한방비만학회지 (Journal of Korean Medicine for Obesity Research)

  • 제14권1호
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  • Pages.13-23
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  • 2014
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  • 1976-9334(pISSN)
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  • 2288-1522(eISSN)
한방비만학회 (The Society of Korean Medicine for obesity Research)
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RAW 264.7 세포에서 Metformin과 병행투여 시 상승효과를 나타내는 한약재의 선별 연구

Screening of Herbal Medicines for Synergistic Effects of Metformin and Herbal Extracts Combination in RAW 264.7 Cells

  • 김형구 (동국대학교 한의과대학 한방재활의학과교실) ;
  • 왕경화 (동국대학교 한의과대학 한방재활의학과교실) ;
  • 채희성 (동국대학교 약학대학 약학교실) ;
  • 진영원 (동국대학교 약학대학 약학교실) ;
  • 최한석 (동국대학교 의과대학 내분비내과교실) ;
  • 김호준 (동국대학교 한의과대학 한방재활의학과교실)
  • Kim, Hyung-Gu (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dongguk University) ;
  • Wang, Jing-Hua (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dongguk University) ;
  • Chae, Hee-Sung (Department of Pharmacy, College of Pharmacy, Dongguk University) ;
  • Chin, Young-Won (Department of Pharmacy, College of Pharmacy, Dongguk University) ;
  • Choi, Han-Seok (Department of Endocrinology Medicine, College of Medicine, Dongguk University) ;
  • Kim, Hojun (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dongguk University)
  • 투고 : 2014.05.20
  • 심사 : 2014.06.02
  • 발행 : 2014.06.30
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초록

Objectives: This study was performed to evaluate the effects of Metformin and Lonicerae Flos, Agrobacterium Rhizogenes, Coptidis Rhizoma, Atractylodis Rhizoma Alba, Houttuyniae Herba extracs combinations on hypoglycemia in RAW 264.7 cells. Methods: Expressions of Sirt1, p-adenosine monophosphate-activated kinase (p-AMPK), AMPK-alpha, peroxisome proliferator activated receptor (PPAR)-alpha, PPAR-gamma, X-box binding protein 1 (XBP-1), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were analyzed by real time polymerase chain reaction and Western blotting analysis. Results: The level of gene expression of Sirt1, p-AMPK, AMPK-alpha, PPAR-alpha and XBP-1 in relation to that of beta-actin were increased or decreased significantly with the Metformin and Lonicerae Flos, Agrobacterium Rhizogenes extracts combination groups. The level of gene expression of TNF-alpha and IL-6 were increased significantly with the Metformin and Houttuyniae Herba, Coptidis Rhizoma extracts combination groups. Conclusions: Metformin and Lonicerae Flos, Agrobacterium Rhizogenes extracts combination groups showed synergistic hypoglycemic effects by increasing AMPK and PPAR gene expression in RAW 264.7 cells.

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참고문헌

  1. Korean Diabetes Association. Textbook of diabetes. Seoul : EPUBLIC. 2006 : 2-4.
  2. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007 ; 132 : 2169-80. https://doi.org/10.1053/j.gastro.2007.03.059
  3. Fineman MS, Bicsak TA, Shen LZ, Taylor K, Gaines E, Varns A, et al. Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care. 2003 ; 26 : 2370-7. https://doi.org/10.2337/diacare.26.8.2370
  4. Tosi F, Muggeo M, Brun E, Spiazzi G, Perobelli L, Zanolin E, et al. Combination treatment with metformin and glibenclamide versus single-drug therapies in type 2 diabetes mellitus: a randomized, double-blind, comparative study. Metabolism. 2003 ; 52 : 862-7. https://doi.org/10.1016/S0026-0495(03)00101-X
  5. Oudjeriouat N, Moreau Y, Santimone M, Svensson B, Marchis Mouren G, Desseaux V. On the mechanism of alpha-amylase. Eur J Biochem. 2003 ; 270 : 3871-9. https://doi.org/10.1046/j.1432-1033.2003.03733.x
  6. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 ; 108 : 1167-74. https://doi.org/10.1172/JCI13505
  7. Huang NL, Chiang SH, Hsueh CH, Liang YJ, Chen YJ, Lai LP. Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation. Int J Cardiol. 2009 ; 134 : 169-75. https://doi.org/10.1016/j.ijcard.2008.04.010
  8. Waisundara VY, Huang M, Hsu A, Huang D, Tan BK. Characterization of the anti-diabetic and antioxidant effects of rehmannia glutinosa in streptozotocin-induced diabetic Wistar rats. Am J Chin Med. 2008 ; 36(6) : 1083-104. https://doi.org/10.1142/S0192415X08006594
  9. Waisundara VY, Hsu A, Huang D, Tan BK. Scutellaria baicalensis enhances the anti-diabetic activity of metformin in streptozotocin-induced diabetic Wistar rats. Am J Chin Med. 2008 ; 36(3) : 517-40. https://doi.org/10.1142/S0192415X08005953
  10. Professors of herbology in colleges of oriental medicine. Herbology. Seoul:Younglimsa. 2004:581-3.
  11. Han HK, Je HS, Kim GH. Effects of cirsium japonicum powder on plasma glucose and lipid level in streptozotocin induced daibetic rats. Korean J Food Sci Technol. 2010;42:343-9.
  12. Son DW, Kim DG, Lee SJ. Effect of natural functional mixture on the descent of blood glucose level in streptozotocin-induced diabetic (typeI) rats(II). Korean J Culin Res. 2011;17: 238-47.
  13. Han YK, Park YK. Effect of Atractylodis Rhizoma Alba water extract on streptozotocin-induced diabetes in rats. Korean J Herbol. 2011 ; 26(4) : 23-30.
  14. Jun YE. Partial purification of houttuynia cordata thunb extract and characterization of its immunological activities in human system. MS Thesis. Seoul: Seoul University. 1997 : 1-43.
  15. Kang JM. Identification of volatile essential oil, and flavor characterization and antibacterial effect of fractions from Houttuynia cordata Thunb -II. Flavor characterization and antibacterial effect of fraction from Houttuynia cordata Thunb by Prep-HPLC-. MS Thesis. Busan: Pukyong Natioal University. 1997 : 1-34.
  16. Gil YS. An experimental study on the effects of Houttuynia cordata Thunb and sanggukeum on immune function. MS Thesis. Seoul: Kyung Hee University. 1990 : 1-56.
  17. Lee JW. Experimental study on the preventive effects of Houttuyniae herba on hyperlipidemia. MS Thesis. Seoul: Kyung Hee University. 1995 : 1-27.
  18. Lee HJ, Kim KJ. The effects of Houttuyniae Herba on the mast cell-mediated inflammatory responses. J Korean Orient Med Ophthalmol Otolaryngol Dermatol. 2009 ; 22(2) : 60-73.
  19. World Health Organization. Lead Environmental health criteria 3. Geneva : WHO. 1997 : 160.
  20. Gok JK, Kim JJ, No YL, Lee SH, Jung SY, Jung HJ, Jung SK. Experimental Research on the Effect of Haeyeol-tang. J Korean Orient Intern Med. 2007 ; 28(4) : 671-80.
  21. Huang Y, Tsang SY, Yao X, Chen ZY. Biological properties of baicalein in cardiovascular system. Curr Drug Targets Cardiovasc Haematol Disord. 2005 ; 5 : 177-84. https://doi.org/10.2174/1568006043586206
  22. Jung HS, Kim MH, Gwak NG, Im YS, Lee KY, Sohn Y, et al. M. Antiallergic effects of Scutellaria baicalensis on inflammation in vivo and in vitro. J Ethnopharmacol. 2012 ; 141 : 345-9. https://doi.org/10.1016/j.jep.2012.02.044
  23. Lu Y, Joerger R, Wu C. Study of the chemical composition and antimicrobial activities of ethanolic extracts from roots of Scutellaria baicalensis Georgi. J Agric Food Chem. 2011 ; 59 : 10934-42. https://doi.org/10.1021/jf202741x
  24. Waisundara VY, Hsu A, Huang D, Tan BK. Scutellaria baicalensis enhances the anti-diabetic activity of metformin in streptozotocin-induced diabetic Wistar rats. Am J Chin Med 2008 ; 36 : 517-40. https://doi.org/10.1142/S0192415X08005953
  25. Lee JS, Park HG, Woo ER, Lee EJ, An DG, Yoon WS, et al. A study on the extraction efficiency of berberine in coptodis rhizoma. J Analytical Sci Technol. 1997 ; 10(2) : 83-90.
  26. Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, et al. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 2002 ; 51(7) : 2074-81. https://doi.org/10.2337/diabetes.51.7.2074
  27. Kola B, Grossman AB, Korbonits M. The role of AMP-activated protein kinase in obesity. Front Horm Res. 2008 ; 36 : 198.
  28. Janovska A, Hatzinikolas G, Staikopoulos V, McInerney J, Mano M, Wittert GA. AMPK and ACC phosphorylation: effect of leptin, muscle fibre type and obesity. Mol Cell Endocrinol. 2007 ; 1 : 284.
  29. Landree LE, Hanlon AL, Strong DW, Rumbaugh G, Miller IM, Thupari JN, et al. C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism. J Biol Chem. 2004 ; 3817 : 279.
  30. Guo W, Huang N, Cai J, Xie W, Hamilton JA. Fatty acid transport and metabolism in HepG2 cells. Am J Physiol Gastrointest Liver Physiol. 2006 ; 290(3) : 528-34. https://doi.org/10.1152/ajpgi.00386.2005
  31. Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell. 1992 ; 68(5) : 879-87. https://doi.org/10.1016/0092-8674(92)90031-7
  32. Rossen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, et al. PPAR gamma is required for the differentiatio of adipose tissue in vivo and in vitro. Mol Cell. 1999 ; 4 : 611-7. https://doi.org/10.1016/S1097-2765(00)80211-7
  33. Rossen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, et al. PPAR gamma is required for the differentiatio of adipose tissue in vivo and in vitro. Mol Cell. 1999 ; 4 : 611-7. https://doi.org/10.1016/S1097-2765(00)80211-7
  34. Park SW, Zhou YJ, Lee J, Lu A, Sun C, Chung J, et al. The regulatory subunits of pi3k, p85$\alpha$ and p85$\beta$, interact with XBP-1 and increase its nuclear translocation. Nat Med Apir. 2010 ; 16(4) : 429-37. https://doi.org/10.1038/nm.2099
  35. Feldmann M, Saklatvala J. Proinflammatory cytokines. In: Oppenheim JJ, Feldman M, editors. Cytokine reference. New York : Academic Press. 2001 : 291-305.
  36. Vila-del Sol V, Fresno M. Involvement of TNF and NF-kB in the transcriptional control of cyclooxygenase-2 expression by IFN-$\gamma$ in macrophages. J Immunol. 2005 ; 174 : 2825-33. https://doi.org/10.4049/jimmunol.174.5.2825
  37. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Ann Rev Phisiol. 2010 ; 72 : 219-46. https://doi.org/10.1146/annurev-physiol-021909-135846
  38. JI ZZ, Dai Z, XU YC. Anew tumor necrosis factor (TNF)-$\alpha$ regulator, lipopolysaccharides-induced TNF-$\alpha$ factor, is associated with obesity and insulin resistance. Chin Med J. 2011 ; 124(2) : 177-82.
  39. Hashizume M, Mihara M. Atherogenic effects of TNF-$\alpha$ and IL-6 via upregulation of scavenger receptors. Cytokine. 2012 ; 58 : 424-30. https://doi.org/10.1016/j.cyto.2012.02.010
  40. Jung IJ. The role of plasminogen activator inhibitor-1 in the regulation of adipocyte function. MS Thesis. Seoul: Ewha Womans University. 2013 : 1-90.

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