DOI QR코드

DOI QR Code

Antioxidative Role of Geraniin in Lipid Peroxidation of Human LDL

사람 LDL의 지질과산화에 의한 geraniin의 항산화 효과

  • Ho, Ryu-Beung (Department of Food Science and Biotechnology, Kyungsung University)
  • Published : 2004.02.01

Abstract

Crowing evidence indicates that oxidized low density lipoprotein (LDL) nay promote atherogenesis. Therefore, inhibition of LDL oxidation may impede this process. The effect of geraniin on the susceptibility of human low density lipoprotein (LDL) to macrophages-induced oxidation was investigated by monitoring a thiobarbiruric acid reactive substrance (TBARS). The antioxidative activity of geraniin was higher than that of $\alpha$-tocopherol on low density lipoprotein (LDL) oxidation by thiobarbituric acid reactive substance (TBARS). Geraniin inhibited the C $u^{2+}$ mediated oxidation of human LDL in a dose dependent manner at concentration of 50 and 100 $\mu\textrm{g}$/mL. Geraniin, almost completely inhibited the macrophages mediated LDL oxidation in electrophoretic mobility and conjugate diene of LDL oxidation. Also, geraniin almost completely inhibited 0$_2$$^{[-10]}$ at concentration of 100 $\mu\textrm{g}$/mL. The physiological relevance of the antioxidative activity was validated at the cellular level where geraniin inhibited endothelial cell mediated LDL oxidation, When compound with several other antioxidants geraniin showed a high activity equal to natural antioxidants, $\alpha$-tocopherol and ascorbic acid, and the synthetic antioxidant, protocol. These results indicate that geraniin might play a protective antioxidant effects on LDL, probably affecting both the structural properties of macrophage and endothelial cell for the LDL oxidation..

본 연구는 동맥 경화의 원인으로 알려진 사람 oxidized low density lipoprotein (LDL)에 대한 geraniin의 산화 억제 효과에 대하여 실험하였다. 사람 LDL을 C $u^{2+}$유도 LDL로 산화 시킬 때 50와 100 $\mu\textrm{g}$/ml 농도의 geraniin를 첨가하여 TBARS을 측정한 결과 LDL에 대한 항산화가 높았으며 용량 의존형으로 나타났다. Geraniin를 20-100 $\mu\textrm{g}$/ml의 농도를 조절하여 전기 영동에 의한 이동상을 조사한 결과 100 $\mu\textrm{g}$/ml geraniin의 농도에서 거의 완전한 억제 효과를 보였다. 사람 LDL에 C $u^{2+}$로 유도하여 LDL를 산화시킬때 conjugated diene를 보면 geraniin를 100 $\mu\textrm{g}$/ml 첨가하였을 때 억제 효과가 높았다. 또한 geraniin은 동맥의 내피세포에 서도 그 농도에 따라 억제효과를 나타내었다. 그리고 phorbol myristate acetate를 처리한 macrophage 유도활성 산소의 소거 효과는 geraniin의 농도가 100 $\mu\textrm{g}$/ml일때 거의 소거하였다. 이상의 결과로 보아 geraniin는 $\alpha$-tocopherol, ascorbir acid 및 합성 항산화제인 probucol과 거의 비슷한 항산화 활성이 있어 동맥 경화의 예방에 효과적이라는 결론을 얻었다.

Keywords

References

  1. Athereoscler. Thromb. v.11 The antioxidant butylated hudroxytoluence protects against atherosclerosis Bjorkhem,I.;A. Henricheson-Freyschuss;O.Breuer;V.Diczfajusy;L.Berflund;P.Henrikson https://doi.org/10.1161/01.ATV.11.1.15
  2. Anal. Biochem. v.149 Determination of malondialdenhyde by ion-pairing high performance liquid chromatograph Bull,A.W.;L.J.Matnett https://doi.org/10.1016/0003-2697(85)90506-8
  3. Anal. Biochem. v.19 Iodometric measurement of liquid hydroperoxides in human plasma Cramer,G.L.;J.E.Miller;R.B.Pendleton;W.E.M.Lands
  4. Ann. Med. v.23 Effect of antioxidants on oxidative modification of LDL Esterbauer,H.;J.H.Gebicki;M. Dieber-Rotheneder;G.Waeg;H.Rable https://doi.org/10.3109/07853899109150520
  5. Free Radic. Res. Commun. v.6 Continuous monitoring of in vitro oxidation of human low density lipoprotein Esterbauer,H.;G.Striegl;H.Puhl;Rotheneder,M. https://doi.org/10.3109/10715768909073429
  6. Lancet v.341 Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Frankel,E.N.;J.Kanner;J.B.German;E.Parks;J.E.Kinsella https://doi.org/10.1016/0140-6736(93)90206-V
  7. Electrophoresis v.14 Detection by Nile red of agarose fel electrophoresed native and modified low density lipoprotein Greenspan,P.;R.L.Gutman https://doi.org/10.1002/elps.1150140111
  8. Proc. Natl. Acad. Sci. USA v.76 Binding site on macrophages that mediated uptake and degradation of actylated low density lipoprotein, producing massive cholesterol deposition Goldstein,J.L.;S.K.Basu;M.S.Brown https://doi.org/10.1073/pnas.76.1.333
  9. J. Clin. Invest. v.34 The distribution and chemical composition of ultracentrifugally separated liporpotein in human serum Havel,R.J.;H.A.Eder;J.H.Bragdon https://doi.org/10.1172/JCI103182
  10. J. Clin. Invest. v.77 Superoxide mediated modification of low density lipoprotein by arterial smooth muscle cells Heinecke,J.W.;H.Rosen;A.Chait https://doi.org/10.1172/JCI112371
  11. Lancet v.342 Dietary antioxidant flavonoids and risk of coronary heart disease: The Zutphen Elderly Studry Hertog,M.;E.Feskens;P.Hollman;M.Katan;D.Kromhout https://doi.org/10.1016/0140-6736(93)92876-U
  12. Proc. Natl. Acad. Sci. USA v.78 Enhanced macrophage degradation of low density lipo-protein previously tncubated with cultured endotherial cell; recognition by receptor for acetylated low density lipoproteins Henricksen,T.;E.M.Mahoney;D.Stecingerg
  13. J. Clin. Invest. v.27 Culture of human endothelial cells derived from human umbilical vein Jaffe.E.A;R.L.Nachman;C.C.Becker;C.R.Minick
  14. Curr. Opin. Lipidol. v.3 Antioxidants and atherosclerosis Jialal,I.;C.Scaccini https://doi.org/10.1097/00041433-199210000-00004
  15. Biochem. Biophys. Acta. v.1086 β-Carotence inhibits the oxidative modification of low-density lipoprotein. Jialal,I.;E.P.Norkus;L.Cristol.S.M.Grundy https://doi.org/10.1016/0005-2760(91)90164-D
  16. The role of oxidative modification and antioxidant in LDL metabolism and atherosclerosis, in Antioxidant in Therapy and Preventive Medicine Jessup,W.;R.T.Dean;C.V.de Whalpt;Emerit,I.(ed.);Parker,L.(ed.);Auclair,C.(ed.)
  17. Biochem. J. v.270 The oxidative modification of low density lipoproteins by macrophages Leake,D.S.;S.M.Rankin
  18. J. Biol. Chem. v.193 Protein measurement with the Folin phenol reagent Lowry,O.H.;N.J.Rosebrough;A.L.Farr;R.J.Randall
  19. Chem. Nat. compds. v.30 no.1 Phenolic components of geranium sanguineum Mavlyanov,S.M.;S.Y.Islambekov;A.K.Karimov;A.I.Ismailor https://doi.org/10.1007/BF00638415
  20. Arterio-sclerosis v.4 Endothelial and smooth muscle cells after low density lipoproteins in vitro by free radical oxidation Morel,D.W.;P.E.DiCorleto;G.M.Chisholm https://doi.org/10.1161/01.ATV.4.4.357
  21. Ann. Rev. Med. v.43 The role of oxidized low-density lipoproteins in the pathogenesis of atherosclerosis Parthasarathy,S.;D.Steingerg;J.L.Witztum https://doi.org/10.1146/annurev.me.43.020192.001251
  22. Lancet v.339 Wine, alcohol, platelets, and the French Paradox for coronary heart disease Rent,D.;M.De Lorgeril https://doi.org/10.1016/0140-6736(92)91277-F
  23. N. Engl. J. Med. v.320 Beyond choesterol Modifications of low density lipoprotein that increases its atherogenicity Steinberg,D.;S.Prthasarathy;T.E.Catew;J.C.Khoo;J.L.Wiztum https://doi.org/10.1056/NEJM198904063201407
  24. Free. Radic. Biol. Med. v.9 Role of oxidatively modified LDL in atherosclerosis Steinbrecher,U.P.;H.Zhang;M.Lougheed
  25. Proc. Natl. Acad. Sci. USA v.85 Antioxidant defenses and lipid peroxidation in human blood plasma. Stocker,R.;V.W.bowry;B.N.Frei https://doi.org/10.1073/pnas.85.24.9748
  26. Manual of pharmacological calculations with computer programs, 2 ed Tallarida,R.J.;R.B.Murray
  27. Free Radic. Biol. Med. v.15 Molecular Pharmacology of vitamin E:Structural aspects of antioxidant activity. Van Acker S.A.B.;L.H.Koymans;A.Bast https://doi.org/10.1016/0891-5849(93)90078-9
  28. J. Clin. Lnvest. v.88 Role of oxidized low-density lipoprotein in atherogenesis Witztum.J.L;D.Steinberg https://doi.org/10.1172/JCI115499
  29. Biochem Med. v.15 A simple fluorometric assay for lipoprotein in blood plasma. Yaki.K https://doi.org/10.1016/0006-2944(76)90049-1
  30. J. clin. Invest. v.77 Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man Yia-Herttuala, S.;W.Palinski;M.E.Posenfeld;S.Parthasarathy;T.E.Carew;S.Butler;J.L.Witztum;D.Steringers https://doi.org/10.1172/JCI112349
  31. Eur. J. Pharmacol. v.214 Inhibits superoxide release from human neutrophilis Yue,T.L.;P.J.Mekenna;R.R.Ruffolo;G.Z.Feuerstein https://doi.org/10.1016/0014-2999(92)90130-V