Skip to main content

Advertisement

SpringerLink
Log in

3,4,5,6-Tetrahydroxyxanthone prevents vascular endothelial cell apoptosis induced by high glucose

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Apoptosis of endothelial cells may be an important risk factor contributing to the incidence of vascular complications in diabetes. In the present study, we tested the effect of 3,4,5,6-tetrahydroxyxanthone, a synthetic xanthone derivative, on apoptosis induced in human umbilical vein endothelial cells (HUVEC) by a high glucose concentration. Cell apoptosis was detected using DNA ladder formation and flow cytometric techniques. The expression of Bcl-2 protein was analysed using flow cytometric techniques. Lactate dehydrogenase (LDH) activity and malonyldialdehyde (MDA) content in the medium were measured. Cell viability was assayed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. Exposure of HUVEC to a high glucose concentration (30 mM) for 48 h markedly increased LDH release and MDA content in the medium and induced apoptosis and Bcl-2 protein expression in HUVEC. Pretreatment with 3,4,5,6-tetrahydroxyxanthone (1, 3 or 10 μM) or probucol (10 μM) significantly decreased the level of LDH and MDA in the medium, reduced apoptosis and increased the expression of Bcl-2 protein in HUVEC. These results suggest that 3,4,5,6-tetrahydroxyxanthone inhibits high-glucose-induced endothelial cell apoptosis by increasing Bcl-2 protein expression in HUVEC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7a–f

Similar content being viewed by others

References

  • Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322–1326

    Article  CAS  PubMed  Google Scholar 

  • Basnet P, Kadota S, Shimizu M, Takata Y, Kobayashi M, Namba T (1995) Bellidifolin stimulates glucose uptake in rat 1 fibroblasts and ameliorates hyperglycemia in streptozotocin (STZ)-induced diabetic rats. Planta Med 61:402–405

    CAS  PubMed  Google Scholar 

  • Chai W, Chen J, Wang H, Shen J, Ma L, Ma X (2000) The effects of glucose, insulin and oxidized low density lipoprotein on apoptosis in vascular endothelial cells. Chin Med J (Engl) 113:903–906

    CAS  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 

  • Cohen RA (1993) Pathways controlling healthy and diseased arterial smooth muscle. Am J Cardiol 72:39C–46C

    Article  CAS  PubMed  Google Scholar 

  • Cosentino F, Luscher TF (1997) Endothelial function in coronary artery disease. Cardiologia 42:1221–1227

    CAS  PubMed  Google Scholar 

  • Du XL, Sui GZ, Stockklauser-Farber K, Weiss J, Zink S, Schwippert B, Wu QX, Tschope D, Rosen P (1998) Introduction of apoptosis by high proinsulin and glucose in cultured human umbilical vein endothelial cells is mediated by reactive oxygen species. Diabetologia 41:249–256

    Article  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

    CAS  Google Scholar 

  • Hildeman DA, Mitchell T, Aronow B, Wojciechowski S, Kappler J, Marrack P (2003) Control of Bcl-2 expression by reactive oxygen species. Proc Natl Acad Sci USA 100:15035–15040

    Article  CAS  PubMed  Google Scholar 

  • Jiang DJ, Tan GS, Zhou ZH, Xu KP, Ye F, Li YJ (2002a) 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 (2002b) Probucol preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level. Br J Pharmacol 135:1175–1182

    CAS  PubMed  Google Scholar 

  • Jiang DJ, Hu GY, Jiang JL, Xiang HL, Deng HW, Li YJ (2003a) Relationship between protective effect of xanthone on endothelial cells and endogenous nitric oxide synthase inhibitors. Bioorg Med Chem 11:5171–5177

    Article  CAS  PubMed  Google Scholar 

  • Jiang DJ, Jiang JL, Tan GS, Du YH, Xu KP, Li YJ (2003b) Protective effects of daviditin A against endothelial damage induced by lysophosphatidylcholine. Naunyn Schmiedeberg’s Arch Pharmacol 367:600–606

    CAS  Google Scholar 

  • Kunsch C, Medford RM (1999) Oxidative stress as a regulator of gene expression in the vasculature. Circ Res 85:753–766

    CAS  PubMed  Google Scholar 

  • Lorenzi M, Cagliero E (1991) Pathobiology of endothelial and other vascular cells in diabetes mellitus. Call for data. Diabetes 40:653–659

    CAS  PubMed  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 

  • Marshall HE, Merchant K, Stamler JS (2000) Nitrosation and oxidation in the regulation of gene expression. FASEB J 14:1889–1900

    Article  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

    CAS  Google Scholar 

  • Miura T, Ichiki H, Iwamoto N, Kato M, Kubo M, Sasaki H et al (2001) Antidiabetic activity of the rhizoma of Anemarrhena asphodeloides and active components, mangiferin and its glucoside. Biol Pharm Bull 24:1009–1011

    Article  CAS  PubMed  Google Scholar 

  • Nathan DM (1993) Long-term complications of diabetes mellitus. N Engl J Med 328:1676–1685

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Ortiz A, Ziyadeh FN, Neilson EG (1997) Expression of apoptosis-regulatory genes in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys. J Investig Med 45:50–56

    CAS  PubMed  Google Scholar 

  • Recchioni R, Marcheselli F, Moroni F, Pieri C (2002) Apoptosis in human aortic endothelial cells induced by hyperglycemic condition involves mitochondrial depolarization and is prevented by N-acetyl-l-cysteine. Metabolism 51:1384–1388

    Article  CAS  PubMed  Google Scholar 

  • Tesfamariam B (1994) Free radicals in diabetic endothelial cell dysfunction. Free Radic Biol Med 16:383–391

    Article  CAS  PubMed  Google Scholar 

  • Totzke G, Metzner C, Ulrich-Merzenich G, Ko Y, Sachinidis A, Vetter H (2001) Effect of vitamin E and vitamin C on the DNA synthesis of human umbilical arterial endothelial cells. Eur J Nutr 40:121–126

    Article  CAS  PubMed  Google Scholar 

  • Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C (1995) A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods 184:39–51

    Article  CAS  PubMed  Google Scholar 

  • Wu QD, Wang JH, Fennessy F, Redmond HP, Bouchier-Hayes D (1999) Taurine prevents high-glucose-induced human vascular endothelial cell apoptosis. Am J Physiol 277:C1229–C1238

    CAS  PubMed  Google Scholar 

  • Xiong Y, Li YJ, Deng HW (1994) Protection of l-arginine against oxygen free radicals-injured rabbit aortic endothelium. Acta Pharmacol Sin 15:119–123

    CAS  Google Scholar 

Download references

Acknowledgments

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

Author information

Authors and Affiliations

  1. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410078, China

    Zhong Dai, De-Jian Jiang, Han-Wu Deng & Yuan-Jian Li

  2. The Institute of Pharmacy Pharmacology, Nanhua University, Hengyang, 421001, China

    Duan-Fang Liao

Authors
  1. Zhong Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Duan-Fang Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. De-Jian Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Han-Wu Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuan-Jian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuan-Jian Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dai, Z., Liao, DF., Jiang, DJ. et al. 3,4,5,6-Tetrahydroxyxanthone prevents vascular endothelial cell apoptosis induced by high glucose. Naunyn-Schmiedeberg's Arch Pharmacol 370, 314–319 (2004). https://doi.org/10.1007/s00210-004-0973-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-004-0973-y

Keywords

Search

Navigation