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Protective effects of daviditin A against endothelial damage induced by lysophosphatidylcholine

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Abstract

Previous investigations have indicated that endogenous inhibitors of nitric oxide synthase (NOS) such as asymmetric dimethylarginine (ADMA) may play an important role in endothelium dysfunction, and some antioxidant drugs improve endothelium function via reduction of ADMA level. The present study examined the antioxidation and endothelial protection of daviditin A, a xanthone compound. Daviditin A significantly inhibited Cu2+-induced low-density lipoprotein (LDL) oxidation (EC50: 38.7 μM) and scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (EC50: 57.5 μM). Vasodilator responses to acetylcholine in rings of the isolated thoracic aorta were impaired in the presence of lysophosphatidylcholine (LPC)(5 mg/l). Daviditin A (10 or 30 μM) significantly attenuated inhibition by LPC of endothelium-dependent relaxation. Incubation of ECV304 cells with LPC (5 mg/l) for 24 h markedly elevated lactate dehydrogenase (LDH) activity and the levels of malondialdehyde (MDA) and ADMA, and decreased the content of nitric oxide (NO) and the activity of dimethylarginine dimethylaminohydrolase (DDAH). Daviditin A (1, 3 or 10 μM) significantly attenuated the increased release of LDH, increased content of MDA, and decreased level of NO induced by LPC. Daviditin A (3 or 10 μM) significantly inhibited the increased concentration of ADMA. Daviditin A (10 μM) significantly attenuated the decreased activity of DDAH. The present results suggest that daviditin A preserves endothelial dysfunction elicited by LPC, and the protective effect of daviditin A on the endothelium is related to reduction of ADMA concentration.

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References

  • Bode-Böger SM, Böger RH, Kienke S, Junker W, Frölich JC (1996) Elevated L-arginine/dimethylarginie ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits. Biochem Biophys Res Commun 219:598–603

    PubMed  Google Scholar 

  • Böger RH, Bode-Böger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, Blaschke TF, Cooke JP (1998) Asymmetric dimethylarginine: a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 98:1842–1847

    PubMed  Google Scholar 

  • Böger RH, Bode-Böger SM, Sydow K, Heistad DD, Lentz SR (2000a) Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia. Arterioscler Thromb Vasc Biol 20:1557–1564

    Google Scholar 

  • Böger RH, Sydow K, Borlak J, Thum T, Lenzen H, Schubert B, Tsikas D, Bode-Böger SM (2000b) LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylme-thionine-dependent methyltransferases. Circ Res 87:99–105

    PubMed  Google Scholar 

  • Chang CH, Lin CC, Hattori M, Namba T (1994) Effects on anti-lipid peroxidation of Cudrania cochinchinensis var. gerontogea. J Ethnopharmacol 44:79–85

    Article  CAS  PubMed  Google Scholar 

  • Chang MY, Lees AM, Lees RS (1993) Low-density lipoprotein modification and arterial wall accumulation in a rabbit model of atherosclerosis. Biochemistry 32:8518–8524

    CAS  PubMed  Google Scholar 

  • Chen BM, Xia LW, Zhao RQ (1997) Determination of NG,NG-dimethylarginine in human plasma by high-performance liquid Chromatography. J Chromatogr B Biomed Appl 692:467–471

    Article  CAS  Google Scholar 

  • Cooke JP (2000) Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 20:2032–2037

    Google Scholar 

  • Cowan CL, Steffen RP (1995) Lysophosphatidylcholine inhibits relaxation of rabbit abdominal aorta mediated by endothelium-derived nitric oxide and endothelium-derived hyperpolarizing factor independent of protein kinase C activation. Arterioscler Thromb Vasc Biol 15:2290–2297

    CAS  PubMed  Google Scholar 

  • Dart AM, Chin-Dusting JP (1999) Lipids and the endothelium. Cardiovasc Res 43:308–322

    CAS  PubMed  Google Scholar 

  • Feng Q, Lu X, Jones DL, Shen J, Arnold JM (2001) Increased inducible nitric oxide synthase expression contributes to myocardial dysfunction and higher mortality after myocardial infarction in mice. Circulation 104:700–704

    CAS  PubMed  Google Scholar 

  • Frostegard J, Nilsson J, Haegerstrand A, Hamsten A, Wigzell H, Gidlund M (1990) Oxidized low density lipoprotein induces differentiation and adhesion of human monocytes and the monocytic cell line U937. Proc Natl Acad Sci USA 87:904–908

    CAS  Google Scholar 

  • Frostegard J, Haegerstrand A, Gidlund M, Nilsson J (1991) Biologically modified LDL increases the adhesive properties of endothelial cells. Atherosclerosis 90:119–126

    CAS  PubMed  Google Scholar 

  • Gonda R, Takeda T, Akiyama T (2000) Studies on the constituents of Anaxagorea luzonensis A. GRAY. Chem Pharm Bull (Tokyo) 48:1219–1222

    Google Scholar 

  • Havel RJ, Eder HA, Bragdon JH (1955) The distribution and chemical composition of ultra-centrifugally separated lipoproteins in human serum. J Clin Invest 34:1345–1353

    CAS  Google Scholar 

  • Hein TW, Kuo L (1998) LDLs impair vasomotor function of the coronary microcirculation: role of superoxide anions. Circ Res 83:404–414

    CAS  PubMed  Google Scholar 

  • Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP (1999) Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 99:3092–3095

    CAS  PubMed  Google Scholar 

  • Jiang DJ, Tan GS, Zhou ZH, Xu KP, Ye F, Li YJ (2002) Protective effects of demethylbellidifolin on myocardial ischemia-reperfusion injury in rats. Planta Med 68:710–713

    Article  CAS  PubMed  Google Scholar 

  • Jiang JL, Li NS, Li YJ, Deng HW (2002) Probucol preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level. Br J Pharmacol 135:1175–1182

    CAS  PubMed  Google Scholar 

  • Kimoto M, Whitley GS, Tsuji H, Ogawa T (1995) Detection of NG,NG-dimethylarginine dimethylaminohydrolase in human tissues using a monoclonal antibody. J Biochem (Tokyo) 117:237–238

    Google Scholar 

  • Koba S, Pakala R, Watanabe T, Katagiri T, Benedict CR (2000) Synergistic interaction between thromboxane A2 and mildly oxidized low density lipoproteins on vascular smooth muscle cell proliferation. Prostaglandins Leukot Essent Fatty Acids 63:329–335

    Article  CAS  PubMed  Google Scholar 

  • Kugiyama K, Kerns SA, Morrisett JD, Roberts R, Henry PD (1990) Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature 344:160–162

    Google Scholar 

  • Kurose I, Wolf R, Grisham MB, Granger DN (1995) Effects of an endogenous inhibitor of nitric oxide synthesis on postcapillary venules. Am J Physiol 268:H2224–H2231

    CAS  PubMed  Google Scholar 

  • Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, Tsuji H, Reaven GM, Cooke JP (2002) Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 106:987–992

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebroough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265

    CAS  Google Scholar 

  • Mahabusarakam W, Proudfoot J, Taylor W, Croft K (2000) Inhibition of lipoprotein oxidation by prenylated xanthones derived from mangostin. Free Radic Res 33:643–659

    CAS  PubMed  Google Scholar 

  • Minami H, Takahashi E, Fukuyama Y, Kodama M, Yoshizawa T, Nakagawa K (1995) Novel xanthones with superoxide scavenging activity from Garcinia subelliptica. Chem Pharm Bull (Tokyo) 43:347–349

    Google Scholar 

  • Murohara T, Kugiyama K, Ohgushi M, Sugiyama S, Ohta Y, Yasue H (1994) LPC in oxidized LDL elicits vasocontraction and inhibits endothelium-dependent relaxation. Am J Physiol 267:H2441–H2449

    CAS  PubMed  Google Scholar 

  • National Institutes of Health (1986) Guide for the care and use of laboratory animals. NIH publication 86-23

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    CAS  PubMed  Google Scholar 

  • Peres V, Nagem TJ, De Oliveira FF (2000) Tetraoxygenated naturally occurring xanthones. Phytochemistry 55:683–710

    Article  CAS  PubMed  Google Scholar 

  • Stuhlinger MC, Tsao PS, Kimoto M, Cooke JP (2000) Homocysteine induced accumulation of asymmetric dimethylarginine: role of DDAH and effect of antioxidants. Circulation 102 [Suppl II]:177

  • Stuhlinger MC, Tsao PS, Her JH, Kimoto M, Balint RF, Cooke JP (2001) Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine. Circulation 104:2569–2575

    PubMed  Google Scholar 

  • Surdacki A, Nowicki M, Sandmann J, Tsikas D, Böger RH, Bode-Böger SM, Kruszelnicka-Böger RH, Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP (1999) Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 99:3092–3095

    CAS  PubMed  Google Scholar 

  • Tan GS, Xu KP, Xu PS, Hu GY, Li YJ (2002) Studies of the chemical constituents of Swertia davida Franch. Yao Xue Xue Bao 37:630–632

    CAS  PubMed  Google Scholar 

  • Usui M, Matsuoka H, Miyazaki H, Ueda S, Okuda S, Imaizumi T (1998) Increased endogenous nitric oxide synthase inhibitor in patient with congestive heart failure. Life Sci 62:2425–2430

    CAS  PubMed  Google Scholar 

  • Vallance P, Leone A, Calver A, Collier J, Moncada S (1992) Accumulation of an endogenous inhibitor of NO synthesis in chronic renal failure. Lancet 339:572–575

    CAS  PubMed  Google Scholar 

  • Xiong Y, Li YJ, Yu XJ, Liu GZ, Li NS (1996) Endogenous inhibitor of nitric oxide synthesis and lipid peroxidation in hyperlipidemic rabbits. Zhongguo Yao Li Xue Bao 17:149–152

    CAS  PubMed  Google Scholar 

  • Yu XJ, Li YJ, Xiong Y (1994) Increase of an endogenous inhibitor of nitric oxide synthesis in serum of high cholesterol fed rabbits. Life Sci 54:753–758

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

This study was supported by a grant from the Provincial Natural Science Foundation of Hunan, China, No. 02jjy2046.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #88, 410078, Changsha , Hunan, China

    De-Jian Jiang, Jun-Lin Jiang, Yan-Hua Du & Yuan-Jian Li

  2. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #88, 410078, Changsha, Hunan , China

    Gui-Shan Tan & Kang-Ping Xu

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  1. De-Jian Jiang
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Correspondence to Yuan-Jian Li.

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Jiang, DJ., Jiang, JL., Tan, GS. et al. Protective effects of daviditin A against endothelial damage induced by lysophosphatidylcholine. Naunyn-Schmiedeberg's Arch Pharmacol 367, 600–606 (2003). https://doi.org/10.1007/s00210-003-0756-x

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