Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-diabetic effect of mulberry leaf extract fermented with Lactobacillus plantarum

Lactobacillus plantarum으로 발효한 뽕잎 추출물의 항당뇨 효과

  • Choi, Jisu (Department of Food Science and Biotechnology, Gachon University) ;
  • Lee, Sulhee (Department of Food Science and Biotechnology, Gachon University) ;
  • Park, Young-Seo (Department of Food Science and Biotechnology, Gachon University)
  • 최지수 (가천대학교 식품생물공학과) ;
  • 이설희 (가천대학교 식품생물공학과) ;
  • 박영서 (가천대학교 식품생물공학과)
  • Received : 2020.02.17
  • Accepted : 2020.03.20
  • Published : 2020.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

The purpose of this study was to isolate novel lactic acid bacteria to ferment mulberry leaf extract (MLE) and to investigate its anti-diabetic effect. Lactobacillus plantarum SG-053 isolated from gatkimchi was selected to ferment MLE because it exhibited high α-glucosidase inhibitory activity (96.8%) and enhanced the content of 1-deoxynojirimycin (DNJ), an anti-diabetic substance, in fermented MLE up-to 2.2 times. MLE fermented with L. plantarum SG-053 (FMLE) showed growth promoting activity against L6 myotubes and increased the gene expressions of IRS-1, PI3K p85α, and GLUT-4 up-to 1.4, 2.2, and 1.4 times, respectively, and 2-deoxyglucose uptake up-to 40.7%. In rat skeletal muscle tissue, the expressions of PI3K p85α and GLUT-4 increased by 6.4 and 2.1 times, respectively. These results suggest that L. plantarum SG-053 could enhance the DNJ content of MLE by fermentation and that FMLE is effective in ameliorating insulin resistance via activation of the insulin signaling pathway.

본 연구에서는 발효식품으로부터 항당뇨 효능을 지닌 유산균을 분리하여 뽕잎 추출물을 발효하고, 제조된 유산균 발효 뽕잎 추출물의 항당뇨 효능을 평가하였다. 갓김치에서 분리된 Lactobacillus plantarum SG-053은 α-glucosidase 저해 활성이 96.8%로 가장 우수하고, 뽕잎을 발효하여 뽕잎에 존재하는 항당뇨 지표물질인 1-deoxynojirimycin (DNJ)의 함량을 2.2배 증가시키며 우수한 생육 활성을 나타내어 본 연구에서 뽕잎 추출액의 발효에 사용하였다. L. plantarum SG-053으로 발효한 뽕잎 추출물은 L6 근관세포에 대한 세포독성은 없었고, IRS-1, PI3K p85α, GLUT-4 유전자 발현을 각각 1.4, 2.2, 1.4배로 증가시켰으며, 세포의 2-deoxyglucose 흡수를 1 μM의 인슐린보다 높은 수준인 40.7% 증가시켜 인슐린 신호전달 경로를 활성화시킴으로써 세포의 인슐린 저항성을 개선하는 것으로 확인되었다. 경구 당 부하 검사를 통해 유산균 발효 뽕잎 추출물이 포도당 섭취에 의해 증가한 혈당을 빠르게 감소시키고, α-glucosidase의 저해를 통해 maltose의 분해에 의한 혈당 증가를 억제하였다. 유산균 발효 뽕잎 추출물은 SD rat의 허벅지 골격근 조직의 PI3K p85α와 GLUT-4 유전자 발현을 각각 6.4, 2.1배 증가시켜 L6 근관세포에서와 유사한 결과를 나타냈으며, in vivo 근육 조직에서도 인슐린 신호전달경로의 활성화에 영향을 준다는 것을 확인하였다. 본 연구 결과로 L. plantarum SG-053이 뽕잎을 효과적으로 발효하여 DNJ의 함량을 증진시킨다는 것을 확인하였으며, L. plantarum SG-053으로 발효한 뽕잎 추출물은 우수한 항당뇨 효능을 지니는 것을 세포 및 동물실험 수준에서 확인하였다.

Keywords

References

  1. Asano N, Oseki K, Tomioka E, Kizu H, Matsui K. N-Containing sugars from Morus alba and their glycosidase inhibitory activities. Carbohyd. Res. 259: 243-255 (1994) https://doi.org/10.1016/0008-6215(94)84060-1
  2. Bae UJ, Jung ES, Jung SJ, Chae SW, Park BH. Mulberry leaf extract displays antidiabetic activity in db/db mice via Akt and AMPactivated protein kinase phosphorylation. Food Nutr. Res. 62: 1473 (2018)
  3. Bartoli E, Fra GP, Carnevale Schianca GP. The oral glucose tolerance test (OGTT) revisited. Eur. J. Intern. Med. 22: 8-12 (2011) https://doi.org/10.1016/j.ejim.2010.07.008
  4. Bruning JC, Michael MD, Winnay JN, Hayashi T, Horsch D, Accili D, Goodyear LJ, Kahn CR. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol. Cell. 2: 559-569 (1998) https://doi.org/10.1016/S1097-2765(00)80155-0
  5. Cai S, Sun W, Fan Y, Guo X, Xu G, Xu T, Hou Y, Zhao B, Feng X, Liu T. Effect of mulberry leaf (Folium Mori) on insulin resistance via IRS-1/PI3K/Glut-4 signalling pathway in type 2 diabetes mellitus rats. Pharm. Biol. 54: 2685-2691 (2016) https://doi.org/10.1080/13880209.2016.1178779
  6. Caplice E, Fitzgerald GF. Food fermentations: Role of microorganisms in food production and preservation. Int. J. Food. Microbiol. 50: 131-149 (1999) https://doi.org/10.1016/S0168-1605(99)00082-3
  7. Carnevali O, Vivo L, Sulpizio R, Gioacchini G, Olivotto I, Silvi S, Cresci A. Growth improvement by probiotic in European sea bass juveniles (Dicentrarchus labrax, L.), with particular attention to IGF-1, myostatin and cortisol gene expression. Aquaculture 258: 430-438 (2006) https://doi.org/10.1016/j.aquaculture.2006.04.025
  8. Ceriello A. Postprandial hyperglycemia and diabetes complications: is it time to treat? Diabetes 54: 1-7 (2005) https://doi.org/10.2337/diabetes.54.1.1
  9. Choi SW, Lee YJ, Ha SB, Jeon YH, Lee DH. Evaluation of biological activity and analysis of functional constituents from different parts of mulberry (Morus alba L.) tree. J. Korean Soc. Food Sci. Nutr. 44: 823-831 (2015) https://doi.org/10.3746/jkfn.2015.44.6.823
  10. Cubas-Cano E, Gonzales-Fernandez C, Tomas-Pejo E. Evolutionary engineering of Lactobacillus pentosus improves lactic acid productivity from xylose-rich media at low pH. Bioresource Technol. 288: 121540 (2019) https://doi.org/10.1016/j.biortech.2019.121540
  11. Czech MP, Corvera S. Signaling mechanisms that regulate glucose transport. Biol. Chem. 274: 1865-1868 (1999) https://doi.org/10.1074/jbc.274.4.1865
  12. Gao K, Zheng C, Wang T, Zhao H, Wang J, Wang Z, Zhai X, Jia Z, Chen J, Zhoi Y, Wang W. 1-Deoxynojirimycin: occurrence, extraction, chemistry, oral pharmacokinetics, biological activities and in silico target fishing. Molecules 21: E1600 (2016) https://doi.org/10.3390/molecules21111600
  13. Gual P, Le Marchand-Brustel Y, Tanti JF. Positive and negative regulation of insulin signaling through IRS-1 phosphorylation. Biochimie. 87: 99-109 (2005) https://doi.org/10.1016/j.biochi.2004.10.019
  14. Harano Y, Sakamoto A, Izumi K, Shimizu Y, Hoshi M, Shichiri M, Shigeta Y, Ohgaku S, Abe H. Usefulness of maltose for testing glucose tolerance. Am. J. Clin. Nutr. 30: 924-931 (1977) https://doi.org/10.1093/ajcn/30.6.924
  15. Hitendra J, Narotham Prasad BD, Gurumurthy H, Suvarna VC. Role of lactic acid bacteria (LAB) in food preservation. Int. J. Curr. Microbiol. Appl. Sci. 5: 255-257 (2016) https://doi.org/10.20546/ijcmas.2016.508.026
  16. Holzapfel WH, Schillinger U. Introduction to pre- and probiotics. Food Res. Int. 35: 109-116 (2002) https://doi.org/10.1016/S0963-9969(01)00171-5
  17. Honda K, Moto M, Uchida N, He F, Hashizume N. Anti-diabetic effects of lactic acid bacteria in normal and type 2 diabetic mice. J. Clin. Biochem. Nutr. 51: 96-101 (2012) https://doi.org/10.3164/jcbn.11-07
  18. Huang CH, Chen MF, Chung HH, Cheng JT. Antihyperglycemic effect of syringaldehyde in streptozotocin-induced diabetic rats. J. Nat. Prod. 75: 1465-1468 (2012) https://doi.org/10.1021/np3003723
  19. Huang X, Liu G, Gou J, Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. Int. J. Biol. Sci. 14: 1483-1496 (2018) https://doi.org/10.7150/ijbs.27173
  20. Huang DW, Shen SC, Wu JSB. Effects of caffeic acid and cinnamic acid on glucose uptake in insulin-resistant mouse hepatocytes. J. Agr. Food Chem. 57: 7687-7692 (2009) https://doi.org/10.1021/jf901376x
  21. Jeon HJ, Kim SH, Lee BY. Oral glucose and maltose tolerance test and inhibition effect of a-glucosidase of Ecklonia cava extract (seapolynol) and dieckol. J. Korean Soc. Food Sci. Nutr. 47: 347-351 (2018) https://doi.org/10.3746/jkfn.2018.47.3.347
  22. Jeong JH, Lee NK, Cho SH, Jeong DY, Jeong YS. Enhancement of 1-deoxynojirimycin content and a-glucosidase inhibitory activity in mulberry leaf using various fermenting microorganisms isolated from Korean traditional fermented food. Biotechnol. Bioproc. E. 19: 1114-1118 (2014) https://doi.org/10.1007/s12257-014-0277-0
  23. Jung SH, Han JH, Park HS, Lee DH, Kim SJ, Cho HS, Kang JS, Myung CS. Effects of unaltered and bioconverted mulberry leaf extracts on cellular glucose uptake and antidiabetic action in animals. BMC Complem. Altern. M. 19: 55 (2019) https://doi.org/10.1186/s12906-019-2460-5
  24. Kan J, Velliquette RA, Grann K, Burns CR, Scholten J, Tian F, Zhang Q, Gui M. A novel botanical formula prevents diabetes by improving insulin resistance. BMC Complem. Altern. M. 17: 352 (2017) https://doi.org/10.1186/s12906-017-1848-3
  25. Kang DH, Khil LY, Park KS, Lee BH, Moon CK. Effects of cadmium on glucose transport in L6 myocytes. J. Environ. Toxicol. 20: 75-85 (2005)
  26. Kim GN, Kwon YI, Jang HD. Mulberry leaf extract reduces postprandial hyperglycemia with few side effects by inhibiting a-glucosidase in normal rats. J. Med. Food. 14: 712-717 (2011) https://doi.org/10.1089/jmf.2010.1368
  27. Kojima Y, Kimura T, Nakagawa K, Asai A, Hasumi K, Oikawa S, Miyazawa T. Effects of mulberry leaf extract rich in 1-deoxynojirimycin on blood lipid profiles in humans. J. Clin. Biochem. Nutr. 47: 155-161 (2010) https://doi.org/10.3164/jcbn.10-53
  28. Lee WJ, Choi SW. Quantitative changes of polyphenolic compounds in mulberry (Morus alba L.) leaves in relation to varieties, harvest period, and heat processing. Prev. Nutr. Food. Sci. 17: 280-285 (2012) https://doi.org/10.3746/pnf.2012.17.4.280
  29. Lee WC, Kim AJ, Kim SY. The study on the functional materials and effects of mulberry leaf. Food Sci. Ind. 36: 2-14 (2003)
  30. Lee HJ, Lee H, Choi YI, Lee JJ. Effect of lactic acid bacteria-fermented mulberry leaf extract on the improvement of intestinal function in rats. Korean J. Food Sci. An. 37: 561-570 (2017) https://doi.org/10.5851/kosfa.2017.37.4.561
  31. Lee S, Lynn EG, Kim JA, Quon MJ. Protein kinase C-ae phosphorylates insulin receptor substrate-1, -3 and -4 but not -2: isoform specific determinants of specificity in insulin signaling. Endocrinology 149: 2451-2458 (2008) https://doi.org/10.1210/en.2007-1595
  32. Lee S, Park YS. Oligosaccharide production by Leuconostoc lactis CCK940 which has glucansucrase activity. Food Eng. Prog. 21: 383-390 (2017) https://doi.org/10.13050/foodengprog.2017.21.4.383
  33. Lee D, Yu JS, Lee SR, Hwang GS, Kang KS, Park JG, Kim HY, Kim KH, Yamabe N. Beneficial effects of bioactive compounds in mulberry fruits against cisplatin-induced nephrotoxicity. Int. J. Mol. Sci. 19: E1117 (2018) https://doi.org/10.3390/ijms19041117
  34. Li YG, Ji DF, Zhong S, Lin TB, Lv ZQ, Hu GY, Wang X. 1-Deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism in streptozotocin-induced diabetic mice. Sci. Rep. 3: 1377 (2013) https://doi.org/10.1038/srep01377
  35. Li X, Wang N, Yin B, Fang D, Zhao Z, Zhang H, Wang G, Chen W. Lactobacillus plantarum X1 with ${\alpha}$-glucosidase inhibitory activity ameliorates type 2 diabetes in mice. RSC Adv. 6: 63536-63547 (2016) https://doi.org/10.1039/C6RA10858J
  36. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the $2^{-{\Delta}{\Delta}CT}$ method. Methods 25: 402-408 (2001) https://doi.org/10.1006/meth.2001.1262
  37. Mussig K, Staiger H, Fiedler H, Moeschel K, Beck A, Kellerer M, Haring HU. Shp2 is required for protein kinase C-dependent phosphorylation of serine 307 in insulin receptor substrate-1. J. Biol. Chem. 280: 32693-32699 (2005) https://doi.org/10.1074/jbc.M506549200
  38. Park JM, Bong HY, Jeong HI, Kim YK, Kim JY, Kwon O. Postprandial hypoglycemic effect of mulberry leaf in Goto-Kakizaki rats and counterpart Wistar rats. Nutr. Res. Pract. 3: 272-278 (2009) https://doi.org/10.4162/nrp.2009.3.4.272
  39. Ramchandran L, Shah NP. Effect of exopolysaccharides and inulin on the proteolytic, angiotensin-I-converting enzyme- and ${\alpha}$-glucosidase-inhibitory activities as well as on textural and rheological properties of low-fat yogurt during refrigerated storage. J. Dairy Sci. 92: 895-906 (2009) https://doi.org/10.3168/jds.2008-1796
  40. Ryu IH, Kwon TO. Enhancement of piperidine alkaloid contents by lactic acid fermentation of mulberry leaves (Morus alba L.). Korean J. Med. Crop Sci. 20: 472-478 (2012) https://doi.org/10.7783/KJMCS.2012.20.6.472
  41. Saito K, Lee S, Shiuchi T, Toda C, Kamijo M, Inagaki-Ohara K, Okamoto S, Minokoshi Y. An enzymatic photometric assay for 2-deoxyglucose uptake in insulin-responsive tissues and 3T3-L1 adipocytes. Anal. Biochem. 412: 9-17 (2011) https://doi.org/10.1016/j.ab.2011.01.022
  42. Takasu S, Parida IS, Onose S, Ito J, Ikeda R, Yamagishi K, Higuchi O, Tanaka F, Kimura T, Miyazawa T, Nakagawa K. Evaluation of the anti-hyperglycemic effect and safety of microorganism 1-deoxynojiriycin. PLoS One 13: e0199057 (2018) https://doi.org/10.1371/journal.pone.0199057
  43. Zhong Y, Wu S, Chen F, He M, Lin J. Isolation of high ${\gamma}$-aminobutyric acid-producing lactic acid bacteria and fermentation in mulberry leaf powders. Exp. Ther. Med. 18: 147-153 (2019)