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Methanol extract of Lespedeza maximowiczii var. tricolor Nakai improves glucose metabolism through PPARγ agonist and insulin-mimetic effect in 3T3-L1 adipocytes and db/db mice

삼색싸리 메탄올 추출물의 3T3-L1지방세포와 db/db 마우스에서의 PPARγ 작용제와 인슐린 유사효과를 통한 혈당조절 개선효과

  • Park, Chul-Min (Environmental Technology Research Institute, Seoul National University of Science and Technology) ;
  • Kim, Hui (Dept. of Oriental Medicine Resources and Institute of Korean Medicine Industry, Mokpo National University) ;
  • Rhyu, Dong-Young (Dept. of Oriental Medicine Resources and Institute of Korean Medicine Industry, Mokpo National University)
  • Received : 2019.09.17
  • Accepted : 2019.11.11
  • Published : 2019.12.31

Abstract

The aim of this study is to investigate the effect of Lespedeza maximowiczii var. tricolor Nakai (LMTN) on glucose metabolism. LMTN extract significantly enhanced the glucose uptake and lipid accumulation in 3T3-L1 adipocytes compared with control. Also, LMTN extract in 3T3-L1 adipocytes significantly increased the protein expression of peroxisome proliferator-activated receptor (PPAR)γ, insulin receptor substrate-1, and glucose transporter (GLUT)4. The regulatory effect on glucose uptake or insulin signal transduction of LMTM extract was lower than troglitazone or pinitol such as the positive control, but increased PPARγ activation. Additionally, LMTM extract has an insulin-mimetic effect. In db/db mice, LMTN extract (250 mg/kg BW) significantly reduced water and food intake, blood glucose, and level of plasma triglyceride and total cholesterol. Furthermore, the expression of PPARã and GLUT4 mRNA in adipose or muscle tissue effectively was increased by oral treatment of LMTN extract. Thus, our results suggest that LMTN extract improves the glucose metabolism through PPARγ and insulin-mimetic effect in 3T3-L1 adipocytes and db/db mice.

이 연구의 목적은 당 대사에 대한 삼색싸리(Lespedeza maximowiczii var. tricolor Nakai; LMTN)의 효과를 조사하는 것이다. LMTN 추출물은 대조군과 비교하여 3T3-L1 지방 세포에서 당 섭취능 및 지질축적을 유의하게 향상시켰다. 또한, 3T3-L1 지방 세포에서 LMTN 추출물은 퍼옥시좀 증식제 활성화 수용체(PPAR)γ, 인슐린수용체기질-1 (IRS-1) 및 포도당수송체(GLUT)4의 단백질 발현을 유의하게 증가시켰다. LMTM 추출물의 당 섭취능 또는 인슐린 신호 전달계의 조절 효과는 양성 대조물질인 트로글리타존 또는 피니톨보다 낮았지만 PPARγ 단백 활성화는 증가하였다. 또한, LMTM 추출물은 인슐린 유사효과를 나타냈다. db/db 마우스에서, LMTN 추출물(250 mg/kg BW)은 물과 식이 섭취량, 혈당, 중성지방과 총 콜레스테롤 함량을 유의적으로 감소시켰다. 더불어 지방과 근육조직에서의 PPARγ 및 GLUT4 mRNA의 발현도 LMTN 추출물 투여군에서 유의적으로 증가되었다. 따라서, 본 연구의 결과는 LMTN 추출물이 3T3-L1 지방세포 및 db/db 마우스에서 PPARγ 및 인슐린 유사효과를 통해 당 대사를 조절하는 것으로 밝혀졌다.

Keywords

References

  1. Mokdad AH, Ford ES, Bowman BA, Nelson DE, Engelgau MM, Vinicor F, Marks JS (2000) Diabetes trends in the U.S.: 1990-1998. Diabetes Care 23: 1278-1283 https://doi.org/10.2337/diacare.23.9.1278
  2. Santoso T (2006) Prevention of cardiovascular disease in diabetes mellitus: by stressing the CARDS study. Acta Med Indones 38: 97-102
  3. Roy Taylor (2012) Insulin resistance and type 2 diabetes. Diabetes 61: 778-779 https://doi.org/10.2337/db12-0073
  4. Taniguchi CM, Emanuelli B, Kahn CR (2006) Critical nodes in signaling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7: 85-96 https://doi.org/10.1038/nrm1837
  5. Frojdo S, Vidal H, Pirola L (2009) Alterations of insulin signaling in type 2 diabetes: a review of the current evidence from humans. Biochim Biophys Acta 1792: 83-92 https://doi.org/10.1016/j.bbadis.2008.10.019
  6. Shin MJ, Park MJ, Youn MS, Lee YS, Nam MS, Park IS, Jeong YH (2006) Effects of silk protein hydrolysates on blood glucose in C57BL/KsJ db/db mice. J Korean Soc Food Sci Nutr 35: 1166-1171 https://doi.org/10.3746/JKFN.2006.35.9.1166
  7. Choi H J, Kim SW (2006) Therapeutic roles of PPAR-${\gamma}$ agonists. J Korean Acad Fam Med 27: 599-606
  8. Lee SH, Lee JK, Kim IH (2012) Trends and perspectives in the development of antidiabetic drugs for type 2 diabetes mellitus. Korean J Microbiol Biotechnol 40: 180-185 https://doi.org/10.4014/kjmb.1205.05012
  9. Kwon HS (2012) Mechanism and efficacy of new anti-diabetic medications. J Korean Diabetes 13: 167-171 https://doi.org/10.4093/jkd.2012.13.4.167
  10. Nissen SE, Wolski K (2007) Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356: 2457-2471 https://doi.org/10.1056/NEJMoa072761
  11. Nasri H, Rafieian-Kopaei M (2014) Metformin: Current knowledge. J Res Med Sci 19: 658-664
  12. Atta-Ur-Rahman, Zaman K (1989) Medicinal plants with hypoglycemic activity. J Ethnopharmacol 26: 1-55 https://doi.org/10.1016/0378-8741(89)90112-8
  13. Perseghin G, Lattuada G, Danna M, Sereni LP, Maffi P, De Cobelli F, Battezzati A, Secchi A, Del Maschio A, Luzi L (2003) Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes. Am J Physiol Endocrinol Metab 285: E1174-1181 https://doi.org/10.1152/ajpendo.00279.2003
  14. Yao ZY, Kan FL, Wang ET, Wei GH, Chen WX (2002) Characterization of rhizobia that nodulate legume species of the genus Lespedeza and description of Bradyrhizobium yuanmingense sp. nov. Int J Syst Evol Microbiol 52: 2219-2230 https://doi.org/10.1099/ijs.0.01408-0
  15. Yoo BK (2015) Effect of Lespedeza bicolor water extract for the management of type 2 diabetes Mellitus. Korean J Community Pharm 1: 39-43
  16. Nemoto T, Ohashi H (1993) Seedling morphology of Lespedeza (Leguminosae). J Plant Res 106: 121-128 https://doi.org/10.1007/bf02344415
  17. Kim CK (1993) Compositions of fatty acid, free amino acid and total amino acid of Lespedeza$\times$chiisanensis T. LEE. J Korean Soc Food Sci Nutr 22: 586-591
  18. Heo DY, Kim YM, Lee J, Park SH, Kim J, Park HM, Lee CH (2014) Desmodianone H and uncinanone B, potential tyrosinase inhibitors obtained from Lespedeza maximowiczii by using bioactivity-guided isolation. Biosci Biotechnol Biochem 78: 943-945 https://doi.org/10.1080/09168451.2014.905180
  19. Kim Nk, Park HM, Lee J, Ku KM, Lee CH (2015) Seasonal Variations of Metabolome and Tyrosinase Inhibitory Activity of Lespedeza maximowiczii during Growth Periods. J Agric Food Chem 63: 8631-8639 https://doi.org/10.1021/acs.jafc.5b03566
  20. Lee YS, Joo EY, Kim NW (2005) Analysis on the components in stem of the Lespedeza bicolor. J Korean Soc Food Sci Nutr 34: 1246-1250 https://doi.org/10.3746/JKFN.2005.34.8.1246
  21. Tan L, Zhang XF, Yan BZ, Shi HM, Du LB, Zhang YZ, Wang LF, Tang YL, Liu Y (2007) A novel flavonoid from Lespedeza virgata (Thunb.) DC.: structural elucidation and antioxidative activity. Bioorg Med Chem Lett 17: 6311-6315 https://doi.org/10.1016/j.bmcl.2007.09.003
  22. Mori-Hongo M, Yamaguchi H, Warashina T, Miyase T (2009) Melanin synthesis inhibitors from Lespedeza cyrtobotrya. J Nat Prod 72: 63-71 https://doi.org/10.1021/np800535g
  23. Kim SM, Jung YJ, Pan CH, Um BH (2010) Antioxidant activity of methanol extracts from the genus Lespedeza. J Korean Soc Food Sci Nutr 39: 769-775 https://doi.org/10.3746/JKFN.2010.39.5.769
  24. Lee YS, Joo EY, Kim NW (2006) Polyphenol contents and physiological activity of the Lespedeza bicolor extracts. Korean J Food Preserv 13: 616-622
  25. Lee YS, Joo EY, Kim NW (2005) Antioxidant activity of extracts from the Lespedeza bicolor. Korean J Food Preserv 12: 75-79
  26. Lee A, Kim BN, Zhoh CK, Shin GH (2006) Studies on the antioxidantive and antimicrobial effects of Lespedeza bicolor extracts. J Korean Soc of Esthe Cosmec 1: 109-120
  27. Ryu IS, Lee SJ, Lee SW, Mun YJ, Woo WH, Kim YM, Lee JC, Lim KS (2007) Dermal bioactive properties of the ethanol extract from flowers of Lespedeza bicolor. J Korean Med Ophthalmol Otolaryngol Dermatol 20: 1-9
  28. Baek SH, Kim JH, Kim DH, Lee CY, Kim JY, Chung DK, Lee CH (2008) Inhibitory effect of dalbergioidin isolated from the trunk of Lespedeza cyrtobotrya on melanin biosynthesis. J Microbiol Biotechnol 18: 874-879
  29. Maya MH, Hiroyuki T, Takayuki K, Makoto K, Yu I, Toshio M (2009) Melanin synthesis inhibitors from Lespedeza floribunda. J Nat Prod 72: 194-203 https://doi.org/10.1021/np800395j
  30. Kwon DJ, Bae YS (2009) Flavonoids from the aerial parts of Lespedeza cuneata. Biochem Syst Ecol 37: 46-48 https://doi.org/10.1016/j.bse.2008.11.014
  31. Kim MS, Sharma BR, Rhyu DY (2016). Beneficial effect of Lespedeza cuneata (G. Don) water extract on streptozotocin-induced type 1 diabetes and cytokine-induced beta-cell damage. Nat Prod Sci 22: 175-179 https://doi.org/10.20307/nps.2016.22.3.175
  32. Sharma BR, Rhyu DY (2015). Lespedeza davurica (Lax.) Schindl. extract protects against cytokine-induced ${\beta}$-cell damage and streptozotocininduced diabetes. Biomed Res Int 2015: 169256 https://doi.org/10.1155/2015/169256
  33. Rubin CS, Hirsch A, Fung C, Rosen OM (1978) Development of hormone receptors and hormonal responsiveness in vitro. Insulin receptors and insulin sensitivity in the preadipocyte and adipocyte forms of 3T3-L1 cells. J Biol Chem 253: 7570-7578 https://doi.org/10.1016/S0021-9258(17)34541-6
  34. Inoue G, Cheatham B, Emkey R, Kahn CR (1998) Dynamics of insulin signaling in 3T3-L1 adipocytes. Differential compartmentalization and trafficking of insulin receptor substrate (IRS)-1 and IRS-2. J Biol Chem 273: 11548-11555 https://doi.org/10.1074/jbc.273.19.11548
  35. Ko BS, Kim HK, Park SM (2002) Natural products, organic chemistry: Insulin sensitizing and insulin-like effects of water extracts from Kalopanax pictus NAKAI in 3T3-L1 adipocyte. J Korean Soc Agric Chem Biotechnol 45: 42-46
  36. Choi SS, Cha BY, Iida K, Lee YS, Yonezawa T, Teruya T, Nagai K, Woo JT (2011) Artepillin C, as a PPARa ligand, enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells. Biochem Pharmacol 81: 925-933 https://doi.org/10.1016/j.bcp.2011.01.002
  37. Kim DY, Park KK, Lee SK, Lee SE, Hwang JK (2011). Cornus kousa F.Buerger ex Miquel increases glucose uptake through activation of peroxisome proliferator-activated receptor and insulin sensitization. J Ethnopharmacol 133: 803-809 https://doi.org/10.1016/j.jep.2010.11.007
  38. Guest PC, Rahmoune H (2019) Characterization of the db/db Mouse Model of Type 2 Diabetes. Methods Mol Biol 1916: 195-201 https://doi.org/10.1007/978-1-4939-8994-2_18
  39. Min KH, Kim HJ, Jeon YJ, Han JS (2011) Ishige okamurae ameliorates hyperglycemia and insulin resistance in C57BL/KsJ-db/db mice. Diabetes Res Clin Pract 93: 70-76 https://doi.org/10.1016/j.diabres.2011.03.018
  40. Yeo JY, Kang YM, Cho SI, Jung MH (2011) Effects of a multi-herbal extract on type 2 diabetes. Chin Med 6: 10 https://doi.org/10.1186/1749-8546-6-10
  41. Han KL, Choi JS, Lee JY, Song J, Joe MK, Jung MH, Hwang JK (2008) Therapeutic potential of peroxisome proliferators--activated receptoralpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetes. Diabetes 57: 737-745 https://doi.org/10.2337/db07-0972
  42. Mooradian AD (2009) Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab 5: 150-159 https://doi.org/10.1038/ncpendmet1066