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Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism

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Abstract

Purpose

Beneficial effects of white mulberry against diabetes mellitus have been reported. However, the molecular mechanisms of how white mulberry can attenuate diabetic retinopathy remain poorly understood. Here, the mechanism underlying the protective effect of Morus alba leaves ethanolic extract on oxidative stress, inflammation, apoptosis, and angiogenesis in diabetic retinopathy was investigated.

Methods

Diabetes was induced by injection of streptozotocin. One week after, M. alba (100 mg/kg) was administrated to the rats daily for 16 weeks.

Results

Morus alba extract showed high content of polyphenolics and free radical scavenging activity. Oral M. alba administration significantly attenuated hyperglycemia and weight loss, and decreased sorbitol, fructose, protein kinase C, pro-inflammatory cytokines, and oxidative stress markers in retinas of the diabetic rats. Moreover, M. alba produced marked down-regulation of caspase-3 and Bax, with concomitant up-regulation of Bcl-2 in the diabetic retinas. M. alba also reduced the expression of VEGF in the retina.

Conclusion

These results indicate that M. alba has protective effect on diabetic retinopathy with possible mechanisms of inhibiting hyperglycemia-induced oxidative stress, apoptosis, inflammation, polyol pathway activation, and VEGF expression in the retina.

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References

  1. Aiello LP, Gardner TW, King GL, Blankenship G, Cavallerano JD, Ferris FL 3rd (1998) Diabetic retinopathy. Diabetes Care 21:143–156

    Article  CAS  Google Scholar 

  2. Yau JW, Rogers SL, Kawasaki R et al (2012) Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35:556–564

    Article  Google Scholar 

  3. Aiello PL (2006) The molecular biology of diabetic retinopathy: opportunities for therapeutic intervention. Adv Stud Ophthalmol 3:8–12

    Google Scholar 

  4. Mohamed Q, Gillies MC, Wong TY (2007) Management of diabetic retinopathy: a systematic review. JAMA 298:902–916

    Article  CAS  Google Scholar 

  5. Santos JM, Tewari S, Kowluru RA (2012) A compensatory mechanism protects retinal mitochondria from initial insult in diabetic retinopathy. Free Radic Biol Med 53:1729–1737

    Article  CAS  Google Scholar 

  6. Mitsuhashi J, Morikawa S, Shimizu K, Ezaki T, Yasuda Y, Hori S (2013) Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats. Exp Eye Res 106:64–73

    Article  CAS  Google Scholar 

  7. Chung SS, Chung SK (2005) Aldose reductase in diabetic microvascular complications. Curr Drug Targets 6:475–486

    Article  CAS  Google Scholar 

  8. Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH (2005) Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr Drug Targets 6:511–524

    Article  CAS  Google Scholar 

  9. Curtis TM, Scholfield CN (2004) The role of lipids and protein kinase Cs in the pathogenesis of diabetic retinopathy. Diabetes Metab Res Rev 20:28–43

    Article  CAS  Google Scholar 

  10. Aiello LP, Bursell SE, Clermont A et al (1997) Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes 46:1473–1480

    Article  CAS  Google Scholar 

  11. Vinores SA, Van Niel E, Swerdloff JL, Campochiaro PA (1993) Electron microscopic immunocytochemical demonstration of blood-retinal barrier breakdown in human diabetics and its association with aldose reductase in retinal vascular endothelium and retinal pigment epithelium. Histochem J 25:648–663

    Article  CAS  Google Scholar 

  12. Yan SF, Ramasamy R, Naka Y, Schmidt AM (2003) Glycation, inflammation, and RAGE: a scaffold for the macrovascular complications of diabetes and beyond. Circ Res 93:1159–1169

    Article  CAS  Google Scholar 

  13. Singh CK, Kumar A, Hitchcock DB, Fan D, Goodwin R, LaVoie HA (2011) Resveratrol prevents embryonic oxidative stress and apoptosis associated with diabetic embryopathy and improves glucose and lipid profile of diabetic dam. Mol Nutr Food Res 55:1186–1196

    Article  CAS  Google Scholar 

  14. Behl Y, Krothapalli P, Desta T, DiPiazza A, Roy S, Graves DT (2008) Diabetes-enhanced tumor necrosis factor-alpha production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy. Am J Pathol 172:1411–1418

    Article  Google Scholar 

  15. Dillard CJ, German JB (2000) Phytochemicals: nutraceuticals and human health. J Sci Food Agric 80:1744–1756

    Article  CAS  Google Scholar 

  16. Amarowicz R, Pegg RB, Bautista DA (2000) Antibacterial activity of green tea polyphenols against Escherichia coli K 12. Nahrung 44:60–62

    Article  CAS  Google Scholar 

  17. Ercisli S (2004) A short review of the fruit germplasm resources of Turkey. Genet Resour Crop Evol 51:419–435

    Article  Google Scholar 

  18. Arabshahi-D S, Vishalakshi Devi D, Urooj A (2007) Evaluation of antioxidant activity of some plant extracts and their heat, pH and storage stability. Food Chem 100:1100–1105

    Article  CAS  Google Scholar 

  19. Du J, He ZD, Jiang RW, Ye WC, Xu HX, But PP (2003) Antiviral flavonoids from the root bark of Morus alba L. Phytochemistry 62:1235–1238

    Article  CAS  Google Scholar 

  20. Pan G, Lou C (2008) Isolation of an 1-aminocyclopropane-1-carboxylate oxidase gene from mulberry (Morus alba L.) and analysis of the function of this gene in plant development and stresses response. J Plant Physiol 165:1204–1213

    Article  CAS  Google Scholar 

  21. Sun F, Shen L, Ma Z (2011) Screening for ligands of human aromatase from mulberry (Mori alba L.) leaf by using high-performance liquid chromatography/tandem mass spectrometry. Food Chem 126:1337–1343

    Article  CAS  Google Scholar 

  22. Zhang M, Chen M, Zhang HQ, Sun S, Xia B, Wu FH (2009) In vivo hypoglycemic effects of phenolics from the root bark of Morus alba. Fitoterapia 80:475–477

    Article  CAS  Google Scholar 

  23. Waterman PG, Mole S (1994) Analysis of phenolic plant metabolites. Blackwell Scientific Publication, Oxford

    Google Scholar 

  24. Jia Z, Tang M, Wu Ju (1999) The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem 64:555–559

    Article  Google Scholar 

  25. Brandwilliams W, Cuvelier M, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. Food Sci Technol 28:25–30

    CAS  Google Scholar 

  26. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 26:1231–1237

    Article  CAS  Google Scholar 

  27. El-Seifi SA-MA, Badir N (1993) The effect of Ambrosia maritima and Cleome droserifolia on insulin release in vitro. J Egypy Ger Soc Zool 12:347–363

    Google Scholar 

  28. El-Sayyad HI, El-Sherbiny MA, Sobh MA, Abou-El-Naga AM, Ibrahim MA, Mousa SA (2011) Protective effects of Morus alba leaves extract on ocular functions of pups from diabetic and hypercholesterolemic mother rats. Int J Biol Sci 7:715–728

    Article  CAS  Google Scholar 

  29. Trinder P (1969) Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 6:24–27

    Article  CAS  Google Scholar 

  30. Baker JR, Metcalf PA, Holdaway IM, Johnson RN (1985) Serum fructosamine concentration as measure of blood glucose control in type I (insulin dependent) diabetes mellitus. Br Med J (Clin Res Ed) 290:352–355

    Article  CAS  Google Scholar 

  31. Abraham EC, Huff TA, Cope ND, Wilson JB Jr, Bransome ED Jr, Huisman TH (1978) Determination of the glycosylated hemoglobins (HB AI) with a new microcolumn procedure. Suitability of the technique for assessing the clinical management of diabetes mellitus. Diabetes 27:931–937

    Article  CAS  Google Scholar 

  32. Clements RS Jr, Morrison AD, Winegrad AI (1969) Polyol pathway in aorta: regulation by hormones. Science 166:1007–1008

    Article  CAS  Google Scholar 

  33. Foreman D, Gaylor L, Evans E, Trella C (1973) A modification of the Roe procedure for determination of fructose in tissues with increased specificity. Anal Biochem 56:584–590

    Article  CAS  Google Scholar 

  34. Preuss HG, Jarrell ST, Scheckenbach R, Lieberman S, Anderson RA (1998) Comparative effects of chromium, vanadium and gymnema sylvestre on sugar-induced blood pressure elevations in SHR. J Am Coll Nutr 17:116–123

    Article  CAS  Google Scholar 

  35. Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  Google Scholar 

  36. Cohen G, Dembiec D, Marcus J (1970) Measurement of catalase activity in tissue extracts. Anal Biochem 34:30–38

    Article  CAS  Google Scholar 

  37. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. FEBS Eur J Biochem 47:469–474

    Article  CAS  Google Scholar 

  38. Matkovics B, Szabo L, Varga IS (1998) Determination of enzyme activities in lipid peroxidation and glutathione pathways (in Hungarian). Lab Diagn 15:248–249

    Google Scholar 

  39. PKC-DRS Study Group (2005) The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy: initial results of the Protein Kinase C beta Inhibitor Diabetic Retinopathy Study (PKC-DRS) multicenter randomized clinical trial. Diabetes 54:2188–2197

    Article  Google Scholar 

  40. Palsamy P, Subramanian S (2010) Ameliorative potential of resveratrol on proinflammatory cytokines, hyperglycemia mediated oxidative stress, and pancreatic beta-cell dysfunction in streptozotocin-nicotinamide-induced diabetic rats. J Cell Physiol 224:423–432

    Article  CAS  Google Scholar 

  41. Mohammadi J, Naik PR (2012) The histopathologic effects of Morus alba leaf extract on the pancreas of diabetic rats. Turk J Biol 36:211–216

    Google Scholar 

  42. van Dijk TH, van der Sluijs FH, Wiegman CH, Baller JF, Gustafson LA, Burger HJ (2001) Acute inhibition of hepatic glucose-6-phosphatase does not affect gluconeogenesis but directs gluconeogenic flux toward glycogen in fasted rats. A pharmacological study with the chlorogenic acid derivative S4048. J Biol Chem 276:25727–25735

    Article  Google Scholar 

  43. Hamdy SM (2012) Effect of Morus alba Linn extract on enzymatic activities in diabetic rats. J Appl Sci Res 8:10–16

    CAS  Google Scholar 

  44. Asano N, Yamashita T, Yasuda K, Ikeda K, Kizu H, Kameda Y (2001) Polyhydroxylated alkaloids isolated from mulberry trees (Morus alba L.) and silkworms (Bombyx mori L.). J Agric Food Chem 49:4208–4213

    Article  CAS  Google Scholar 

  45. Laddha GPBS, Mahale V, Baile SB (2012) Antidiabetic effect of Morus alba on rabbit as animal model. Int Res J Pharm 3:334–336

    Google Scholar 

  46. Naowaboot J, Pannangpetch P, Kukongviriyapan V, Kukongviriyapan U, Nakmareong S, Itharat A (2009) Mulberry leaf extract restores arterial pressure in streptozotocin-induced chronic diabetic rats. Nutr Res 29:602–608

    Article  CAS  Google Scholar 

  47. Maritim AC, Sanders RA, Watkins JB 3rd (2003) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17:24–38

    Article  CAS  Google Scholar 

  48. Rains JL, Jain SK (2011) Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med 50:567–575

    Article  CAS  Google Scholar 

  49. Howlett J, Ashwell M (2008) Glycemic response and health: summary of a workshop. Am J Clin Nutr 87:212S–216S

    CAS  Google Scholar 

  50. Lakshminarayanan S, Gardner TW, Tarbell JM (2000) Effect of shear stress on the hydraulic conductivity of cultured bovine retinal microvascular endothelial cell monolayers. Curr Eye Res 21:944–951

    Article  CAS  Google Scholar 

  51. Hammes HP, Lin J, Wagner P, Feng Y, Vom Hagen F, Krzizok T (2004) Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy. Diabetes 53:1104–1110

    Article  CAS  Google Scholar 

  52. Kowluru RA, Chan PS (2007) Oxidative stress and diabetic retinopathy. Exp Diabetes Res 2007:43603

    Google Scholar 

  53. Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M (2003) A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes 52:506–511

    Article  CAS  Google Scholar 

  54. Liu CT, Chen KM, Lee SH, Tsai LJ (2000) Effect of supplemental l-arginine on the function of T lymphocytes and the formation of advanced glycosylated end products in rats with streptozotocin-induced diabetes. Nutrition 21:615–623

    Article  Google Scholar 

  55. Li K, Yang HX (2006) Value of fructosamine measurement in pregnant women with abnormal glucose tolerance. Chin Med J (Engl) 119:1861–1865

    CAS  Google Scholar 

  56. Dikalov S (2011) Cross talk between mitochondria and NADPH oxidases. Free Radic Biol Med 51:1289–1301

    Article  CAS  Google Scholar 

  57. Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070

    Article  CAS  Google Scholar 

  58. Kowluru RA, Kowluru V, Xiong Y, Ho YS (2006) Overexpression of mitochondrial superoxide dismutase in mice protects the retina from diabetes-induced oxidative stress. Free Radic Biol Med 41:1191–1196

    Article  CAS  Google Scholar 

  59. Soufi FG, Mohammad-Nejad D, Ahmadieh H (2012) Resveratrol improves diabetic retinopathy possibly through oxidative stress—nuclear factor kappaB—apoptosis pathway. Pharmacol Rep 64:1505–1514

    Article  CAS  Google Scholar 

  60. Oh H, Ko EK, Jun JY, Oh MH, Park SU, Kang KH (2002) Hepatoprotective and free radical scavenging activities of prenylflavonoids, coumarin, and stilbene from Morus alba. Planta Med 68:932–934

    Article  CAS  Google Scholar 

  61. Iqbal S, Younas U, Sirajuddin Chan KW, Sarfraz RA, Uddin K (2012) Proximate composition and antioxidant potential of leaves from three varieties of Mulberry (Morus sp.): a comparative study. Int J Mol Sci 13:6651–6664

    Article  CAS  Google Scholar 

  62. Das Evcimen N, King GL (2007) The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res 55:498–510

    Article  CAS  Google Scholar 

  63. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M (2000) High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C–dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49:1939–1945

    Article  CAS  Google Scholar 

  64. Williams B, Gallacher B, Patel H, Orme C (1997) Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro. Diabetes 46:1497–1503

    Article  CAS  Google Scholar 

  65. Ganz MB, Seftel A (2000) Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E. Am J Physiol Endocrinol Metab 278:E146–E152

    CAS  Google Scholar 

  66. Ha H, Yu MR, Choi YJ, Kitamura M, Lee HB (2002) Role of high glucose-induced nuclear factor-kappaB activation in monocyte chemoattractant protein-1 expression by mesangial cells. J Am Soc Nephrol 13:894–902

    CAS  Google Scholar 

  67. Frank RN (2002) Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am J Ophthalmol 133:693–698

    Article  CAS  Google Scholar 

  68. Miwa K, Nakamura J, Hamada Y, Naruse K, Nakashima E, Kato K (2003) The role of polyol pathway in glucose-induced apoptosis of cultured retinal pericytes. Diabetes Res Clin Pract 60:1–9

    Article  CAS  Google Scholar 

  69. Safi SZ, Qvist R, Kumar S, Batumalaie K, Ismail IS (2014) Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets. Biomed Res Int 2014:801269

    Article  Google Scholar 

  70. Oates PJ (2002) Polyol pathway and diabetic peripheral neuropathy. Int Rev Neurobiol 50:325–392

    Article  CAS  Google Scholar 

  71. El-Remessy AB, Abou-Mohamed G, Caldwell RW, Caldwell RB (2003) High glucose-induced tyrosine nitration in endothelial cells: role of eNOS uncoupling and aldose reductase activation. Invest Ophthalmol Vis Sci 44:3135–3143

    Article  Google Scholar 

  72. Tang J, Du Y, Petrash JM, Sheibani N, Kern TS (2013) Deletion of aldose reductase from mice inhibits diabetes-induced retinal capillary degeneration and superoxide generation. PLoS ONE 8:e62081

    Article  CAS  Google Scholar 

  73. Rao ARSP, Veeresham C, Asres K (2015) Aldose reductase inhibitory and antiglycation activities of four medicinal plant standardized extracts and their main constituents for the prevention of diabetic complications. Ethiop Pharm J 31:1–14

    Article  Google Scholar 

  74. van Hecke MV, Dekker JM, Nijpels G, Moll AC, Heine RJ, Bouter LM (2005) Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study. Diabetologia 48:1300–1306

    Article  CAS  Google Scholar 

  75. Demircan N, Safran BG, Soylu M, Ozcan AA, Sizmaz S (2006) Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye (Lond) 20:1366–1369

    Article  CAS  Google Scholar 

  76. Vincent JA, Mohr S (2007) Inhibition of caspase-1/interleukin-1beta signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes 56:224–230

    Article  CAS  Google Scholar 

  77. Mohr S, Xi X, Tang J, Kern TS (2002) Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients. Diabetes 51:1172–1179

    Article  CAS  Google Scholar 

  78. Fan F, Stoeltzing O, Liu W, McCarty MF, Jung YD, Reinmuth N (2004) Interleukin-1beta regulates angiopoietin-1 expression in human endothelial cells. Cancer Res 64:3186–3190

    Article  CAS  Google Scholar 

  79. Aveleira CA, Lin CM, Abcouwer SF, Ambrosio AF, Antonetti DA (2010) TNF-alpha signals through PKCzeta/NF-kappaB to alter the tight junction complex and increase retinal endothelial cell permeability. Diabetes 59:2872–2882

    Article  CAS  Google Scholar 

  80. Grant MB, Mames RN, Fitzgerald C, Hazariwala KM, Cooper-DeHoff R, Caballero S (2000) The efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy: a randomized controlled study. Diabetes Care 23:504–509

    Article  CAS  Google Scholar 

  81. Huang H, Gandhi JK, Zhong X, Wei Y, Gong J, Duh EJ (2011) TNF alpha is required for late BRB breakdown in diabetic retinopathy, and its inhibition prevents leukostasis and protects vessels and neurons from apoptosis. Invest Ophthalmol Vis Sci 52:1336–1344

    Article  CAS  Google Scholar 

  82. Choi EM, Hwang JK (2005) Effects of Morus alba leaf extract on the production of nitric oxide, prostaglandin E2 and cytokines in RAW264.7 macrophages. Fitoterapia 76:608–613

    Article  Google Scholar 

  83. Chung KO, Kim BY, Lee MH, Kim YR, Chung HY, Park JH (2003) In-vitro and in-vivo anti-inflammatory effect of oxyresveratrol from Morus alba L. J Pharm Pharmacol 55:1695–1700

    Article  CAS  Google Scholar 

  84. Chen YC, Tien YJ, Chen CH, Beltran FN, Amor EC, Wang RJ (2013) Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signaling. BMC Complement Altern Med 13:45

    Article  Google Scholar 

  85. Kollar P, Barta T, Hosek J, Soucek K, Zavalova VM, Artinian S (2013) Prenylated flavonoids from Morus alba L. cause inhibition of G1/S transition in THP-1 human leukemia cells and prevent the lipopolysaccharide-induced inflammatory response. Evid Based Complement Altern Med 2013:350519

    Article  Google Scholar 

  86. Kumar B, Gupta SK, Nag TC, Srivastava S, Saxena R, Jha KA, Srinivasan BP (2014) Retinal neuroprotective effects of quercetin in streptozotocin-induced diabetic rats. Exp Eye Res 125:193–202

    Article  CAS  Google Scholar 

  87. Ola MS, Ahmed MM, Ahmad R, Abuohashish HM, Al-Rejaie SS, Alhomida AS (2015) Neuroprotective effects of rutin in streptozotocin-induced diabetic rat retina. J Mol Neurosci 56:440–448

    Article  CAS  Google Scholar 

  88. Yang Y, Andresen BT, Yang K, Zhang Y, Li X, Wang H (2010) Association of vascular endothelial growth factor -634C/G polymorphism and diabetic retinopathy in type 2 diabetic Han Chinese. Exp Biol Med (Maywood) 235:1204–1211

    Article  CAS  Google Scholar 

  89. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487

    Article  CAS  Google Scholar 

  90. Hong Y, Kim MY, Yoon M (2011) The anti-angiogenic herbal extracts Ob-X from Morus alba, Melissa officinalis, and Artemisia capillaris suppresses adipogenesis in 3T3-L1 adipocytes. Pharm Biol 49:775–783

    Article  Google Scholar 

  91. Tilton RG, Kawamura T, Chang KC, Ido Y, Bjercke RJ, Stephan CC (1997) Vascular dysfunction induced by elevated glucose levels in rats is mediated by vascular endothelial growth factor. J Clin Invest 99:2192–2202

    Article  CAS  Google Scholar 

  92. Montero JA, Ruiz-Moreno JM, Correa ME (2011) Intravitreal anti-VEGF drugs as adjuvant therapy in diabetic retinopathy surgery. Curr Diabetes Rev 7:176–184

    Article  CAS  Google Scholar 

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  1. Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Salah Salim St., Beni-Suef, 62514, Egypt

    Ayman M. Mahmoud, Sanaa M. Abd El-Twab & Eman S. Abdel-Reheim

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  1. Ayman M. Mahmoud
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Mahmoud, A.M., Abd El-Twab, S.M. & Abdel-Reheim, E.S. Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism. Eur J Nutr 56, 1671–1684 (2017). https://doi.org/10.1007/s00394-016-1214-0

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