Glycoprotein Isolated from Morus indica Linne Enhances Detoxicant Enzyme Activities and Lowers Plasma Cholesterol in ICR Mice

뽕잎 당단백질의 혈중지질 저하 효과 및 항산화 효과

  • Shim, Jae-Uoong (Molecular Biochemistry Laboratory, Biotechnology Research Institute and Center for the Control of Animal Hazards Using Biotechnology, Chonnam National University) ;
  • Lim, Kye-Taek (Molecular Biochemistry Laboratory, Biotechnology Research Institute)
  • 심재웅 (전남대학교 생물공학연구소 분자생화학 교실 및 동물유해인자 제어를 위한 전문인력 양성 사업팀) ;
  • 임계택 (전남대학교 생물공학연구소 분자생화학 교실)
  • Published : 2008.12.31

Abstract

The objective of this study was to evaluate the effects of glycoprotein isolated from Morus indica L. (MIL) on plasma cholesterol levels and on the activities of hepatic detoxicant enzymes in ICR mice. MIL glycoprotein evidenced good scavenging activities against lipid peroxyl radicals. When the mice were treated with Triton WR-1339, the levels of total cholesterol (TC) and low-density lipoprotein (LDL)-cholesterol in plasma increased significantly by 53.9 and 47.5 mg/dL, respectively, as compared to the controls. However, when pretreated with MIL glycoprotein $(100{\mu}g/mL)$, ICR mice showed marked reductions to 55.4 and 47.0 mg/dL, as compared to Triton WR-1339 treatment alone. Interestingly, high density lipoprotein cholesterol levels were unchanged. These results indicate that the MIL glycoprotein is capable of scavenging lipidperoxyl radicals, lowering plasma lipid levels, and increasing the activities of detoxicant enzymes in the mouse liver.

본 연구는 콜레스테롤 억제효과가 밝혀진 뽕잎에서 당단백질을 추출하여 과산화지질 라디칼 억제능력 및 생쥐의 혈장 콜레스테롤 수준과 간 해독효소 활성의 개선효과를 평가하였다. In vivo에서 생쥐에게 뽕잎 당단백질을 20 mg/kg의 농도로 섭취시킨 후 콜레스테롤의 수치를 알아보고, 한편, Triton WR-1339를 투여한 생쥐 그룹에서 혈액 및 간 조직을 적출하여 혈장 콜레스테롤의 수준 변화 및 해독효소의 활성을 측정한 결과, 20 mg/kg의 농도로 뽕잎 당단백질을 섭취시킨 생쥐그룹에서 총 콜레스테롤과 LDL 콜레스테롤의 수준이 급격히 감소하였고, HDL의 경우 증가하는 것을 확인할 수 있었다. 또한 Triton WR-1339를 투여한 고지혈증을 유도한 생쥐 그룹에서도 뽕잎 당단백질의 농도에 따른 총 콜레스테롤과 LDL 콜레스테롤의 유의적인 저하를 확인할 수 있었다. 간의 해독효소 중 항산화 기능을 가지고 있는 SOD, CAT 그리고 GPx의 활성은 뽕잎 당단백질의 섭취에 의해 모두 증가하였으나 특히 SOD, CAT의 활성이 크게 나타났고, 그에 비하여 GPx는 그 유의적 차를 느끼기 어려울 정도의 변화 뿐이었다. 일반적으로, 천연물로부터 추출한 당단백질은 항산화 능력을 가지고 있고, 또한 이런 항산화제는 동맥 혈관조직이나 백혈구를 손상시키는 체내에서 발생된 ROS를 제거하고 체내 혈장지단백질 수준에 있어서 반비례적인 상관관계가 있으며, 결과적으로 혈장 콜레스테롤 수준을 억제할 수 있다고 추론할 수 있다(4,25,26). 따라서 이러한 결과에 미루어볼 때, 뽕잎 당단백질 역시 간 내해독효소의 활성을 증가시킴으로써 체내의 ROS 수준을 감소시키고, 콜레스테롤의 수준을 낮추었으므로 뽕잎 당단백질의 역할이 다른 천연물 유래의 당단백질과 마찬가지로 지단백질과 반비례적인 상관관계가 있는 항산화제 역할을 수행할 수 있다고 사료된다. 앞으로 HMG-CoA reductase에 의한 콜레스테롤 생성과 그게 관련된 유전자 발현 및 그 기전을 분자생화학적인 수준에서 보충적인 연구가 더 수행되어야 할 것이다.

Keywords

References

  1. Hong SG, Seo WS, Jung HK, Kang SM. Protecting effects by rooibos tea against immobilization stress-induced cellular damage in rat. Korean J. Food Sci. Technol. 30: 1222-1228 (1998)
  2. Choi WH, Oh YS, Kim SR, Ahn JY, HA TY. Antioxidative and protective effects of Ulmus davidiana var. japonica extracts on glutamate-induced cytotoxicity in PC 12 cells. Korean J. Food Sci. Technol. 37: 479-483 (2005)
  3. Halliwell B, Gutteridge JM, Role of free radicals and catalytic metal ions in human disease: An overview. Method Enzymol. 186: 1-85 (1990) https://doi.org/10.1016/0076-6879(90)86093-B
  4. Lee SJ, Ko JH, Lim K, Lim KT. 150 kDa glycoprotein isolated from Solanum nigrum Linne enhances activities of detoxicant enzymes and lowers plasmic cholesterol in mice. Pharmacol. Res. 51: 399-408 (2005) https://doi.org/10.1016/j.phrs.2004.11.004
  5. Ha TY, Cho IJ, Seong KS, Lee SH. Effect of Cassia tora ethanol extract on the lipid levels of serum and liver in rats fed high cholesterol diet. J. Korean Soc. Food Sci. Nutr. 30: 171-1176 (2001)
  6. Keys A. Coronary heart disease in seven countries. Circulation 41(suppl 1): 1-19 (1970) https://doi.org/10.1161/01.CIR.41.1.1
  7. Lee WC, Kim AJ, Kim SY. The study on the functional materials and effects of Mulberry leaf. Food Sci. Ind. 36: 2-14 (2003)
  8. Kim MW, Ahn MS, Lim YH. Antioxidative activities of Mulberry leaves extracts on edible soybean oil. Korean J. Food Culture 18: 1-8 (2003)
  9. Hong JH, Ahn JM, Choi SW, Rhee SJ. The effects of Mulberry fruit on the antioxidative defense systems and oxidative stress in the erythrocytes of streptozotocin-induced diabetic rats. Nutr. Sci. 7: 127-132 (2004)
  10. Yoshikumi Y. Inhibition of intestinal ${\alpha}$-glucosidase activity and postprandial hyperglycemia by moranoline and its N-alkyl derivatives. Agr. Biol. Chem. 52: 121-126 (1994)
  11. Asano N. Oseki K, Tomioka E, Kizu H, Matsui K. N-containing sugar from the Morus alba and their glycosidase inhibitory activities. Carbohyd. Res. 259: 243-255 (1994) https://doi.org/10.1016/0008-6215(94)84060-1
  12. Lim KT, Lee SJ, Ko JH, Oh PS. Hypolipidemic effects of glycoprotein isolated from Ficus carica Linnoeus in mice. Korean J. Food Sci. Technol. 37: 624-630 (2005)
  13. Ko JH, Lee SJ, Lim KT. 36 kDa Glycoprotein isolated from Rhus verniciflua Stokes fruit has a protective activity to glucose/glucose oxidase-induced apoptosis in NIH/3T3 cells. Toxicol. in Vitro 19: 353-363 (2005) https://doi.org/10.1016/j.tiv.2004.10.006
  14. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18: 499-502 (1972)
  15. Tercyak AM. Determination of cholesterol and cholesterol esters. J. Nutr. Biochem. 2: 281-292 (1991) https://doi.org/10.1016/0955-2863(91)90089-N
  16. Burke RW, Diamondstone BI, Velapoldi RA, Menis O. Mechanisms of the Liebermann-Burchard and Zak color reactions for cholesterol. Clin. Chem. 20: 781-794 (1974)
  17. Beauchamp C, Fridovich I. Superoxide dismutase: Improved assays and an assay applicable to acrylamide gels. Anal. Biochem. 44: 276-287 (1971) https://doi.org/10.1016/0003-2697(71)90370-8
  18. Thomson JF, Nance SL, Tollaksen SL. Spectophotometric assay of catalase with perborate as substrate. Proc. Soc. Exp. Biol. Med. 157: 33-35 (1978) https://doi.org/10.3181/00379727-157-39984
  19. Mohandas J, Marshall JJ, Duggin GG, Horvath JS, Tiller DJ. Differential distribution of glutathione and glutathione-related enzymes in rabbit kidney. Possible implications in analgesic nephropathy. Biochem. Pharmacol. 33: 1801-1807 (1984) https://doi.org/10.1016/0006-2952(84)90353-8
  20. Godfarb S. Rapid increase in hepatic HMG-CoA reductase activity and in vivo cholesterol synthesis after Triton WR-1339 injection. J. Lipid Res. 19: 489-494 (1978)
  21. Hirsch RL, Kellner A. The pathogenesis of hyperlipemia induced by means of surface-active agents. II. Failure of exchange of cholesterol between the plasma and the liver in rabbits given Triton WR-1339. J. Exp. Med. 104: 15-24 (1966)
  22. Block G, Langseth L. Antioxidant vitamins and disease prevention. Food Technol. 48(7): 80-91 (1994)
  23. Fukuzawa K, Takaishi Y. Antioxidants. J. Act. Oxy. Free Rad. 1:55-70 (1990)
  24. Forman HJ, Fridovich I. Superoxide dismutase: A comparison of rate constants. Arch. Biochem. Biophys. 158: 396-401 (1973) https://doi.org/10.1016/0003-9861(73)90636-X
  25. Lee SJ, Lim KT. Antioxidative effects of glycoprotein isolated from Solanum nigrum linne on oxygen radicals and its cytotoxic effects on the MCF-7 cell. J. Food Sci. 68: 466-470 (2003) https://doi.org/10.1111/j.1365-2621.2003.tb05695.x
  26. Anderson JW, Diwadkar VA, Bridges SR. Selective effects of different antioxidants on oxidation of lipoproteins from rats. Exp. Biol. Med. 218: 376-381 (1998) https://doi.org/10.3181/00379727-218-44307