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해당근 추출물의 항산화 활성 및 최종당화산물에 의한 혈관내피세포 기능장애 억제활성
Preventive Effects of Rosa rugosa Root Extract on Advanced Glycation End product-Induced Endothelial Dysfunction

남미현    (고려대학교 생명공학부   ); 이현순    (고려대학교 보건과학연구소   ); 홍충의    (고려대학교 생명공학부   ); 구윤창    (고려대학교 생명공학부   ); 서문영    ((주)바이오버드   ); 이광원    (고려대학교 생명공학부  );
  • 초록

    혈당강하 효과가 있다고 알려진 해당근 추출물을 이용하여 AGEs 생성 저해에 따른 초기 동맥경화증에 대한 효과에 대하여 검토하였다. 먼저 해당근 추출물이 AGEs에 의하여 생성이 촉진된 ROS를 제거하는 효과가 있는지를 확인하기 위하여 항산화 활성을 측정하였다. 총 플라보노이드 함량을 측정한 결과 해당근의 메탄올 추출물은 $128.1{\pm}2.0\;{\mu}g$ quercetin equivalents(QE)/mg DM,총 폴리페놀 함량은 $345.2{\pm}5.7\;{\mu}g$ gallic acid equivalents(GAE)/mg DM으로 나타났다. 환원력 측정을 위한 FRAP assay는 $2.19{\pm}0.1\;mM$ $FeSO_4{\cdot}7H_2O$ /mg DM으로 $25.5{\pm}0.3$ $FeSO_4{\cdot}7H_2O$ /mg DM 인 ascorbic acid에 비해 약 9% 정도의 환원력을 가지고 있었으며, 전자공여능의 경우 $DPPHSC_{50}$ 값이 $34.2{\pm}0.1\;{\mu}g$ DM/mL로 대조군인 ascorbic acid의 $6.8{\pm}0.1\;{\mu}g$ DM/mL과 비교하여 약 20% 정도의 높은 항산화력을 갖고 있었다. 또한, HPLC 분석을 통해 해당근 생물 100 g을 기준으로 240 mg의 EGCG와 50 mg의 kaempferol을 함유하는 것으로 나타났다. AGEs에 의해 유도된 HUVEC의 ROS 생성 저해 효과는 해당근 추출물 100, $500\;{\mu}g/mL$ 처리 시 각각 63, 77%로 나타났다. 또한, monocyte adherent assay에서 해당근 추출물은 $100\;{\mu}g/mL$ 처리시 정상을 0%로 하였을 때 AGEs에 의해 유도된 단핵구 부착을 33%, $500\;{\mu}g/mL$ 처리시 약 75% 정도로 농도 의존적으로 부착을 저해하는 것을 관찰할 수 있었으며, 유도되지 않은 HUVEC의 저항은 $113{\Omega}{\cdot}cm^2$ 에서 glycer-AGEs 처리 시 $88{\Omega}{\cdot}cm^2$ 로 낮아진 것을 해당근 추출물을 $100\;{\mu}g/mL$ 처리 시 약 $102{\Omega}{\cdot}cm^2$ , $500\;{\mu}g/mL$ 처리시 약 $106{\Omega}{\cdot}cm^2$ 로 저항의 감소를 억제하는 것을 관찰할 수 있었다.

    Rosa rugosa has traditionally been used as a folk remedy for diabetes. The objective of this study was therefore to demonstrate the inhibition of endothelial dysfunction activities through antioxidants and the anti-glycation of Rosa rugosa roots. Dried roots of Rosa rugosa were boiled in methanol for three hours, evaporated and lyophilized with a freeze-dryer. The methanolic extract of Rosa rugosa roots (RRE) was tested for antioxidant activities by measuring total polyphenol (TP) content, flavonoid content, 1,1-diphenyl-2-picrylhydrazyl free radical-scavenging activity (DPPH) assay, and ferric-reducing antioxidant power (FRAP) assay. The total TP content, flavonoid content, FRAP value, and $DPPHSC_{50}$ are $345.2\;{\mu}g$ gallic acid equivalents/mg dry matter (DM), $128.1\;{\mu}g$ quercetin equivalents/mg DM, 2.2 mM $FeSO_4$ /mg DM and $34.2\;{\mu}g$ DM/mL, respectively. Treatment of RRE significantly lowered fluorescent formation due to advanced glycation reaction. In addition, reactive oxygen species (ROS) scavenging assay, monocyte adherent assay and transendothelial electrical resistance (TEER) assay were performed to investigate the possibility that RRE improves endothelial dysfunction-induced diabetic complications. The adhesion of THP-1 to treated HUVEC with RRE ( $100\;{\mu}g/mL$ ; 33% and $500\;{\mu}g/mL$ ; 75%) was significantly reduced compared to HUVEC stimulated by glyceraldehydes-AGEs (advanced glycation end product). The TEER value ( $88\;{\Omega}{\cdot}cm^2$ ) of stimulated HUVEC by glyceraldehydes-AGEs was reduced compared to non-stimulation ( $113\;{\Omega}{\cdot}cm^2$ ). However, normalization with RRE increased endothelial permeability in a dose-dependent manner ( $100\;{\mu}g/mL$ ; $102\;{\Omega}{\cdot}cm^2$ and $500\;{\mu}g/mL$ ; $106\;{\Omega}{\cdot}cm^2$ ). Thus, these results suggest that Rosa rugosa roots could be a novel candidate for the prevention of diabetic complications through antioxidants and inhibition of advanced glycation end product formation.

  • 주제어

    Rosa rugosa root .   antioxidant activities .   endothelial dysfunction .   monocyte adherent assay .   TEER .   advanced glycation end product.  

  • 참고문헌 (33)

    1. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 414: 813-820 (2001) 
    2. Stannard AK, Riddell DR, Bradley NJ, Hassall DG, Graham A, Owen JS. Apolipoprotein E and regulation of cytokine-induced cell adhesion molecule expression in endothelial cells. Atherosclerosis 139: 57-64 (1998) 
    3. Huijberts MS, Schaper NC, Schalkwijk CG. Advanced glycation end products and diabetic foot disease. Diabetes Metab. Res. 1: S19-S24 (2008) 
    4. Altiner D, Kilicgun H. The antioxidant effect of Rosa rugosa. Drug Metab. Drug Interact. 23: 323-327 (2008) 
    5. Wang KJ, Zhang YJ, Yang CR. Antioxidant phenolic compounds from rhizomes of Polygonum paleaceum. J. Ethnopharmacol. 96: 483-487 (2005) 
    6. Amaral S, Oliveira PJ, Ramalho-Santos J. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species. Curr. Diabetes Rev. 4: 46-54 (2008) 
    7. Sato T, Iwaki M, Shimogaito N, Wu X, Yamagishi S, Takeuchi M. TAGE (toxic AGEs) theory in diabetic complications. Curr. Mol. Med. 6: 351-358 (2006) 
    8. Neumann A, Schinzel R, Palm D, Riederer P, Munch G. High molecular weight hyaluronic acid inhibits advanced glycation end product-induced NF-$\kappa$B activation and cytokine expression. FEBS Lett. 453: 283-287 (1999) 
    9. Sima AV, Stancu CS, Simionescu M. Vascular endothelium in atherosclerosis. Cell Tissue Res. 335: 191-203 (2009) 
    10. Jazwa A, Loboda A, Golda S, Cisowski J, Szelag M, Zagorska A, Sroczynska P, Drukala J, Jozkowicz A, Dulak J. Effect of heme and heme oxygenase-1 on vascular endothelial growth factor synthesis and angiogenic potency of human keratinocytes. Free Radical Bio. Med. 40: 1250-1263 (2006) 
    11. Yoo K, Lee C. Evaluation of different methods of antioxidant measurement. Food Sci. Biotechnol. 16: 177-182 (2007)     
    12. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65: 55-63 (1983) 
    13. Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay. Anal. Biochem. 239: 70-76 (1996) 
    14. Ainsworth EA, Gillespie KM. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent. Nat. Protoc. 2: 875-877 (2007) 
    15. Stitt AW, Jenkins AJ, Cooper ME. Advanced glycation end products and diabetic complications. Expert Opin. Inv. Drugs 11: 1205-1223 (2002) 
    16. Miyagawa J, Hanafusa T. Mechanism of atherosclerosis in diabetes: altered cytokine network in the vascular wall. Nippon Rinsho 57: 601-606 (1999) 
    17. Hubbard AK, Rothlein R. Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades. Free Radical Bio. Med. 28: 1379-1386 (2000) 
    18. Takahashi HK, Liu K, Wake H, Mori S, Zhang J, Liu R, Yoshino T, Nishibori M. Prostaglandins E2 inhibits advanced glycation end products-induced adhesion molecule expression, cytokine production and lymphocyte proliferation in human peripheral blood mononuclear cells. J. Pharmacol. Exp. Ther. 331: 656-670 (2009) 
    19. Lee SY, Kim JD, Lee YH, Rhee H, Choi YS. Influence of extract of Rosa rugosa roots on lipid levels in serum and liver of rats. Life Sci. 49: 947-951 (1991) 
    20. Pastore S, Potapovich A, Kostyuk V, Mariani V, Lulli D, De Luca C, Korkina L. Plant polyphenols effectively protect HaCaT cells from ultraviolet C-triggered necrosis and suppress inflammatory chemokine expression. Ann. N.Y. Acad. Sci. 1171: 305-313 (2009) 
    21. Ahmed N. Advanced glycation endproducts - role in pathology of diabetic complications. Diabetes Res. Clin. Pr. 67: 3-21 (2005) 
    22. Bogdanov VY, Osterud B. Cardiovascular complications of diabetes mellitus: The tissue factor perspective. Thromb Res. 125: 112-118 (2010) 
    23. Maksimovic Z, Malencic D, Kovacevic N. Polyphenol contents and antioxidant activity of Maydis stigma extracts. Bioresource Technol. 96: 873-877 (2005) 
    24. Cho EJ, Yokozawa T, Kim HY, Shibahara N, Park JC. Rosa rugosa attenuates diabetic oxidative stress in rats with streptozotocininduced diabetes. Am. J. Chin. Med. 32: 487-496 (2004) 
    25. Jiang MZ, Tsukahara H, Ohshima Y, Todoroki Y, Hiraoka M, Maeda M, Mayumi M. Effects of antioxidants and nitric oxide on TNF-alpha-induced adhesion molecule expression and NF-$\kappa$B activation in human dermal microvascular endothelial cells. Life Sci. 75: 1159-1170 (2004) 
    26. Vlassara H, Bucala R, Striker L. Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab. Invest. 70: 138-151 (1994) 
    27. Han Y, Randell E, Vasdev S, Gill V, Curran M, Newhook LA, Grant M, Hagerty D, Schneider C. Plasma advanced glycation endproduct, methylglyoxal-derived hydroimidazolone is elevated in young, complication-free patients with Type 1 diabetes. Clin. Biochem. 42: 562-569 (2009) 
    28. Ye SQ, Zhang LQ, Adyshev D, Usatyuk PV, Garcia AN, Lavoie TL, Verin AD, Natarajan V, Garcia JGN. Pre-B-cell-colonyenhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation. Microvasc. Res. 70: 142-151 (2005) 
    29. Soedamah-Muthu SS, Chaturvedi N, Schalkwijk CG, Stehouwer CD, Ebeling P, Fuller JH. Soluble vascular cell adhesion molecule-1 and soluble E-selectin are associated with micro- and macrovascular complications in Type 1 diabetic patients. J. Diabetes Complicat. 20: 188-195 (2006) 
    30. Kitahara Y, Takeuchi M, Miura K, Mine T, Matsui T, Yamagishi S. Glyceraldehyde-derived advanced glycation end products (AGEs). A novel biomarker of postprandial hyperglycaemia in diabetic rats. Clin. Exp. Med. 8: 175-177 (2008) 
    31. Nishikawa T, Araki E. Investigation of a novel mechanism of diabetic complications: impacts of mitochondrial reactive oxygen species. Rinsho Byori. 56: 712-719 (2008) 
    32. Nemes-Nagy E, Szocs-Molnar T, Dunca I, Balogh-Samarghitan V, Hobai S, Morar R, Pusta DL, Craciun EC. Effect of a dietary supplement containing blueberry and sea buckthorn concentrate on antioxidant capacity in type 1 diabetic children. Acta Physiol. Hung. 95: 383-393 (2008) 
    33. Jansson S, Engfeldt P. Changed life style can prevent type 2 diabetes. Intervention studies show good results in "pre-diabetics". Lakartidningen 104: 3771-3774 (2007) 
  • 이 논문을 인용한 문헌 (1)

    1. Hwang-Bo, Jeon ; Jang, Kyung Ok ; Chung, Hayoung ; Park, Jong-Hwa ; Lee, Tae Hoon ; Kim, Jiyoung ; Chung, In Sik 2016. "Anti-inflammatory Effect of Lactuca sativa L. Extract in Human Umbilical Vein Endothelial Cells and Improvement of Lipid Levels in Mice Fed a High-fat Diet" 한국식품영양학회지 = The Korean journal of food and nutrition, 29(6): 998~1007     

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