.1016/j.chom.2008.02.015
  41. Bajzar M, Seeley RJ. Physiology: obesity and gut flora. Nature 2006;444:1009-10. https://doi.org/10.1038/4441009a
  42. Kang JH , Yun SI, Park MH, Park JH, Jeong SH, Park HO. Anti-obesity effect of Lactobacillus gasseri BNR17 in high-source diet-induced obese rat. Plosone 2013;8(1): e54617. https://doi.org/10.1371/journal.pone.0054617
  43. Neyrinck AM, Possemiers S, Druart C, Wiele TV, Backer F, Cani PD, Larondelle Y, Delzenne NM. Prebiotic Effects of Wheat Arabinoxylan Related to the Increase in Bifidobacteria, Roseburia and Bacteroides/Prevotella in Diet-Induced Obese rat. Plosone 2011;6(6):e20944. https://doi.org/10.1371/journal.pone.0020944
  44. Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS, Bae JW. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese rat. Gut 2013; 0:1-9.
  45. Cha JY, Cho YS, Kim DJ. Effect of chicory extract on the lipid metabolism and oxidative stress in rats. J. Korean Soc. Food Sci. Nutr. 2001;30:1220-6.
  46. Wang JH, Bose S, Kim GC, Hong SU, Kim JH, Kim JE, Kim HJ. Flos Lonicera Ameliorates Obesity and Associated Endotoxemia in rats through Modulation of Gut Permeability and Intestinal Microbiota. Plosone 2014;9(1):e86117. https://doi.org/10.1371/journal.pone.0086117