Effects of Arctiin on Streptozotocin-Induced Diabetic Retinopathy in Sprague-Dawley Rats

 

 Buy Article Permissions and Reprints

Abstract

Diabetic retinopathy is one of the most common and severe complications of diabetes mellitus. Arctiin, a bioactive compound isolated from the dry seeds of Arctium lappa L., has been reported to have antidiabetic activity. In this study, we investigated the effect of arctiin on the serum glucose and HBA1c levels, the blood viscosity, and VEGF expression in the retinal tissues of rats with diabetic retinopathy. We first extracted arctiin from Fructus Arctii and then investigated its chemopreventive effect on streptozotocin-induced diabetic retinopathy in male Sprague-Dawley rats. After the induction of diabetes using streptozotocin (30 mg/kg, i. p.), the rats were randomly divided into five groups (n = 20 per group) and treated with intragastric doses of 30, 90, or 270 mg/kg/d wt of arctiin, 100 mg/kg/d wt of calcium dobesilate, or 0.5 % CMC-Na. Twenty nondiabetic sham-treated rats were treated with 0.5 % CMC-Na. The occurrence of diabetic retinopathy did not differ dramatically among the groups. However, at week 16, the glycosylated haemoglobin (HBA1c) level was significantly decreased in all of the arctiin-treated groups when compared with the control group, and the serum glucose level was also decreased in the rats treated with the highest dose of arctiin. In addition, treatment with arctiin ameliorated retinal oedema, detachment of the retina, and VEGF expression in the retina, as detected using histological and immunochemical examinations. Finally, arctiin increased the viability of retinal microvascular endothelial cells in vitro. Together, these findings demonstrate that arctiin decreases the severity of diabetic complications, demonstrating the importance of this compound as an inhibitor of diabetic retinopathy.

• References

• 1 Alghadyan AA. Diabetic retinopathy – An update. Saudi J Ophthalmol 2011; 25: 99-111
  CrossrefPubMedGoogle Scholar
• 2 Zhao F, Wang L, Liu K. In vitro anti-inflammatory effects of arctigenin, a lignan from Arctium lappa L., through inhibition on iNOS pathway. J Ethnopharmacol 2009; 122: 457-462
  CrossrefPubMedGoogle Scholar
• 3 Wu JG, Wu JZ, Sun LN, Han T, Du J, Ye Q, Zhang H, Zhang YG. Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats. Phytomedicine 2009; 16: 1033-1041
  CrossrefPubMedGoogle Scholar
• 4 Hirose M, Yamaguchi T, Lin C, Kimoto N, Futakuchi M, Kono T, Nishibe S, Shirai T. Effects of arctiin on PhIP-induced mammary, colon and pancreatic carcinogenesis in female Sprague-Dawley rats and MeIQx-induced hepatocarcinogenesis in male F344 rats. Cancer Lett 2000; 155: 79-88
  CrossrefPubMedGoogle Scholar
• 5 Ozturk BT, Bozkurt B, Kerimoglu H, Okka M, Kamis U, Gunduz K. Effect of serum cytokines and VEGF levels on diabetic retinopathy and macular thickness. Mol Vis 2009; 15: 1906-1914
  PubMedGoogle Scholar
• 6 Izuta H, Chikaraishi Y, Adachi T, Shimazawa M, Sugiyama T, Ikeda T, Hara H. Extracellular SOD and VEGF are increased in vitreous bodies from proliferative diabetic retinopathy patients. Mol Vis 2009; 15: 2663-2672
  PubMedGoogle Scholar
• 7 Drel VR, Xu WZ, Zhang J, Kador PF, Ali TK, Shin J, Julius U, Slusher B, Remessy AB, Obrosova IG. Poly (ADP-Ribose) polymerase inhibition counteracts cataract formation and early retinal changes in streptozotocin-diabetic rats. Invest Ophthalmol Vis Sci 2012; 53: 1778-1790
  PubMedGoogle Scholar
• 8 Badole SL, Bodhankar SL. Investigation of antihyperglycaemic activity of aqueous and petroleum ether extract of stem bark of Pongamia pinnata on serum glucose level in diabetic mice. J Ethnopharmacol 2009; 123: 115-120
  CrossrefPubMedGoogle Scholar
• 9 Mirshafiey A, Mehrabian F, Razavi A, Shidfar MR, Namaki S. Novel therapeutic approach by culture filtrate of Cryptococcus neoformans var. gattii (CneF) in experimental immune complex glomerulonephritis. Gen Pharmacol 2000; 34: 311-319
  CrossrefPubMedGoogle Scholar
• 10 Silverman MD, Zamora DO, Pan Y, Texeira PV, Planck SR, Rosenbaum JT. Cell adhesion molecule expression in cultured human iris endothelial cells. Invest Ophthalmol Vis Sci 2001; 42: 2861-2866
  PubMedGoogle Scholar
• 11 Silverman MD, Zamora DO, Pan Y, Texeira PV, Baek SH, Planck SR, Rosenbaum JT. Constitutive and inflammatory mediatorregulated fractalkine expression in human ocular tissues and cultured cells. Invest Ophthalmol Vis Sci 2003; 44: 1608-1615
  CrossrefPubMedGoogle Scholar
• 12 Jain A, Sarraf D, Fong D. Preventing diabetic retinopathy through control of systemic factors. Curr Opin Ophthalmol 2003; 14: 389
  CrossrefPubMedGoogle Scholar
• 13 Ola MS, Nawaz M, Siddiquei MM, Amro SA, El-Asrar AM. Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. J Diabetes Complications 2012; DOI: 10.1016/j.jdiacomp.2011.11.004. , published online DOI: 10.1016/j.jdiacomp.2011.11.004.
  PubMedGoogle Scholar
• 14 Amanda IA, Brian S, Charles H, Lalantha L, Diana B. Hyperglycemia and death in cystic fibrosis-related diabetes. Diabetes Care 2011; 34: 1577-1578
  CrossrefPubMedGoogle Scholar
• 15 Warboys CM, Fraser PA. Hyperglycemia attenuates acute permeability response to advanced glycation end products in retinal microvasculature. Microvasc Res 2010; 80: 174-176
  CrossrefPubMedGoogle Scholar
• 16 Angela G, Holger H, Andrea N, Sabine H, Martin H, Klemens R, Reinhard WH. Natural course of untreated microalbuminuria in children and adolescents with type 1 diabetes and the importance of diabetes duration and immigrant status: longitudinal analysis from the prospective nationwide German and Austrian diabetes survey DPV. Eur J Endocrinol 2012; 28: 2019-2024
  PubMedGoogle Scholar
• 17 Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema. Diabetes Care 2003; 26: 2653
  CrossrefPubMedGoogle Scholar
• 18 Xiang X, Ji PC, Jia JX, Ruo BW, Jian MC, Yun L, Wei GX, Xue JS, Run PL. Protective effects of hydrogen saline on diabetic retinopathy in a streptozotocin-induced diabetic rat model. J Ocul Pharmacol Ther 2012; 28: 76-82
  CrossrefPubMedGoogle Scholar
• 19 Curtis TM, Gardiner TA, Stitt AW. Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?. Eye 2009; 23: 1496-1508
  CrossrefPubMedGoogle Scholar
• 20 Krishnamurti U, Steffes MW. Glycohemoglobin: a primary predictor of the development or reversal of complications of diabetes mellitus. Clin Chem 2001; 47: 1157
  PubMedGoogle Scholar
• 21 Tapp RJ, Tikellis G, Wong TY, Harper CA, Zimmet PZ, Shaw JE. Longitudinal association of glucose metabolism with retinopathy. Diabetes Care 2008; 31: 1349
  CrossrefPubMedGoogle Scholar
• 22 Sabanayagam C, Liew G, Tai ES, Lim SC, Subramaniam T, Wong TY. Relationship between glycated aemoglobin and microvascular complications: is there a natural cut-off point for the diagnosis of diabetes?. Diabetologia 2009; 52: 1279-1289
  CrossrefPubMedGoogle Scholar
• 23 Suganthalakshmi B, Anand R, Kim R, Mahalakshmi R, Karthikprakash S, Namperumalsamy P, Sundaresan P. Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy. Mol Vis 2006; 12: 336-341
  PubMedGoogle Scholar
• 24 Kou X, Qi S, Dai W, Luo L, Yin Z. Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264. 7 cells through suppressing JAK-STAT signal pathway. Int Immunopharmacol 2011; 11: 1095-1102
  CrossrefPubMedGoogle Scholar
• 25 Velcheva I, Damianov P, Mantarova S, Antonova N. Hemorheology and heart rate variability in patients with diabetes mellitus type 2. Clin Hemorheol Microcirc 2011; 49: 513-518
  PubMedGoogle Scholar
• 26 Salazar-Vazquez BY, Intaglietta M, Rodríguez-Morán M, Guerrero-Romero F. Blood pressure and hematocrit in diabetes and the role of endothelial responses in the variability of blood viscosity. Diabetes Care 2006; 29: 1523
  CrossrefPubMedGoogle Scholar
• 27 Junguk H, Kelli S, Adam S, Yu H, Manjusha P, David S, Jagadish HV, Feldman EL. Literature-based discovery of diabetes-and ROS-related targets. BMC Med Genomics 2010; 3: 49
  CrossrefPubMedGoogle Scholar