DOI QR코드

DOI QR Code

차전초 잎의 물 추출물이 고지방식이로 비만이 유도된 C57BL/6 생쥐에서 지질대사 단백질 발현에 미치는 영향

Effect of Plantaginis asiaticae Folium water extract on expression of lipid-related protein expression metabolism in high fat-induced obese C57BL/6 mice

  • 김소영 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 정미진 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 김유진 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 이은탁 (농업회사법인 (주)이비채) ;
  • 추성태 (농업회사법인 (주)이비채) ;
  • 김미려 (대구한의대학교 한의과대학 본초약리학교실)
  • Kim, So Young (Dept. of Herbal Pharmacology, Coll. of Korean Medicine, Daegu Haany Univ.) ;
  • Jeong, Mi Jin (Dept. of Herbal Pharmacology, Coll. of Korean Medicine, Daegu Haany Univ.) ;
  • Kim, Yoo Jin (Dept. of Herbal Pharmacology, Coll. of Korean Medicine, Daegu Haany Univ.) ;
  • Lee, Un-Tak (Ebiche co., Ltd.) ;
  • Choo, Sung-Tae (Ebiche co., Ltd.) ;
  • Kim, Mi Ryeo (Dept. of Herbal Pharmacology, Coll. of Korean Medicine, Daegu Haany Univ.)
  • 투고 : 2018.04.11
  • 심사 : 2018.05.25
  • 발행 : 2018.05.30

초록

Objective : Previous studies showed that water extract of Plantago asiatica (Plantaginis asiaticae Folium, PAF) significantly controlled in body weights, adipose tissue weights and blood lipid profiles in obese C57BL/6 mice. To investigate the mechanism of anti-obesity action of PAF, expressions of obesity-related proteins were identified such as p-AMPK and p-ACC in hypothalamus, UCP-1 in brown adipose tissue, p-AMPK, p-ACC, SREBP-1c, $PPAR{\gamma}$, HMGCR and CPT-1 in liver. Method : Five-weeks old male C57BL/6 mice were divided into 5 groups; ND (normal diet + 0.9% saline), HFD (high-fat diet + 0.9% saline), PC (high-fat diet+Garcinia cambogia 500 mg/kg), PAF 100 and 300 (high-fat diet + PAF 100 or 300 mg/kg). PAF was treated orally for 6 weeks. The protein expression of AMPK, p-AMPK, ACC, p-ACC, $PPAR{\gamma}$, SREBP-1c, HMGCR, CPT-1 and UCP-1 were identified by expression levels of proteins through western blot analysis. Result : The results showed that protein expressions on hypothalamic p-AMPK and p-ACC did not differ between the HFD and PAF groups. In addition, PAF did not affect the increase of UCP-1 in brown adipose tissue. The protein expression levels of hepatic p-AMPK, p-ACC and CPT-1 increased in PAF groups compared to HFD group. And those of $PPAR{\gamma}$, SREBP-1c and HMG-CoA decreased in PAF groups compared to HFD group. Conclusion : These results suggest that the PAF administration induce weight loss via inhibition of lipid metabolism-related protein expressions in hepatic tissues. Therefore, PAF could be used as a potent material of anti-obesity products for prevention and treatment of obesity.

키워드

참고문헌

  1. James OH, Edward LM, Holly TW. Dietary fat intake and regulation of energy balance: implications for obesity. J Nutr. 2000 ; 130 : 284S-8S. https://doi.org/10.1093/jn/130.2.284S
  2. Korea centers for disease control and prevention. Korea health statistics 2014: Korea national health and nutrition examination survey (KNHANES VI). 2016.
  3. Shin HY, Kang HT. Recent trends in the prevalence of underweight, overweight, and obesity in Korean adults: The korean national health and nutrition examination survey from 1998 to 2014. J Epidemiol. 2017 ; 27(9) : 413-9. https://doi.org/10.1016/j.je.2016.08.014
  4. Scott MG. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab. 2004 ; 89(6) : 2595-600. https://doi.org/10.1210/jc.2004-0372
  5. Tseng YH, Cypess AM, Kahn CR. Cellular bioenergetics as a target for obesity therapy. Nat Rev Drug Discov. 2010 ; 9(6) : 465-82. https://doi.org/10.1038/nrd3138
  6. Song MY, Lim SK, Wang JH, Kim HJ. The root of Atractylodes macrocephala Koidzumi prevents obesity and glucose intolerance and increases energy metabolism in mice. Int J Mol Sci. 2018 ; DIO: 10.3390/ijms19010278.
  7. Daneschvar HL, Aronson MD, Smetana GW. FDAapproved anti-obesity drugs in the United states. Am J Med. 2016 ; 129(8) : 879.e1-6. https://doi.org/10.1016/j.amjmed.2016.02.009
  8. Kang JG, Park CY. Anti-obesity drugs: a review about their effects and safety. Diabetes Metab J. 2012 ; 36 : 13-25. https://doi.org/10.4093/dmj.2012.36.1.13
  9. Yun JW. Possible anti-obesity therapeutics from nature - A review. Phytochemistry. 2010 ; 71 : 1625-41. https://doi.org/10.1016/j.phytochem.2010.07.011
  10. Saad B, Zaid H, Shanak S, Kadan S. Herbal-derived anti-obesity compounds and their action mechanisms. Anti-diabetes and Anti-obesity Medicinal Plants and Phytochemicals. 2017 ; 129-44.
  11. Ye CL, Jiang CJ. Optimization of crude polysaccharides from Plantago asiatica L. by response surface methodology. Carbohydr Polym. 2011 ; 84 : 495-502. https://doi.org/10.1016/j.carbpol.2010.12.014
  12. Ravn H, Brimer L. Struture and antibacterial activity of plantamajoside, a caffeic acid sugar ester from Plantago major subs major . Phytochemistry. 1988 ; 27(11) : 3433-7. https://doi.org/10.1016/0031-9422(88)80744-1
  13. Tundis R, Bonesi M, Menichini F, Loizzo MR, Conforti F, Statti G, Pirisi FM, Menichini F. Antioxidant and anti-cholinesterase activity of Globularia meridionalis extracts andisolatedconstituents. NatProdCommun. 2012 ; 7 : 1015-20.
  14. Danae CO, Sugeyla BG, Jaime RBB, Rola AA, Veronica RL. Anti-inflammatory activity of iridoids and verbascoside isolated from Castilleja tenuiflora. 2013 ; 18(10) : 12109-18. https://doi.org/10.3390/molecules181012109
  15. Kim SY, Jeong MJ, Kim YJ, Lee UT, Choo ST. Effect of Plantaginis asiaticae Folium water extract on body fat loss in high fat-induced obese C57BL/6 mice. Kor J Herbol. 2018 ; 33(2) : 59-68. https://doi.org/10.6116/KJH.2018.33.2.59
  16. Turel I, Hanefi H, Erten R, Oner AC, Cengiz N, Yilmaz O. Hepatoprotective and antiinflammatory activities of Plantago major L. Indian J Pharmacol. 2009 ; 41(3) : 120-4. https://doi.org/10.4103/0253-7613.55211
  17. Park SJ, Sihn EH, Kim CA. Component analysis and antioxidant activity of Plantago asiatica L. Korea J food Preserv 2011 ; 18(2) : 212-8. https://doi.org/10.11002/kjfp.2011.18.2.212
  18. Hu JL, Nie SP, Wu QM, Li C, Fu ZH, Gong J, Cui SW, Xie MY. Polysaccharide from seeds of Plantago asiatica L. affects lipid metabolism and colon microbiota of mouse. J Agric Food Chem. 2014 ; 62(1) : 229-34. https://doi.org/10.1021/jf4040942
  19. Huang DF, Xie MY, Yin JY, Nie SP, Tang YF, Xie WM, Zhou C. Immunomodulatory activity of the seeds of Plantago asiatica L. J Ethnopharmacol. 2009 ; 124(3) : 493-8. https://doi.org/10.1016/j.jep.2009.05.017
  20. Yin JY, Nie SP, Zhou C, Wan Y, Xie MY. Chemical characteristics and antioxidant activities of polysaccharide purified from the seeds of Plantago asiatica L. J Sci Food Agric. 2009 ; DOI 10.1002/jsfa.3793.
  21. Hwang JT, Kwon DY, Yoon SH. AMP-activated protein kinase: a potential target for the disease prevention by natural occurring polyphenols. N Biotechnol. 2009 ; 26 : 17-22. https://doi.org/10.1016/j.nbt.2009.03.005
  22. O'Neill HM, Holloway GP, Steinberg GR. AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: implications for obesity. Mol Cell Endocrinol. 2013 ; 366 : 135-51. https://doi.org/10.1016/j.mce.2012.06.019
  23. Hawley SA, Davison M, Wood A, Davies SP, Besi RK, Carling D, Hardie DG. Characterization of the AMP-activated protein kinase from rat liver, and identification of threonine-172 as the major site at which it phos-phorylates and activates AMPactivated protein kinase. J Biol Chem. 1996 ; 271 : 27879-87. https://doi.org/10.1074/jbc.271.44.27879
  24. Kong CS, Kim JA, Kim SK. Anti-obesity effect of sulfated glucosamine by AMPK signal pathway in 3T3-L1 adipocytes. Food Chem Toxicol. 2009 ; 47 : 2401-6. https://doi.org/10.1016/j.fct.2009.06.010
  25. Spiegelman BM, Flier JS. Obesity and the Regulation of Energy Balance. Cell. 2002 ; 104 : 531-43.
  26. Andersson U, Filipsson K, Abbott CR, Woods A, Smith K, Bloom SR, Carling D, Small CJ. AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem. 2004 ; 279 : 12005-8. https://doi.org/10.1074/jbc.C300557200
  27. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 2002 ; 415 : 339-43. https://doi.org/10.1038/415339a
  28. Hardie DG, Hawley SA, Scott JW. AMP-activated protein kinase-development of the energy sensor concept. J Physiol. 2006 ; 574 : 7-15. https://doi.org/10.1113/jphysiol.2006.108944
  29. Dietschy JM, Turley SD, Spady DK. Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J Lipid Res. 1993 ; 34 : 1637-59.
  30. McGarry JD, Brown NF. The mitochondrial carnitine palmitoyltransferase system-From concept to molecular analysis. Eur J Biochem. 1997 ; 244 : 1-14. https://doi.org/10.1111/j.1432-1033.1997.00001.x
  31. Clouet P, Henninger C, Bard J. Study of some factors controlling fatty acid oxidation in liver mitochondria of obese Zucker rats. Biochem J. 1986 ; 239 : 103-8. https://doi.org/10.1042/bj2390103
  32. Brown MS, Goldstein JL. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997 ; 89 : 331-40. https://doi.org/10.1016/S0092-8674(00)80213-5
  33. Kolehmainen M, Vidal H, Alhava E, Uusitupa MIJ. Sterol regulatory element binding protein 1c (SREBP-1c) expression in human obesity. Obes Res. 2001 ; 9(11) : 706-12. https://doi.org/10.1038/oby.2001.95
  34. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis on the liver. J Clin Invest. 2002 ; 109 : 1125-31. https://doi.org/10.1172/JCI0215593
  35. Ji C, Chan C, Kaplowitz N. Predominant role of sterol response element binding proteins (SREBP) lipogenic pathways in hepatic steatosis in the murine intragastric ethanol feeding model. J Hepatol. 2006 ; 45 : 717-24. https://doi.org/10.1016/j.jhep.2006.05.009
  36. Kalupahana NS, Claycombe KJ, Moustaid-Moussa N. (n-3) fatty acids alleviate adipose tissue inflammation and insulin resistance: mechanistic insights. Adv Nutr. 2011 ; 2(4) : 304-16. https://doi.org/10.3945/an.111.000505
  37. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013 ; 19(10) : 1252-63. https://doi.org/10.1038/nm.3361
  38. Palou A, Pico C, Bonet ML, Oliver P. The uncoupling protein, thermogenin. Int J Biochem Cell Biol. 1998 ; 30 : 7-11. https://doi.org/10.1016/S1357-2725(97)00065-4
  39. Petrovic N, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a $PPAR{\gamma}$ agonist. Am J Physiol Endocrinol Metab. 2008 ; 295 : 287-96. https://doi.org/10.1152/ajpendo.00035.2008
  40. Francesc V, Roser I, Marta G. PPARs in the control of uncoupling proteins gene expression. PPAR Res. 2007 ; DIO:10.1155/2007/74364.
  41. Festuccia WT, Blanchard PG, Richard D, Deshaies Y. Basal adrenergic tone is required for maximal stimulation of rat brown adipose tissue UCP1 expression by chronic PPAR-gamma activation. Am J Physiol Regul Integr Comp Physiol. 2010 ; DIO:10.1152/ajpregu.00821.
  42. Peng Z, Borea PA, Varani K, Wilder T, Yee H, Chiriboga L. Adenosine signaling contributes to ethanol-induced fatty liver in mice. J Clin Invest. 2009 ; 119 : 582-94. https://doi.org/10.1172/JCI37409
  43. Memon RA, Tecott LH, Nonogaki K, Beigneux A, Moser AH, Grunffld C, Feingold KR. Up-regulation of peroxisome proliferator-activated receptors (PPAR-${\alpha}$) and PPAR-${\gamma}$ messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-${\gamma}$-responsive adipose tissue-specific genes in the liver of obese diabetic mice. Endocrinology. 2000 ; 141(11) : 4021-31. https://doi.org/10.1210/endo.141.11.7771
  44. Spiegelman BM. PPAR-${\gamma}$: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998 ; 47: 507-14. https://doi.org/10.2337/diabetes.47.4.507
  45. Jones JR, Barrick C, Kim KA, Lindner B, Fujimoto Y. Deletion of $PPAR{\gamma}$ in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance. Proc Natl Acad Sci USA. 2005 ; 102 (17) : 6207-12. https://doi.org/10.1073/pnas.0306743102