The Indian Journal of Nutrition and Dietetics

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Effect of Cinnamon and its Procyanidin-B2 on Diabetic Retinopathy in Rats


Affiliations
1 SRR Government Arts and Science College karimnagar, Department of Microbiology, Karimnagar, India
2 SRR Government Arts and Science College karimnagar, Department of Biochemistry, Karimnagar, India
3 National Institute of Nutrition (ICMR), Department of Biochemistry, Hyderabad, India
     

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Advanced glycation end products (AGE) are amalgamated in the development of certain pathophysiologies including diabetic retinopathy (DR). Procyanidin-B2 (PCB2), an active principle of cinnamon, has shown to inhibit AGE formation In current study we inspected the protective role of PCB2 to prevent DR in diabetic rats. Diabetes was induced in Wistar-NIN rats by intraperitoneal injection of streptozotocin (35 mg/kg bodyweight) and the control rats received vehicle alone. The retinal morphology was studied by microscopy and immunohistochemistry of diabetic and control rats. The expression of retinal selective genes analysis was done via real-time PCR. Immunoblotting of diabetic and control rat retina was studied. Gene expression and immunohistochemistry and immunofluorescence analysis of diabetic retina from PCB2 and cinnamon fed rat showed declined expression of VEGF and GFAP and increased expression of NGF. Immunoblotting analysis resulted that feeding of PCB2 significantly reserved the formation of carboxy methyl lysine and RAGE in diabetic rats compare with controls. The results indicate that PCB2 was effective in protecting the diabetic retina from development of diabetic retinopathy in rats owing to its antiglycating potential. Thus, active principle of dietary sources, such as PCB2, may be explored for the prevention or delay of DR.

Keywords

Diabetic Nephropathy, Cinnamon, Procyanidin-B2, AGE, CML, RAGE, STZ-Rat.
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  • Guariguata, L., Whiting, D.R., Hambleton, I., Beagley, J., Linnenkamp, U. and Shaw, J.E. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabet. Res. Clin. Pract., 2013, 103, 137-149.

  • Nanditha, A., Ma, R.C., Ramachandran, A., Snehalatha, C., Chan, J.C., Chia, K.S., et al. Diabetes in Asia and the Pacific: Implications for the Global Epidemic. Diab. Care, 39, 472-485.

  • Leasher, J.L., Bourne, R.R., Flaxman, S.R., Jonas, J.B., Keeffe, J., Naidoo, K., et al. Global estimates on the number of people blind or visually impaired by diabetic retinopathy: A meta-analysis from 1990 to 2010. Diab. Care, 39, 1643-1649.

  • Chakravarthy, U., Hayes, R.G., Stitt, A. W., McAuley, E. and Archer, D.B. Constitutive nitric oxide synthase expression in retinal vascular endothelial cells is suppressed by high glucose and advanced glycation end products. Diabet., 1998, 47, 945-952.

  • Chibber, R., Molinatti, P. A., Rosatto, N., Lambourne, B. and Kohner, E.M. Toxic action of advanced glycation end products on cultured retinal capillary pericytes and endothelial cells: Relevance to diabetic retinopathy. Diabetol., 1997, 40, 156-164.

  • Lu, M., Kuroki, M., Amano, S., Tolentino, M., Keough, K., Kim, I., et al. Advanced glycation end products increase retinal vascular endothelial growth factor expression. J. Clin. Invest., 1998, 101, 1219-1224.

  • Treins, C., Giorgetti-Peraldi, S., Murdaca, J. and Van Obberghen, E. Regulation of vascular endothelial growth factor expression by advanced glycation end products. J. Biologi. Chem., 2001, 276, 43836-43841.

  • Yamagishi, S.I., Amano, S., Inagaki, Y., Okamoto, T., Koga, K., Sasaki, N., et al. Advanced glycation end products-induced apoptosis and over expression of vascular endothelial growth factor in bovine retinal pericytes. Biochem. Biophy. Res. Commun., 2002, 290, 973-978.

  • Clements Jr, R. S., Robison Jr, W.G. and Cohen, M.P. Anti-glycated albumin therapy ameliorates early retinal microvascular pathology in db/db mice. J. Diabet. Complicat., 1998, 12, 28-33.

  • Stitt, A.W., Bhaduri, T., McMullen, C.B.T., Gardiner, T.A. and Archer, D.B. Advanced glycation end products induce blood-retinal barrier dysfunction in normoglycemic rats. Mole. Cell Bio. Res. Commun., 2000, 3, 380-388.

  • Moore, T.C.B., Moore, J.E., Kaji, Y., Frizzell, N., Usui, T., Poulaki, V., et al. The role of advanced glycation end products in retinal microvascular leukostasis. Invest. Ophthalmol. Visual Sci., 2003, 44, 4457-4464.

  • Hammes, H.P., Brownlee, M., Edelstein, D., Saleck, M., Martin, S. and Federlin, K. Aminoguanidine inhibits the development of accelerated diabetic retinopathy in the spontaneous hypertensive rat. Diabetol., 1994, 37, 32-35.

  • Hammes, H.P., Martin, S., Federlin, K., Geisen, K. and Brownlee, M. Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. Proceedings of the National Academy of Sciences of the United States of America, 1991, 88, 1155511558.

  • Wautier, J.L. and Guillausseau, P.J. Advanced glycation end products, their receptors and diabetic angiopathy. Diabet. Metabol., 2001, 27, 535-542.

  • Mrudula, T., Suryanarayana, P., Srinivas, P.N. and Reddy, G.B. Effect of curcumin on hyperglycemia-induced vascular endothelial growth factor expression in streptozotocininduced diabetic rat retina. Biochem. Biophys. Res. Commun., 2007, 361, 528-532.

  • Saraswat, M., Reddy, P.Y., Muthenna, P. and Reddy, G.B. Prevention of non-enzymic glycation of proteins by dietary agents: prospects for alleviating diabetic complications. Br. J. Nutr., 2009, 101, 1714-1721.

  • Kumar, P.A., Reddy, P.Y., Srinivas, P.N. and Reddy, G.B. Delay of diabetic cataract in rats by the antiglycating potential of cumin through modulation of alpha-crystallin chaperone activity. J. Nutr. Biochem., 2009, 20, 553-562.

  • Muthenna, P., Raghu, G., Kumar, P.A., Surekha, M.V. and Reddy, G.B. Effect of cinnamon and its procyanidin-B2 enriched fraction on diabetic nephropathy in rats. Chem. Biol. Interact., 2014, 222, 68-76.

  • Godisela, K.K., Reddy, S.S., Kumar, C.U., Saravanan, N., Reddy, P.Y., Jablonski, M.M., et al. Impact of obesity with impaired glucose tolerance on retinal degeneration in a rat model of metabolic syndrome. Mol. Vis., 2018, 23, 263-274.

  • Aiello, L.P., Avery, R.L., Arrigg, P.G., Keyt, B.A., Jampel, H.D., Shah, S.T., et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. New Engl. J. Med., 1994, 331, 1480-1487.

  • Von Bartheld, C.S. Neurotrophins in the developing and regenerating visual system. Histol. Histopathol., 1998, 13, 437-459.

  • Yamagishi, S.I., Takeuchi, M., Inagaki, Y., Nakamura, K. and Imaizumi, T. Role of advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic microangiopathy. Inter J. Clin. Pharmacol. Res., 2003, 23, 129-134.

  • Brownlee, M. Biochemistry and molecular cell biology of diabetic complications. Nature, 2001, 414, 813-820.

  • King, H., Aubert, R.E. and Herman, W.H. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabet. Care, 1998, 21, 1414-1431.

  • Mohan, V., Sandeep, S., Deepa, R., Shah, B. and Varghese, C. Epidemiology of type 2 diabetes: Indian scenario. Ind. J. Med. Res., 2007, 125, 217-230.

  • Vlassara, H. and Palace, M.R. Diabetes and advanced glycation endproducts. J. Int. Med., 2002, 251, 87-101.

  • Stitt, A.W. The role of advanced glycation in the pathogenesis of diabetic retinopathy. Experi. Mole. Pathol., 2003, 75, 95-108.

  • Hammes, H.P., Bartmann, A., Engel, L. and Wülfroth, P. Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine. Diabetol., 1997, 40, 629-634.

  • Kowluru, R.A., Engerman, R.L. and Kern, T.S. Abnormalities of retinal metabolism in diabetes or experimental galactosemia VIII. Prevention by aminoguanidine. Curr. Eye Res., 2000, 21, 814-819.

  • Urata, Y., Yamaguchi, M., Higashiyama, Y., Ihara, Y., Goto, S., Kuwano, M., et al. Reactive oxygen species accelerate production of vascular endothelial growth factor by advanced glycation end products in RAW264.7 mouse macrophages. Free Radical Biol. Med., 2002, 32, 688-701.

  • Joussen, A.M., Murata, T., Tsujikawa, A., Kirchhof, B., Bursell, S.E. and Adamis, A.P. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am. J. Pathol., 2001, 158, 147-152.

  • Murata, T., Ishibashi, T., Khalil, A., Hata, Y., Yoshikawa, H. and Inomata, H. Vascular endothelial growth factor plays a role in hyperpermeability of diabetic retinal vessels. Ophthalmic Res., 1995, 27, 48-52.

  • Murata, T., Nakagawa, K., Khalil, A., Ishibashi, T., Inomata, H. and Sueishi, K. The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas. Laboratory Invest., 1996, 74, 819-825.

  • Ozerdem, U. and Stallcup, W.B. Early contribution of pericytes to angiogenic sprouting and tube formation. Angiogen, 2003, 6, 241-249.

  • Aiello, L.P., Northrup, J.M., Keyt, B.A., Takagi, H. and Iwamoto, M.A. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch. Ophthalmol., 1995, 113, 15381544.

  • Miller, J.W., Adamis, A.P. and Aiello, L.P. Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy. Diabetes/Metabolism Rev., 1997, 13, 37-50.

  • Pierce, I.A., Avery, R.L., Foley, E.D., Aiello, L.P. and Smith, L.E.H. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proceedings of the National Academy of Sciences of the United States of America, 1995, 92, 905-909.

  • Stone, J., Chan-Ling, T., Pe’er, J., Itin, A., Gnessin, H. and Keshet, E. Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity. Invest. Ophthalmol. Visual Sci., 1996, 37, 290-299.

  • Casaccia-Bonnefil, P., Kong, H. and Chao, M.V. Neurotrophins: The biological paradox of survival factors eliciting apoptosis. Cell Death. Differentiat., 1998, 5, 357-364.

  • Dechant, G. and Barde, Y.A. Signalling through the neurotrophin receptor p75 (NTR). Curr. Opini. Neurobiol., 1997, 7, 413-418.

  • Kaplan, D.R. and Miller, F.D. Neurotrophin signal transduction in the nervous system. Curr. Opini. Neurobiol., 2000, 10, 381-391.

  • Barber, A.J., Antonetti, D.A. and Gardner, T.W. Altered expression of retinal occludin and glial fibrillary acidic protein in experimental diabetes. Invest. Ophthalmol. Visual Sci., 2000, 41, 3561-3568.

  • Liedtke, W., Edelmann, W., Bieri, P.L., Chiu, F. C., Cowan, N.J., Kucherlapati, R., et al. GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron, 1996, 17, 607-615.

  • Stone, J., Itin, A., Alon, T., Pe’er, J., Gnessin, H., Chan-Ling, T., et al. Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J. Neurosci., 1995, 15, 4738-4747.

  • Kim, J., Kim, C.S., Sohn, E. and Kim, J.S. Elevated Nε-(carboxymethyl) lysine is associated with apoptosis of retinal pericytes in streptozotocin-induced diabetic rats. Ophthal. Res., 46, 92-97.

  • Wautier, J.L., Zoukourian, C., Chappey, O., Wautier, M.P., Guillausseau, P.J., Cao, R., et al. Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats. J. Clin. Invest., 1996, 97, 238-243.


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  • Effect of Cinnamon and its Procyanidin-B2 on Diabetic Retinopathy in Rats

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Authors

Muthenna Puppala
SRR Government Arts and Science College karimnagar, Department of Microbiology, Karimnagar, India
Kishore Kumar Godisela
SRR Government Arts and Science College karimnagar, Department of Biochemistry, Karimnagar, India
Bhanuprakash Reddy Geereddy
National Institute of Nutrition (ICMR), Department of Biochemistry, Hyderabad, India
Akileshwari Chandrashaker
National Institute of Nutrition (ICMR), Department of Biochemistry, Hyderabad, India
Raghu Gangula
National Institute of Nutrition (ICMR), Department of Biochemistry, Hyderabad, India

Abstract


Advanced glycation end products (AGE) are amalgamated in the development of certain pathophysiologies including diabetic retinopathy (DR). Procyanidin-B2 (PCB2), an active principle of cinnamon, has shown to inhibit AGE formation In current study we inspected the protective role of PCB2 to prevent DR in diabetic rats. Diabetes was induced in Wistar-NIN rats by intraperitoneal injection of streptozotocin (35 mg/kg bodyweight) and the control rats received vehicle alone. The retinal morphology was studied by microscopy and immunohistochemistry of diabetic and control rats. The expression of retinal selective genes analysis was done via real-time PCR. Immunoblotting of diabetic and control rat retina was studied. Gene expression and immunohistochemistry and immunofluorescence analysis of diabetic retina from PCB2 and cinnamon fed rat showed declined expression of VEGF and GFAP and increased expression of NGF. Immunoblotting analysis resulted that feeding of PCB2 significantly reserved the formation of carboxy methyl lysine and RAGE in diabetic rats compare with controls. The results indicate that PCB2 was effective in protecting the diabetic retina from development of diabetic retinopathy in rats owing to its antiglycating potential. Thus, active principle of dietary sources, such as PCB2, may be explored for the prevention or delay of DR.

Keywords


Diabetic Nephropathy, Cinnamon, Procyanidin-B2, AGE, CML, RAGE, STZ-Rat.

References





DOI: https://doi.org/10.21048/ijnd.2019.56.2.23039