Protective Effects of Danggui Buxue Tang on a Human Umbilical Vein Endothelialcell Damage Induced by Advanced Glycation End Products

DOI: 10.4236/pp.2012.32030   PDF   HTML     4,064 Downloads   7,026 Views  


Advanced glycation end products (AGEs) have been regarded as a pivotal inducer in diabetes and kinds of diabetic nephropathy. The present studies explored the effects of Danggui Buxue Tang (DBT) that is a Chinese medicinal de- coction on negative charge to Human Umbilical Vein Endothelial Cell (HUVEC) and the related mechanism. Alcian blue staining was established to evaluate the intensity of negative charge on HUVEC. Proteoglycan expressions of AGP and avidin were determined by SDS-PAGE. We observed that DBT can significantly increase negative charge on HU-VEC and up-regulated AGP and avidin expressions and ameliorate AGEs-induced HUVEC apoptosis. Therefore, all results showed DBT had prevention effects against the progression of AGEs-induced damage, and this decoction might be promising agent against proteinuria in diabetic nephropathy.

Share and Cite:

W. Qin, B. He, Y. Bei, R. Wang, L. Feng, Y. Xu, J. Zhu, Z. Zheng, Q. Zhu and H. Nie, "Protective Effects of Danggui Buxue Tang on a Human Umbilical Vein Endothelialcell Damage Induced by Advanced Glycation End Products," Pharmacology & Pharmacy, Vol. 3 No. 2, 2012, pp. 224-233. doi: 10.4236/pp.2012.32030.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] P. Zimmet, K. G. Alberti and J. Shaw, “Global and Societal Implications of the Diabetes Epidemic,” Nature, Vol. 414, No. 6865, 2001, pp. 782-787. doi:10.1038/414782a
[2] K. Susztak, A. C. Raff, M. Schiffer and E. P. Bottinger, “Glucose-Induced Reactive Oxygen Species Cause Apoptosis of Podocytes and Podocyte Depletion at the Onset of Diabetic Nephropathy,” Diabetes, Vol. 55, No. 1, 2006, pp. 225-233. doi:10.2337/diabetes.55.01.06.db05-0894
[3] L. Y. Adeline, K. C. Sourris, B. E. Harcourt and V. Thallas-Bonke, “Disparate Effects on Renal and Oxidative Parameters Following RAGE Deletion, AGE Accumulation Inhibition, or Dietary AGE Control in Experimental Diabetic Nephropathy,” American Journal of Physiology— Renal Physiology, Vol. 298, 2010, pp. 763-770. doi:10.1152/ajprenal.00591.2009
[4] T. T. X. Dong, K. J. Zhao, Q. T. Gao, Z. N. Ji, T. T. Zhu, J. Li, et al., “Chemical and Biological Assessment of a Chinese Herbal Decoction Containing Radix Astragali and Radix Angelicae Sinensis: Determination of Drug Ratio in Having Optimized Properties,” Journal of Agricultural and Food Chemistry, Vol. 54, No. 7, 2006, pp. 2767-2774. doi:10.1021/jf053163l
[5] H. M. Zhang, S. W. Chen, X. F. Deng, X. G. Yang and X. Huang, “Novel Mutations Found in Mitochondrial Diabetes in Chinese Han Population,” Diabetes Research and Clinical Practice, Vol. 76, No. 3, 2007, pp. 425-435. doi:10.1016/j.diabres.2006.09.032
[6] Q. T. Gao, J. K. H. Cheung, J. Li, G. K. Y. Chu, R. Duan, A. W. H. Cheung, et al., “A Chinese Herbal Decoction, Danggui Buxue Tang, Prepared from Radix Astragali and Radix Angelicae Sinensis Stimulates the Immune Responses,” Planta Medica, Vol. 72, No. 13, 2006, pp. 1227- 1231. doi:10.1055/s-2006-947186
[7] Q. T. Gao, J. K. H. Cheung, J. Li, Z. Y. Jiang, G. K. Y. Chu, R. Duan, et al., “A Chinese Herbal Decoction, Danggui Buxue Tang, Activates Extracellular Signal-Regulated Kinase in Cultured T-Lymphocytes,” FEBS Letters, Vol. 581, No. 26, 2007, pp. 5087-5093. doi:10.1016/j.febslet.2007.09.053
[8] D. S. Raj, D. Choudhury, T. C. Welbourne and M. Levi, “Advanced Glycation End Products: A Nephrologist’s Perspective,” American Journal of Kidney Diseases, Vol. 35, No. 3, 2000, pp. 365-380. doi:10.1016/S0272-6386(00)70189-2
[9] Q. T. Gao, R. C. Y. Choi, A. W. H. Cheung, J. T. T. Zhu, J. Li, G. K. Y. Chu, et al., “Danggui Buxue Tang—A Chinese Herbal Decoction Activates the Phosphorylations of Extracellular Signal-Regulated Kinase and Estrogen Receptor Alpha in Cultured MCF-7 Cells,” FEBS Letters, Vol. 581, No. 2, 2007, pp. 233-240. doi:10.1016/j.febslet.2006.12.018
[10] K. C. Sourris and J. M. Forbes, “Interactions between Advanced Glycation End-Products (AGE) and Their Re- ceptors in the Devel-opment and Progression of Diabetic Nephropathy Are These Receptors Valid Therapeutic Targets,” Current Drug Targets, Vol. 10, No. 1, 2009, pp. 42-50. doi:10.2174/138945009787122905
[11] J. M. Bohlender, S. Franke, G. Stein and G. Wolf, “Advanced Glycation End Products and the Kidney,” American Journal of Physiology-Renal Physiology, Vol. 289, No. 4, 2005, pp. 645-659. doi:10.1152/ajprenal.00398.2004
[12] J. L. Olson, “Role of Heparin as a Protective Agent Following Reduction of Renal Mass,” Kidney International, Vol. 25, No. 2, 1984, pp. 376-382. doi:10.1038/ki.1984.27
[13] M. L. Purkerson, D. M. Tollefsen and S. Klahr, “N-Desul- fated/Acetylated Heparin Ameliorates the Progression of Renal Disease in Rats with Subtotal Renal Ablation,” Journal of Clinical Investigation, Vol. 81, No. 1, 1988, pp. 69-74. doi:10.1172/JCI113312
[14] A. M. R. dos Santos, A. V. de Olveirab, C. C. da Sil- vaLemos, C. A. Mandarim-de-Lacerdac and R. Bregmana, “Low Molecular Weight Heparin in the Treatment of Puromycin-Induced Nephrosis,” Pathology Research and Practice, Vol. 202, No. 3, 2006, pp. 157-163. doi:10.1016/j.prp.2005.11.010
[15] L. B. Jaques. “Hepa-rin: An Old Drug with a New Paradigm,” Science, Vol. 206, No. 4418, 1979, pp. 528-533. doi:10.1126/science.386509
[16] L. W. Qi, X. D. Wen, J. Cao, et al., “Rapid and Sensitive Screening and Characterization of Phenolic Acids, Phtha- lides, Saponins and Isoflavonoids in Danggui Buxue Tang by Rapid Resolution Liquid Chromatography/Diode-Array Detection Coupled with Time-of-Flight Mass Spectrometry,” Rapid Communications in Mass Spectrometry, Vol. 22, No. 16, 2008, pp. 2493-2509. doi:10.1002/rcm.3638
[17] Y. H. Xu, S. S. Wang, L. Feng, Q. Zhu, P. Xiang and B. He, “Blockade of PKC-Beta Protects HUVEC from Advanced Glycation End Products Induced Inflammation,” International Immunopharmacology, Vol. 10, No. 12, 2010, pp. 1552-1559. doi:10.1016/j.intimp.2010.09.006
[18] T. Chawla, D. Sharma and A. Singh. “Role of the Renin Angiotensin System in Diabetic Nephropathy,” World Journal of Diabetes, Vol. 1, No. 5, 2010, pp. 141-145. doi:10.4239/wjd.v1.i5.141
[19] R. Nagai, K. Matsumoto, X. Ling, H. Suzuki, T. Araki, and S. Horiuchi, “Glycolal-dehyde, a Reactive Intermediate for Advanced Glycation End Products, Plays an Important Role in the Generation of an Active Ligand for the Macrophage Scavenger Receptor,” Diabetes, Vol. 49, No. 10, 2000, pp. 1714-1723. doi:10.2337/diabetes.49.10.1714
[20] G. Orasanu and J. Plutzky, “The Continuum of Diabetic Vascular Disease: From Macro- to Micro-,” Journal of the American College of Cardiology, Vol. 53, No. 5, 2009, pp. 35-42. doi:10.1016/j.jacc.2008.09.055
[21] B. Haraldsson, J. Nystroem and W. M. Deen, “Properties of the Glomerular Barrier and Mechanisms of Proteinuria,” Physiological Reviews, Vol. 88, No. 2, 2008, pp. 451-487. doi:10.1152/physrev.00055.2006
[22] M. V. Shestakova, I. R. Jarek-Martynowa, N. S. Ivanishina, S. S. Kuharenko, M. N. Yadrihinskaya, et al., “Role of Endothelial Dysfunction in the Development of Cardiorenal Syndrome in Patients with Type 1 Diabetes Mellitus,” Diabetes Research and Clinical Practice, Vol. 68, 2005, pp. 65-72. doi:10.1016/j.diabres.2005.03.009
[23] J. A. Bertolatus and L. G. Hunsicker, “Glomerular Sieving of Anionic and Neutral Bovine Albumins in Proteinuric Rats,” Kidney International, Vol. 28, 1985, pp. 467-476. doi:10.1038/ki.1985.153
[24] K. V. Lemley, K. Blouch, I. Abdullah, D. B. Boothroyd, P. H. Bennett, B. D. Myers, et al., “Glomerular Permselectivity at the Onset of Nephropathy in Type 2 Diabetes Mellitus,” Journal of the American Society of Nephrology, Vol. 11, No. 11, 2000, pp. 2095-2105.
[25] R. V. Iozzo, I. R. Cohen, S. Grassel and A. D. Murdoch, “The Biology of Perlecan: The Multifaceted Heparan Sulphate Proteoglycan of Basement Membranes and Pericellular Matrices,” Biochemical Journal, Vol. 302, 1994, pp. 625-639.
[26] S. G. Hagen, A. F. Michael and R. J. Butkowski, “Immunochemical and Biochemical Evidence for Distinct Basement Membrane Heparin Sulfate Proteoglycans,” Journal of Biological Chemistry, Vol. 268, No. 10, 1993, pp. 7261-7269.
[27] C. J. Raats, B. J. Vanden, M. A. Bakker, B. Oppers-Walgreen, B. J. Pisa, H. B. Dijkman, et al., “Expression of Agrin, Dystroglycan, Utrophin in Normal Renal Tissue and in Experimental Glomerulopathies,” American Journal of Pathology, Vol. 156, 2000, pp. 1749-1765. doi:10.1016/S0002-9440(10)65046-8
[28] G. A. Bjornson, K. Ebefors, M. A. Saleem, P. W. Mathieson, B. Haraldsson and N. J. Sorensson, “Podocyte Proteoglycan Synthesis Is Involved in the Development of Nephrotic Syndrome,” American Journal of Physiol- ogy—Renal Physiology, Vol. 292, 2006, pp. 722-730. doi:10.1152/ajprenal.00433.2005
[29] J. M. Forbes, M. E. Cooper, M. D. Oldfield and M. C. Thomas, “Role of Advanced Glycation End Products in Diabetic Nephropathy,” Journal of the American Society of Nephrology, Vol. 14, Suppl. 3, 2003, pp. 254-258. doi:10.1097/01.ASN.0000077413.41276.17
[30] L. Feng, Y. H. Xu, S. S. Wang, A. Y. Wai, Z. G. Zheng, R. S. Wang, Q. Zhu, et al., “Preventative Effects of 4,4’- Di-phenylmethanebis(methyl) Carbamate Isolated from Cortex Mori on Human Umbilical Vein Endothelial Cell Dysfunction Induced by Advanced Glycation End Products,” Phytotherapy Research, Vol. 10, No. 3, 2011, pp. 35-69.
[31] P. O. Bonetti, L. O. Lerman and A. Lerman, “Endothelial Dysfunction: A Marker of Atherosclerotic Risk,” Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 23, No. 10, 2003, pp. 168-175. doi:10.1161/01.ATV.0000051384.43104.FC
[32] T. Matsui, S. Yamagishi, M. Takeuchi, S. Ueda, K. Fukami and S. Okuda, “Nifedipine, a Calcium Channel Blocker, Inhibits Advanced Glycation End Product (AGE)-Elicited Mesangial Cell Damage by Suppressing AGE Receptor (RAGE) Expression via Peroxisome Prolifera-tor-Activated Receptor-Gamma Activation,” Biochemical and Biophysical Research Communications, Vol. 385, No. 2, 2009, pp. 269-272. doi:10.1016/j.bbrc.2009.05.061
[33] A. Csiszar and Z. Ungvari, “Endothelial Dysfunction and Vascular Inflammation in Type 2 Diabetes: Interaction of AGE/RAGE and TNF-Alpha Signaling,” American Journal of Physiology—Heart and Circulatory Physiology, Vol. 295, 2008, pp. 475-482. doi:10.1152/ajpheart.00644.2008
[34] J. N. Tsoporis, S. Izhar, H. Leong-Poi, J. F. Desjardins, H. J. Huttunen and T. G. Parker, “Interaction with the Receptor for Advanced Glycation End Products (RAGE): A Novel Receptor-Mediated Mechanism for Myocyte Apoptosis Postinfarction,” Circulation Research, Vol. 106, No. 1, 2010, pp. 93-101. doi:10.1161/CIRCRESAHA.109.195834
[35] T. Ishibashi, M. Kawaguchi, K. Sugimoto, H. Uekita, N. Sakamoto and K. Yokoyam, “Advanced Glycation End Product-Mediated Matrix Metallo-Proteinase-9 and Apoptosis via Renin-Angiotensin System in type 2 Diabetes,” Journal of Atherosclerosis and Thrombosis, Vol. 17, 2010, pp. 578-589. doi:10.5551/jat.3590

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.