Korean Journal of Medicinal Crop Science (한국약용작물학회지)

The Korean Society of Medicinal Crop Science (한국약용작물학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-obesity Effect of the Flavonoid Rich Fraction from Mulberry Leaf Extract

뽕잎 추출물 기원 Flavonoid Rich Fraction의 항비만효과

  • Go, Eun Ji (Department of Bio-Health Convergence, Kangwon National University) ;
  • Ryu, Byung Ryeol (Department of Bio-Health Convergence, Kangwon National University) ;
  • Yang, Su Jin (Department of Herbal Medicine Resource, Kangwon National University) ;
  • Baek, Jong Suep (Department of Bio-Health Convergence, Kangwon National University) ;
  • Ryu, Su Ji (Department of Bio-Health Convergence, Kangwon National University) ;
  • Kim, Hyun Bok (National Institute of Agricultural Sciences, RDA) ;
  • Lim, Jung Dae (Department of Bio-Health Convergence, Kangwon National University)
  • 고은지 (강원대학교 바이오헬스융합학과) ;
  • 류병렬 (강원대학교 바이오헬스융합학과) ;
  • 양수진 (강원대학교 생약자원개발학과) ;
  • 백종섭 (강원대학교 바이오헬스융합학과) ;
  • 유수지 (강원대학교 바이오헬스융합학과) ;
  • 김현복 (농촌진흥청 국립농업과학원) ;
  • 임정대 (강원대학교 바이오헬스융합학과)
  • Received : 2020.10.16
  • Accepted : 2020.12.07
  • Published : 2020.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: This study investigated the anti-obesity effect of the flavonoid rich fraction (FRF) and its constituent, rutin obtained from the leaf of Morus alba L., on the lipid accumulation mechanism in 3T3-L1 adipocyte and C57BL/6 mouse models. Methods and Results: In Oil Red O staining, FRF (1,000 ㎍/㎖) treatments showed inhibition rate of 35.39% in lipid accumulation compared to that in the control. AdipoRedTM assay indicated that the triglyceride content in 3T3-L1 adipocytes treated with FRF (1,000 ㎍/㎖) was reduced to 23.22%, and free glycerol content was increased to 106.04% that of the control. FRF and its major constituent, rutin affected mRNA gene expression. Rutin contributed to the inhibition of Sterol regulatory element binding protein-1c (SREBP-1c) gene expression, and inhibited the transcription factors SREBP-1c, peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). In addition, the effect of FRF administration on obesity development in C57BL/6 mice fed high-fat diet (HFD) was investigated. FRF suppressed weight gain, and reduced liver triglyceride and leptin secretion. FRF exerted potential anti-inflammatory effects by improving insulin resistance and adiponectin levels, and could thus be used to help counteract obesity. The mRNA expressions of PPAR-γ, FAS, ACC, and CPT-1 were determined in liver tissue. Quantitative real-time PCR analysis was also performed to evaluate the expression of IL-1β, IL-6, and TNF-α in epididymal adipose tissue. Compared to the control group, mice fed the HFD showed the up-regulation in PPAR-γ, FAS, IL-6, and TNF-α genes, and down-regulation in CPT1 gene expression. FRF treatement markedly reduced the expression of PPAR-γ, FAS, IL-6, and TNF-α compared to those in HFD control, whereas increased the expression level of CPT1. Conclusions: These results suggest that the FRF and its major active constituent, rutin, can be used as effective anti-obesity agents.

Keywords

Acknowledgement

본 연구는 농촌진흥청 연구사업(과제번호: PJ013606032020)의 지원에 의해 이루어진 결과로 이에 감사드립니다.

References

  1. Ahn J, Lee H, Kim S, Park J and Ha T. (2008). The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochemical and Biophysical Research Communications. 373:545-549. https://doi.org/10.1016/j.bbrc.2008.06.077
  2. Ali AT, Hochfeld WE, Myburgh R and Pepper MS. (2013). Adipocyte and adipogenesis. European Journal of Cell Biology. 92:229-236. https://doi.org/10.1016/j.ejcb.2013.06.001
  3. Alihaid G, Grimaldi P and Negrel R. (1992). Cellular and molecular aspects of adipose tissue development. Annual Review of Nutrition. 12:207-233. https://doi.org/10.1146/annurev.nu.12.070192.001231
  4. Ann JY, Eo H and Lim Y. (2015). Mulberry leaves(Morus alba L.) ameliorate obesity-induced hepatic lipogenesis, fibrosis, and oxidative stress in high fat diet-fed mice. Genes Nutrition. 10:1-13. https://doi.org/10.1007/s12263-014-0449-8
  5. Arcri DP, Bartchewsky W, dos Santos TW, Oliveira KA, Funck A, Pedrazzoli J, de Souza MF, Saad MJ, Bastos DH, Gambero A, Carvalho Pde O and Ribeiro ML. (2009). Antiobesity effects of yerba mateextract(Ilex paraguariensis) in high-fat diet-induced obese mice. Obesity. 17:2127-2133. https://doi.org/10.1038/oby.2009.158
  6. Attila H, Katalin V, Danko B, Zoltan K, Edit W, Anasztasia H, Istvan Z and Yusty-Jouan H. (2013). In vitro anti-diabetic activity and chemical characterization of an apolar fraction of Morus alba leaf water extract. Phytotherapy Research. 27:847-851. https://doi.org/10.1002/ptr.4803
  7. Bartchewsky W, Tanila W, Oliveira K, Deoliveira CC, Gotardo ÉM, Pedrazzoli J Jr, Gambero A, Ferraz LF, Carvalho Pde O and Ribeiro ML. (2011). Anti-inflammatory effects of yerba mate extract(Ilex paraguariensis) ameliorate insulin resistance in mice with high fat dietinduced obesity. Molecular and Cellular Endocrinology. 335:110-115. https://doi.org/10.1016/j.mce.2011.01.003
  8. Boney AM, Moats-ataats BM, Stiles AD and Dercole AJ. (1994). Expression of insulin-like growth factor-I(IGF-1) and IGF-binding proteins during adipogenesis. Endocrinology. 135: 1863-1868. https://doi.org/10.1210/en.135.5.1863
  9. Cannon B and Nedergaard J. (2004). Brownadipose tissue: Function and physiological significance. Physiological Rev. 84:277-359. https://doi.org/10.1152/physrev.00015.2003
  10. Choi I, Park Y, Choi H and Lee EH. (2006). Anti-adipogenic activity of rutin in 3T3-L1 cells and mice fed with high-fat diet. BioFactors. 26:273-281. https://doi.org/10.1002/biof.5520260405
  11. Emamat H, Nouri M, Foroughi F, Rismanchi M, Eini-Zinab H and Hekmatdoost A. (2016). An accessible and pragmatic experimental model of nonalcoholic fatty liver disease. Middle East Journal of Digestive Diseases. 8:109-115. https://doi.org/10.15171/mejdd.2016.15
  12. Fu Y, Luo N, Klein RL and Garvey WT. (2005). Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. Journal of Lipid Research. 46:1369-1379. https://doi.org/10.1194/jlr.M400373-JLR200
  13. Han MH, Kim HJ, Jeong JW, Park C, Kim BW and Choi YH. (2018). Inhibition of adipocyte differentiation by anthocyanins isolated from the fruit of Vitis coignetiae Pulliat is associated with the activation of AMPK signaling pathway. Toxicological Research. 34:13-21. https://doi.org/10.5487/TR.2018.34.1.013
  14. Hwang JY, Wu YX, Hwang DI, Bae SJ and Kim T. (2014). Anti-obesity effect of Polygala tenuifolia. Korean Journal of Food Preservation. 21:97-106. https://doi.org/10.11002/KJFP.2014.21.1.97
  15. Jayarathne S, Koboziev I, Park OH, Oldewage-Theron W, Shen CL and Moustaid-Moussa N. (2017). Anti-inflammatory and anti-obesity properties of food bioactive components: Effects on adipose tissue. Preventive Nutrition and Food Science. 22:251-262. https://doi.org/10.3746/pnf.2017.22.4.251
  16. Kajimura S, Spiegelman BM and Seale P. (2015). Brown and beige fat: Physiological roles beyond heat generation. Cell Metabolism. 22:546-559. https://doi.org/10.1016/j.cmet.2015.09.007
  17. Khalilpourfarshbafi M, Gholami K, Murugan DD, Sattar MZA and Abdullah NA. (2019). Differential effects of dietary flavonoids on adipogenesis. European Journal of Nutrition. 58:5-25. https://doi.org/10.1007/s00394-018-1663-8
  18. Kim GS, Park HJ, Woo JH, Kim MK, Koh PO, Min W, Ko YG, Kim CH, Won CK and Cho JH. (2012). Citrus aurantium flavonoids inhibit adipogenesis through the Akt signaling pathway in 3T3-L1 cells. BMC Complement. Alternative Medicine. 12:31.
  19. Kim HB, Seo SD, Koo HY, Seok YS, Kim SL and Sung GB. (2013). Quantitative analysis of 1-deoxynojirimycin in mulberry leaves. Journal of Sericultural and Entomological Science. 51:20-29. https://doi.org/10.7852/JSES.2013.51.1.20
  20. Kim JE and Chen J. (2004). Regulation of peroxisome proliferatoractivated receptor-γ activity by mammalian target of rapamycin and amino acids in adipogenesis. Diabetes. 53:2748-2756. https://doi.org/10.2337/diabetes.53.11.2748
  21. Kim KH. (1997). Regulation of mammalian acetyl-coenzyme a carboxylase. Annual Review of Nutrition. 17:77-99. https://doi.org/10.1146/annurev.nutr.17.1.77
  22. Kim SK, Kim SY, Kim HJ and Kim AJ. (2001). The effect of mulberry-leaf extract on the body fat accumulation in obese fa/fa male zucker rats. Journal of the Korean Society of Food Science and Nutrition. 30:516-520.
  23. Lefterova MI and Lazar MA. (2009). New developments in adipogenesis. Trends in Endocrinology and Metabolism. 20:107-114. https://doi.org/10.1016/j.tem.2008.11.005
  24. Lefterova MI, Zhang Y, Steger DJ, Schupp M, Schug J, Cristancho A, Feng D, Zhuo D, Stoeckert CJ, Liu XS and Lazar MA. (2008). PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes and Development. 22:2941-2952. https://doi.org/10.1101/gad.1709008
  25. Lowell BB and Spiegelman BM. (2000) Towards a molecular understanding of adaptive thermogenesis. Nature. 404:652-660. https://doi.org/10.1038/35007527
  26. Maratos-Flier E. (2008). The long reach of leptin. Nature Medicine. 14:604-606. https://doi.org/10.1038/nm0608-604
  27. Mattews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF and Turner RC. (1985). Hemeostasis model assessment: Insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetolodia. 282: 412-419.
  28. Prince PS and Kamalakkannan N. (2006). Rutin improves glucose homeostasis in streptozotocin diabetic tissues by altering glycolytic and gluconeogenic enzymes. Journal of Biochemical and Molecular Toxicology. 20:96-102. https://doi.org/10.1002/jbt.20117
  29. Rosenbaum M and Leibel RL. (1999). clinical review 107: Role of gonadal steroids in the sexual dimorphisms in body composition and circulating concentrations of leptin. Journal of Clinical Endocrinology and Metabolism. 84:1784-1789. https://doi.org/10.1210/jcem.84.6.5787
  30. Rucker D, Padwal R, Li SK, Curioni C and Lau DC. (2007). Long term pharmacotherapy for obesity and overweight: Updated metanalysis. British Medical Journal. 335:1194-1199.
  31. Samuel Wu YH, Chiu CH, Yang DJ, Lin YL, Tseng JK and Chen YC. (2013). Inhibitory effects of litchi(Litchi chinensis Sonn.) flower-water extracts on lipase activity and diet-induced obesity. Journal of Functional Foods. 5:923-929. https://doi.org/10.1016/j.jff.2013.02.002
  32. Schmid B, Rippmann JF, Tadayyon M and Hamilton BS. (2005). Inhibition of fatty acid synthase prevents preadipocyte differentiation. Biochemical and Biophysical Research Communications. 328:1073-1082. https://doi.org/10.1016/j.bbrc.2005.01.067
  33. Skurk T, Alberti-Huber C, Herder C and Hauner H. (2007). Relationship between adipocyte size and adipokine expression and secretion. Journal of Clinical Endocrinology and Metabolism. 92:1023-1033. https://doi.org/10.1210/jc.2006-1055
  34. Song Y, Park HJ, Kang SN, Jang SH, Lee SJ, Ko YG, Kim GS and Cho JH. (2013). Blueberry peel extracts inhibit adipogenesis in 3T3-L1 cells and reduce high-fat diet-induced obesity. PLoS ONE. 8:e69925. https://doi.org/10.1371/journal.pone.0069925
  35. Spiegelman BM and Flier JS. (1996). Adipogenesis and obesity: Rounding out the big picture. Cell. 87:377-389. https://doi.org/10.1016/S0092-8674(00)81359-8
  36. Tao Y and Zhang Y. (2013). Rapid screening and identification of glucosidase inhibitors from mulberry leaves using enzyme immobilized magnetic beads coupled with HPLC/MS and NMR. Biomed Chromatography. 27:148e155. https://doi.org/10.1002/bmc.2761
  37. Torgerson JS, Hauptman J, Boldrin MN and Sjostrom L. (2004). XENical in the prevention of diabetes in obese subjects(XENDOS) study: A randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 27:155-161. https://doi.org/10.2337/diacare.27.1.155
  38. Tsuda M, Shigemoto-Mogami Y, Koizumi S, Mizokoshi A, Kohsaka S, Salter MW and Inoue K. (2004). P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature. 424:778-783. https://doi.org/10.1038/nature01786
  39. Van der Wier B, Koek GH, Bast A and Haenen GRMM. (2015). The potential of flavonoids in the treatment of nonalcoholic fatty liver disease. Critical Reviews in Food Science and Nutrition. 57:834-855.
  40. Wongs-Aree C, Giusti M and Schwartz S. (2006). Anthocyanins derived only from delphinidin in the blue petals of Clitoria ternatea. In Proceedings of the IV International Conference on Managing Quality in Chains-The Integrated View on Fruits and Vegetables Quality, Bangkok, Thailand. 30:437-442.
  41. Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ and Spiegelman BM. (1999). Cross-regulation of C/EBPα and PPARγ controls the transcriptional pathway of adipogenesis and insulin sensitivity. Molecular Cell. 3:151-158. https://doi.org/10.1016/S1097-2765(00)80306-8
  42. You Y, Yuan X, Lee HJ, Huang W, Jin W and Zhan J. (2015). Mulberry and mulberry wine extract increase the number of mitochondria during brown adipogenesis. Food and Function. 6:401-408. https://doi.org/10.1039/c4fo00719k