Planta Med 2014; 80(04): 269-276
DOI: 10.1055/s-0033-1360369
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Protective Effects of Oxymatrine on Experimental Diabetic Nephropathy

Changrun Guo
1   State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China
,
Fengyu Han
1   State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China
,
Chunfeng Zhang
1   State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China
,
Wei Xiao
2   Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, P. R. China
,
Zhonglin Yang
1   State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China
› Author Affiliations
Further Information

Publication History

received 27 October 2013
revised 07 January 2014

accepted 13 January 2014

Publication Date:
17 February 2014 (online)

Abstract

Diabetic nephropathy, one of the most common and serious vascular complications of both type 1 and type 2 diabetes mellitus, has become a major contributor of end-stage renal failure. The aims of this study were to investigate the effects and possible underlying action mechanism(s) of oxymatrine on renal damage in diabetic rats. Diabetes was induced in male Sprague-Dawley rats by administering a high-fat diet and an intraperitoneal 30 mg/kg streptozotocin injection. The animals were treated orally with saline, metformin hydrochloride, and oxymatrine at 50, 100, and 150 mg/kg/day for 11 weeks. At the end of the treatment, renal tissue, blood, and urine samples were collected for histological and biochemical examination. The results revealed that oxymatrine significantly decreased blood glucose, urinary protein and albumin excretion, serum creatinine, and blood urea nitrogen in diabetic rats, and ameliorated diabetes-induced glomerular and tubular pathological changes. Furthermore, oxymatrine significantly prevented oxidative stress and reduced the contents of renal advanced glycation end products, transforming growth factor-β1, connective tissue growth factor, and inflammatory cytokines in diabetic rats. All these results indicate that oxymatrine has protective effects on experimental diabetic nephropathy by multiple mechanisms.

 
  • References

  • 1 Lopes A. End-stage renal disease due to diabetes in racial/ethnic minorities and disadvantaged populations. Ethn Dis 2009; 19: S1-S47
  • 2 Leese G, Savage M, Chattington P, Vora J. The diabetic patient with hypertension. Postgrad Med J 1996; 72: 263-268
  • 3 Mishra A, Bhatti R, Singh A, Ishar M. Ameliorative effect of the cinnamon oil from Cinnamomum zeylanicum upon early stage diabetic nephropathy. Planta Med 2010; 76: 412-417
  • 4 UKPDS. United Kingdom Prospective Diabetic Study. Lancet 1998; 352: 837-853
  • 5 Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813-820
  • 6 Tahara A, Tsukada J, Tomura Y, Yatsu T, Shibasaki M. Vasopressin increases type IV collagen production through the induction of transforming growth factor-beta secretion in rat mesangial cells. Pharmacol Res 2008; 57: 142-150
  • 7 Hu Y, Ye S, Zhao L, Zheng M, Chen Y. Hydrochloride pioglitazone decreases urinary TGF-beta1 excretion in type 2 diabetics. Eur J Clin Invest 2010; 40: 571-574
  • 8 Wang Y, Zhao W, Xue R, Zhou Z, Liu F, Han Y, Ren G, Peng Z, Cen S, Chen H. Oxymatrine inhibits hepatitis B infection with an advantage of overcoming drug-resistance. Antivir Res 2011; 89: 227-231
  • 9 Hong-Li S, Lei L, Lei S, Dan Z, De-Li D, Guo-Fen Q, Yan L, Wen-Feng C, Bao-Feng Y. Cardioprotective effects and underlying mechanisms of oxymatrine against ischemic myocardial injuries of rats. Phytother Res 2008; 22: 985-989
  • 10 Gan R, Dong G, Yu J, Wang X, Yang S. Oxymatrine, the main alkaloid component of Sophora roots, protects heart against arrhythmias in rats. Planta Med 2011; 77: 226-230
  • 11 Sugimoto H, Shikata K, Hirata K, Akiyama K, Matsuda M, Kushiro M, Shikata Y, Miyatake N, Miyasaka M, Makino H. Increased expression of intercellular adhesion molecule-1 in diabetic rat glomeruli: glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation. Diabetes 1997; 46: 2075-2081
  • 12 Onozato M, Tojo A, Goto A, Fujita T, Wilcox S. Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: effects of ACEI and ARB. Kidney Int 2002; 61: 186-194
  • 13 Navarro JF, Mora-Fernández C. The role of TNF-α in diabetic nephropathy: pathogenic and therapeutic implications. Cytokine Growth Factor Rev 2006; 17: 441-450
  • 14 Qi W, Chen X, Poronnik P, Pollock CA. Transforming growth factor-β/connective tissue growth factor axis in the kidney. Int J Biochem Cell Biol 2008; 40: 9-13
  • 15 Daroux M, Prévost G, Maillard L, Gaxatte C, Agati V, Schmidt A, Boulanger É. Advanced glycation end-products: implications for diabetic and non-diabetic nephropathies. Diabetes Metab J 2010; 36: 1-10
  • 16 Mao Y, Zeng M, Lu L, Wan M, Li C, Chen C, Fu Q, Wang J, She W, Cai X. Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis: a randomized, double blind, placebo-controlled, multicenter clinical study. World J Gastroenterol 2004; 10: 3269-3273
  • 17 Wu D, Wen W, Qi C, Zhao R, Lü J, Zhong C, Chen Y. Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin. Phytomedicine 2012; 19: 712-718
  • 18 Thomson S, McLennan S, Kirwan P, Heffernan S, Hennessy A, Yue D, Twigg S. Renal connective tissue growth factor correlates with glomerular basement membrane thickness and prospective albuminuria in a non-human primate model of diabetes: possible predictive marker for incipient diabetic nephropathy. J Diabetes Complications 2008; 22: 284-294
  • 19 Mensah B, Obineche E, Galadari S, Chandranath E, Shahin A, Ahmed I, Patel S, Adem A. Streptozotocin-induced diabetic nephropathy in rats: the role of inflammatory cytokines. Cytokine 2005; 31: 180-190
  • 20 Hao H, Shao Z, Tang D, Lu Q, Chen X, Yin X, Wu J, Chen H. Preventive effects of rutin on the development of experimental diabetic nephropathy in rats. Life Sci 2012; 91: 959-967
  • 21 Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the care and use of laboratory animals. Washington: The National Academies Press; 2011
  • 22 Wu D, Wen W, Qi C, Zhao R, Lü J, Zhong C, Chen Y. Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin. Phytomedicine 2012; 19: 712-718
  • 23 Tahara A, Matsuyama Y, Shibasaki M. Effects of antidiabetic drugs in high-fat diet and streptozotocin-nicotinamide-induced type 2 diabetic mice. Eur J Pharmacol 2011; 655: 108-116
  • 24 Veerapur V, Prabhakar K, Thippeswamy B, Bansal P, Srinivasan K, Unnikrishnan M. Antidiabetic effect of Ficus racemosa Linn. stem bark in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats: A mechanistic study. Food Chem 2012; 132: 186-193
  • 25 Wang Y, Campbell T, Perry B, Beaurepaire C, Qin L. Hypoglycemic and insulin sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats. Metabolism 2011; 60: 298-305
  • 26 Zhang S, Yang J, Li H, Li Y, Liu Y, Zhang D, Zhang F, Zhou W, Chen X. Skimmin, a coumarin, suppresses the streptozotocin-induced diabetic nephropathy in Wistar rats. Eur J Pharmacol 2012; 692: 78-83
  • 27 Honoré S, Cabrera W, Genta S, Sánchez S. Protective effect of yacon leaves decoction against early nephropathy in experimental diabetic rats. Food Chem Toxicol 2012; 50: 1704-1715