The Role of Aldose Reductase in Polyol Pathway: An Emerging Pharmacological Target in Diabetic Complications and Associated Morbidities


Cite item

Full Text

Abstract

The expression of aldose reductase leads to a variety of biological and pathological effects. It is a multifunctional enzyme which has a tendency to reduce aldehydes to the corresponding sugar alcohol. In diabetic conditions, the aldose reductase enzyme converts glucose into sorbitol using nicotinamide adenine dinucleotide phosphate as a cofactor. It is a key enzyme in polyol pathway which is a surrogate course of glucose metabolism. The polyol pathway has a significant impact on the aetiology of complications in individuals with end-stage diabetes. The exorbitant level of sorbitol leads to the accumulation of intracellular reactive oxygen species in diabetic heart, neurons, kidneys, eyes and other vasculatures, leading to many complications and pathogenesis. Recently, the pathophysiological role of aldose reductase has been explored with multifarious perspectives. Research on aldose reductase suggest that besides implying in diabetic complications, the enzyme also turns down the lipid-derived aldehydes as well as their glutathione conjugates. Although aldose reductase has certain lucrative role in detoxification of toxic lipid aldehydes, its overexpression leads to intracellular accumulation of sorbitol which is involved in secondary diabetic complications, such as neuropathy, cataractogenesis, nephropathy, retinopathy and cardiovascular pathogenesis. Osmotic upset and oxidative stress are produced by aldose reductase via the polyol pathway. The inhibition of aldose reductase alters the activation of transcription factors like NF-ƙB. Moreover, in many preclinical studies, aldose reductase inhibitors have been observed to reduce inflammation-related impediments, such as asthma, sepsis and colon cancer, in diabetic subjects. Targeting aldose reductase can bestow a novel cognizance for this primordial enzyme as an ingenious strategy to prevent diabetic complications and associated morbidities. In this review article, the significance of aldose reductase is briefly discussed along with their prospective applications in other afflictions.

About the authors

Jeetendra Gupta

Department of Pharmacology, Institute of Pharmaceutical Research, GLA University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Hers, H.G. Le mécanisme de la transformation de glucose en fructose par les vésicules séminales. Biochim. Biophys. Acta, 1956, 22(1), 202-203. doi: 10.1016/0006-3002(56)90247-5 PMID: 13373872
  2. Ramana, K.V. Aldose reductase: New insights for an old enzyme. Biomol. Concepts, 2011, 2(1-2), 103-114. doi: 10.1515/bmc.2011.002 PMID: 21547010
  3. Van Heyningen, R. Formation of polyols by the lens of the rat with `Sugar' cataract. Nature, 1956, 184(4681), 194-195.
  4. Chalk, C.; Benstead, T.J.; Moore, F. Aldose reductase inhibitors for the treatment of diabetic polyneuropathy. Cochrane Libr., 2007, 2010(1), CD004572. doi: 10.1002/14651858.CD004572.pub2 PMID: 17943821
  5. Kinoshita, J.H.; Dvornik, D.; Kramil, M.; Gabbay, K.H. The effect of an aldose reductase inhibitor on the galactose-exposed rabbit lens. Biochim. Biophys. Acta, Gen. Subj., 1968, 158(3), 472-475. doi: 10.1016/0304-4165(68)90305-X PMID: 5660111
  6. Kinoshita, J.H.; Fukushi, S.; Kador, P.; Merola, L.O. Aldose reductase in diabetic complications of the eye. Metabolism, 1979, 28(4)(Suppl. 1), 462-469. doi: 10.1016/0026-0495(79)90057-X PMID: 45423
  7. Brownlee, M.; Cerami, A. The biochemistry of the complications of diabetes mellitus. Annu. Rev. Biochem., 1981, 50(1), 385-432. doi: 10.1146/annurev.bi.50.070181.002125 PMID: 6168237
  8. Stribling, D.; Armstrong, F.M.; Harrison, H.E. Aldose reductase in the etiology of diabetic complications: 2. Nephropathy. J. Diabet. Complications, 1989, 3(2), 70-76. doi: 10.1016/0891-6632(89)90015-9 PMID: 2526143
  9. Srivastava, S.K.; Ramana, K.V.; Bhatnagar, A. Role of aldose reductase and oxidative damage in diabetes and the consequent potential for therapeutic options. Endocr. Rev., 2005, 26(3), 380-392. doi: 10.1210/er.2004-0028 PMID: 15814847
  10. Schemmel, K.E.; Padiyara, R.S.; D’Souza, J.J. Aldose reductase inhibitors in the treatment of diabetic peripheral neuropathy: A review. J. Diabetes Complications, 2010, 24(5), 354-360. doi: 10.1016/j.jdiacomp.2009.07.005 PMID: 19748287
  11. Yamaoka, T.; Nishimura, C.; Yamashita, K.; Itakura, M.; Yamada, T.; Fujimoto, J.; Kokai, Y. Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA. Diabetologia, 1995, 38(3), 255-261. doi: 10.1007/BF00400627 PMID: 7758869
  12. Shah, V.O.; Scavini, M.; Nikolic, J.; Sun, Y.; Vai, S.; Griffith, J.K.; Dorin, R.I.; Stidley, C.; Yacoub, M.; Vander Jagt, D.L.; Eaton, R.P.; Zager, P.G. Z-2 microsatellite allele is linked to increased expression of the aldose reductase gene in diabetic nephropathy. J. Clin. Endocrinol. Metab., 1998, 83(8), 2886-2891. doi: 10.1210/jc.83.8.2886 PMID: 9709964
  13. Hodgkinson, A.D.; Søndergaard, K.L.; Yang, B.; Cross, D.F.; Millward, B.A.; Demaine, A.G. Aldose reductase expression is induced by hyperglycemia in diabetic nephropathy. Kidney Int., 2001, 60(1), 211-218. doi: 10.1046/j.1523-1755.2001.00788.x PMID: 11422753
  14. Ramana, K.V.; Chandra, D.; Wills, N.K.; Bhatnagar, A.; Srivastava, S.K. Oxidative stress-induced up-regulation of the chloride channel and Na+/Ca2+ exchanger during cataractogenesis in diabetic rats. J. Diabetes Complications, 2004, 18(3), 177-182. doi: 10.1016/S1056-8727(03)00003-5 PMID: 15145331
  15. Bhatnagar, A.; Ansari, N.H.; Zacarias, A.; Srivastava, S.K. Digital image analysis of cultured rat lens during oxidative stress-induced cataractogenesis. Exp. Eye Res., 1993, 57(4), 385-391. doi: 10.1006/exer.1993.1139 PMID: 8282024
  16. Srivastava, S.K.; Hair, G.A.; Das, B. Activated and unactivated forms of human erythrocyte aldose reductase. Proc. Natl. Acad. Sci. USA, 1985, 82(21), 7222-7226. doi: 10.1073/pnas.82.21.7222 PMID: 3933003
  17. Borhani, D.W.; Harter, T.M.; Petrash, J.M. The crystal structure of the aldose reductase.NADPH binary complex. J. Biol. Chem., 1992, 267(34), 24841-24847. doi: 10.1016/S0021-9258(18)35840-X PMID: 1447221
  18. Del-Corso, A.; Balestri, F.; Di Bugno, E.; Moschini, R.; Cappiello, M.; Sartini, S.; La-Motta, C.; Da-Settimo, F.; Mura, U. A new approach to control the enigmatic activity of aldose reductase. PLoS One, 2013, 8(9), e74076. doi: 10.1371/journal.pone.0074076 PMID: 24019949
  19. bander Jagt, D.L.; Kolb, N.S.; bander Jagt, T.J.; Chino, J.; Martinez, F.J.; Hunsaker, L.A.; Royer, R.E. Substrate specificity of human aldose reductase: Identification of 4-hydroxynonenal as an endogenous substrate. Biochim. Biophys. Acta Protein Struct. Mol. Enzymol., 1995, 1249(2), 117-126. doi: 10.1016/0167-4838(95)00021-L
  20. Dixit, B.L.; Balendiran, G.K.; Watowich, S.J.; Srivastava, S.; Ramana, K.V.; Petrash, J.M.; Bhatnagar, A.; Srivastava, S.K. Kinetic and structural characterization of the glutathione-binding site of aldose reductase. J. Biol. Chem., 2000, 275(28), 21587-21595. doi: 10.1074/jbc.M909235199 PMID: 10764810
  21. Ramana, K.V.; Chandra, D.; Srivastava, S.; Bhatnagar, A.; Aggarwal, B.B.; Srivastava, S.K. Aldose reductase mediates mitogenic signaling in vascular smooth muscle cells. J. Biol. Chem., 2002, 277(35), 32063-32070. doi: 10.1074/jbc.M202126200 PMID: 12063254
  22. Tammali, R.; Ramana, K.V.; Singhal, S.S.; Awasthi, S.; Srivastava, S.K. Aldose reductase regulates growth factor-induced cyclooxygenase-2 expression and prostaglandin E2 production in human colon cancer cells. Cancer Res., 2006, 66(19), 9705-9713. doi: 10.1158/0008-5472.CAN-06-2105 PMID: 17018629
  23. Ramasamy, R.; Goldberg, I.J. Aldose reductase and cardiovascular diseases, creating human-like diabetic complications in an experimental model. Circ. Res., 2010, 106(9), 1449-1458. doi: 10.1161/CIRCRESAHA.109.213447 PMID: 20466987
  24. Yadav, U.C.S.; Srivastava, S.K.; Ramana, K.V. Understanding the role of aldose reductase in ocular inflammation. Curr. Mol. Med., 2010, 10(6), 540-549. PMID: 20642441
  25. Cheng, H.M.; González, R.G. The effect of high glucose and oxidative stress on lens metabolism, aldose reductase, and senile cataractogenesis. Metabolism, 1986, 35(4)(Suppl. 1), 10-14. doi: 10.1016/0026-0495(86)90180-0 PMID: 3083198
  26. Trueblood, N.; Ramasamy, R. Aldose reductase inhibition improves altered glucose metabolism of isolated diabetic rat hearts. Am. J. Physiol., 1998, 275(1), H75-H83. PMID: 9688898
  27. Ido, Y.; Chang, K.; Woolsey, T.A.; Williamson, J.R. NADH: Sensor of blood flow need in brain, muscle, and other tissues. FASEB J., 2001, 15(8), 1419-1421. doi: 10.1096/fj.00-0652fje PMID: 11387243
  28. Williamson, J.R.; Chang, K.; Frangos, M.; Hasan, K.S.; Ido, Y.; Kawamura, T.; Nyengaard, J.R.; Den Enden, M.; Kilo, C.; Tilton, R.G. Hyperglycemic pseudohypoxia and diabetic complications. Diabetes, 1993, 42(6), 801-813. doi: 10.2337/diab.42.6.801 PMID: 8495803
  29. Jannapureddy, S.; Sharma, M.; Yepuri, G.; Schmidt, A.M.; Ramasamy, R. Aldose reductase: An emerging target for development of interventions for diabetic cardiovascular complications. Front. Endocrinol. (Lausanne), 2021, 12, 636267. doi: 10.3389/fendo.2021.636267 PMID: 33776930
  30. Tanimoto, T.; Maekawa, K.; Okada, S.; Yabe-Nishimura, C. Clinical analysis of aldose reductase for differential diagnosis of the pathogenesis of diabetic complication. Anal. Chim. Acta, 1998, 365(1-3), 285-292. doi: 10.1016/S0003-2670(97)00649-1
  31. Markus, H.B.; Raducha, M.; Harris, H. Tissue distribution of mammalian aldose reductase and related enzymes. Biochem. Med., 1983, 29(1), 31-45. doi: 10.1016/0006-2944(83)90051-0 PMID: 6404249
  32. Hashimoto, Y.; Yamagishi, S.I.; Mizukami, H.; Yabe-Nishimura, C.; Lim, S.W.; Kwon, H.M.; Yagihashi, S. Polyol pathway and diabetic nephropathy revisited: Early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase. J. Diabetes Investig., 2011, 2(2), 111-122. doi: 10.1111/j.2040-1124.2010.00071.x PMID: 24843470
  33. MacGregor, L.C.; Rosecan, L.R.; Laties, A.M.; Matschinsky, F.M. Altered retinal metabolism in diabetes. I. Microanalysis of lipid, glucose, sorbitol, and myo-inositol in the choroid and in the individual layers of the rabbit retina. J. Biol. Chem., 1986, 261(9), 4046-4051. doi: 10.1016/S0021-9258(17)35619-3 PMID: 3949802
  34. Frank, R.N. The aldose reductase controversy. Diabetes, 1994, 43(2), 169-172. doi: 10.2337/diab.43.2.169 PMID: 8288039
  35. Ramana, K.V.; Dixit, B.L.; Srivastava, S.; Bhatnagar, A.; Balendiran, G.K.; Watowich, S.J.; Petrash, J.M.; Srivastava, S.K. Characterization of the glutathione binding site of aldose reductase. Chem. Biol. Interact., 2001, 130-132(1-3), 537-548. doi: 10.1016/S0009-2797(00)00297-0 PMID: 11306073
  36. Ramana, K.V.; Dixit, B.L.; Srivastava, S.; Balendiran, G.K.; Srivastava, S.K.; Bhatnagar, A. Selective recognition of glutathiolated aldehydes by aldose reductase. Biochemistry, 2000, 39(40), 12172-12180. doi: 10.1021/bi000796e PMID: 11015195
  37. Pandey, S.; Srivastava, S.K.; Ramana, K.V. A potential therapeutic role for aldose reductase inhibitors in the treatment of endotoxin-related inflammatory diseases. Expert Opin. Investig. Drugs, 2012, 21(3), 329-339. doi: 10.1517/13543784.2012.656198 PMID: 22283786
  38. Chang, K.C.; Ponder, J.; LaBarbera, D.V.; Petrash, J.M. Aldose reductase inhibition prevents endotoxin-induced inflammatory responses in retinal microglia. Invest. Ophthalmol. Vis. Sci., 2014, 55(5), 2853-2861. doi: 10.1167/iovs.13-13487 PMID: 24677107
  39. Sato, S.; Lin, L.R.; Reddy, V.N.; Kador, P.F. Aldose reductase in human retinal pigment epithelial cells. Exp. Eye Res., 1993, 57(2), 235-241. doi: 10.1006/exer.1993.1119 PMID: 8405190
  40. Ramana, K.V.; Reddy, A.B.M.; Tammali, R.; Srivastava, S.K. Aldose reductase mediates endotoxin-induced production of nitric oxide and cytotoxicity in murine macrophages. Free Radic. Biol. Med., 2007, 42(8), 1290-1302. doi: 10.1016/j.freeradbiomed.2007.01.033 PMID: 17382209
  41. Tang, W.H.; Stitham, J.; Jin, Y.; Liu, R.; Lee, S.H.; Du, J.; Atteya, G.; Gleim, S.; Spollett, G.; Martin, K.; Hwa, J. Aldose reductase-mediated phosphorylation of p53 leads to mitochondrial dysfunction and damage in diabetic platelets. Circulation, 2014, 129(15), 1598-1609. doi: 10.1161/CIRCULATIONAHA.113.005224 PMID: 24474649
  42. Miwa, K.; Nakamura, J.; Hamada, Y.; Naruse, K.; Nakashima, E.; Kato, K.; Kasuya, Y.; Yasuda, Y.; Kamiya, H.; Hotta, N. The role of polyol pathway in glucose-induced apoptosis of cultured retinal pericytes. Diabetes Res. Clin. Pract., 2003, 60(1), 1-9. doi: 10.1016/S0168-8227(02)00248-6 PMID: 12639759
  43. Murata, M.; Ohta, N.; Sakurai, S.; Alam, S.; Tsai, J.Y.; Kador, P.F.; Sato, S. The role of aldose reductase in sugar cataract formation: Aldose reductase plays a key role in lens epithelial cell death (apoptosis). Chem. Biol. Interact., 2001, 130-132(1-3), 617-625. doi: 10.1016/S0009-2797(00)00289-1 PMID: 11306080
  44. Srivastava, S.; Ramana, K.V.; Tammali, R.; Srivastava, S.K.; Bhatnagar, A. Contribution of aldose reductase to diabetic hyperproliferation of vascular smooth muscle cells. Diabetes, 2006, 55(4), 901-910. doi: 10.2337/diabetes.55.04.06.db05-0932 PMID: 16567509
  45. Tesfamariam, B.; Palacino, J.J.; Weisbrod, R.M.; Cohen, R.A. Aldose reductase inhibition restores endothelial cell function in diabetic rabbit aorta. J. Cardiovasc. Pharmacol., 1993, 21(2), 205-211. doi: 10.1097/00005344-199302000-00004 PMID: 7679153
  46. Ramana, K.V.; Bhatnagar, A.; Srivastava, S.K. Aldose reductase regulates TNF-α-induced cell signaling and apoptosis in vascular endothelial cells. FEBS Lett., 2004, 570(1-3), 189-194. doi: 10.1016/j.febslet.2004.06.046 PMID: 15251463
  47. Ramana, K.V.; Friedrich, B.; Tammali, R.; West, M.B.; Bhatnagar, A.; Srivastava, S.K. Requirement of aldose reductase for the hyperglycemic activation of protein kinase C and formation of diacylglycerol in vascular smooth muscle cells. Diabetes, 2005, 54(3), 818-829. doi: 10.2337/diabetes.54.3.818 PMID: 15734861
  48. Ramana, K.V.; Friedrich, B.; Srivastava, S.; Bhatnagar, A.; Srivastava, S.K. Activation of nuclear factor-kappaB by hyperglycemia in vascular smooth muscle cells is regulated by aldose reductase. Diabetes, 2004, 53(11), 2910-2920. doi: 10.2337/diabetes.53.11.2910 PMID: 15504972
  49. Tammali, R.; Saxena, A.; Srivastava, S.K.; Ramana, K.V. Aldose reductase regulates vascular smooth muscle cell proliferation by modulating G1/S phase transition of cell cycle. Endocrinology, 2010, 151(5), 2140-2150. doi: 10.1210/en.2010-0160 PMID: 20308528
  50. Ramana, K.V.; Tammali, R.; Srivastava, S.K. Inhibition of aldose reductase prevents growth factor-induced G1-S phase transition through the AKT/phosphoinositide 3-kinase/E2F-1 pathway in human colon cancer cells. Mol. Cancer Ther., 2010, 9(4), 813-824. doi: 10.1158/1535-7163.MCT-09-0795 PMID: 20354121
  51. Reddy, A.B.M.; Ramana, K.V.; Srivastava, S.; Bhatnagar, A.; Srivastava, S.K. Aldose reductase regulates high glucose-induced ectodomain shedding of tumor necrosis factor (TNF)-α via protein kinase C-δ and TNF-α converting enzyme in vascular smooth muscle cells. Endocrinology, 2009, 150(1), 63-74. doi: 10.1210/en.2008-0677 PMID: 18772236
  52. Ramana, K.V.; Tammali, R.; Reddy, A.B.M.; Bhatnagar, A.; Srivastava, S.K. Aldose reductase-regulated tumor necrosis factor-alpha production is essential for high glucose-induced vascular smooth muscle cell growth. Endocrinology, 2007, 148(9), 4371-4384. doi: 10.1210/en.2007-0512 PMID: 17584970
  53. Wu, M.Y.; Yiang, G.T.; Lai, T.T.; Li, C.J. The oxidative stress and mitochondrial dysfunction during the pathogenesis of diabetic retinopathy. Oxid. Med. Cell. Longev., 2018, 2018, 1-12. doi: 10.1155/2018/3420187 PMID: 30254714
  54. Shukla, K.; Sonowal, H.; Saxena, A.; Ramana, K.V.; Srivastava, S.K. Aldose reductase inhibitor, fidarestat regulates mitochondrial biogenesis via Nrf2/HO-1/AMPK pathway in colon cancer cells. Cancer Lett., 2017, 411, 57-63. doi: 10.1016/j.canlet.2017.09.031 PMID: 28986187
  55. Szaflik, J.P.; Majsterek, I.; Kowalski, M.; Rusin, P.; Sobczuk, A.; Borucka, A.I.; Szaflik, J.; Blasiak, J. Association between sorbitol dehydrogenase gene polymorphisms and type 2 diabetic retinopathy. Exp. Eye Res., 2008, 86(4), 647-652. doi: 10.1016/j.exer.2008.01.009 PMID: 18289528
  56. Ellis, E.A.; Guberski, D.L.; Hutson, B.; Grant, M.B. Time course of NADH oxidase, inducible nitric oxide synthase and peroxynitrite in diabetic retinopathy in the BBZ/WOR rat. Nitric Oxide, 2002, 6(3), 295-304. doi: 10.1006/niox.2001.0419 PMID: 12009847
  57. Perkins, T.N.; Donnell, M.L.; Oury, T.D. The axis of the receptor for advanced glycation endproducts in asthma and allergic airway disease. Allergy, 2021, 76(5), 1350-1366. doi: 10.1111/all.14600 PMID: 32976640
  58. Dharmage, S.C.; Perret, J.L.; Custovic, A. Epidemiology of Asthma in Children and Adults. Front Pediatr., 2019, 7, 246. doi: 10.3389/fped.2019.00246 PMID: 31275909
  59. Murphy, D.M.; O’Byrne, P.M. Recent advances in the pathophysiology of asthma. Chest, 2010, 137(6), 1417-1426. doi: 10.1378/chest.09-1895 PMID: 20525652
  60. Yadav, U.C.S.; Naura, A.S.; Aguilera-Aguirre, L.; Boldogh, I.; Boulares, H.A.; Calhoun, W.J.; Ramana, K.V.; Srivastava, S.K. Aldose reductase inhibition prevents allergic airway remodeling through PI3K/AKT/GSK3β pathway in mice. PLoS One, 2013, 8(2), e57442. doi: 10.1371/journal.pone.0057442 PMID: 23460857
  61. Yadav, U.C.S.; Naura, A.S.; Aguilera-Aguirre, L.; Ramana, K.V.; Boldogh, I.; Sur, S.; Boulares, H.A.; Srivastava, S.K. Aldose reductase inhibition suppresses the expression of Th2 cytokines and airway inflammation in ovalbumin-induced asthma in mice. J. Immunol., 2009, 183(7), 4723-4732. doi: 10.4049/jimmunol.0901177 PMID: 19752229
  62. Wu, J.; Jin, Z.; Yan, L.J. Redox imbalance and mitochondrial abnormalities in the diabetic lung. Redox Biol., 2017, 11, 51-59. doi: 10.1016/j.redox.2016.11.003 PMID: 27888691
  63. Einarson, T.R.; Acs, A.; Ludwig, C.; Panton, U.H. Prevalence of cardiovascular disease in type 2 diabetes: A systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc. Diabetol., 2018, 17(1), 83. doi: 10.1186/s12933-018-0728-6 PMID: 29884191
  64. Son, N.H.; Ananthakrishnan, R.; Yu, S.; Khan, R.S.; Jiang, H.; Ji, R.; Akashi, H.; Li, Q.; O’Shea, K.; Homma, S.; Goldberg, I.J.; Ramasamy, R. Cardiomyocyte aldose reductase causes heart failure and impairs recovery from ischemia. PLoS One, 2012, 7(9), e46549. doi: 10.1371/journal.pone.0046549 PMID: 23029549
  65. Lim, W.F.; Forouhan, M.; Roberts, T.C.; Dabney, J.; Ellerington, R.; Speciale, A.A.; Manzano, R.; Lieto, M.; Sangha, G.; Banerjee, S.; Conceição, M.; Cravo, L.; Biscans, A.; Roux, L.; Pourshafie, N.; Grunseich, C.; Duguez, S.; Khvorova, A.; Pennuto, M.; Cortes, C.J.; La Spada, A.R.; Fischbeck, K.H.; Wood, M.J.A.; Rinaldi, C. Gene therapy with AR isoform 2 rescues spinal and bulbar muscular atrophy phenotype by modulating AR transcriptional activity. Sci. Adv., 2021, 7(34), eabi6896. doi: 10.1126/sciadv.abi6896 PMID: 34417184
  66. Balestri, F.; Moschini, R.; Mura, U.; Cappiello, M.; Del Corso, A. In search of differential inhibitors of aldose reductase. Biomolecules, 2022, 12(4), 485. doi: 10.3390/biom12040485 PMID: 35454074
  67. Julius, A.; Renuka, R.R.; Hopper, W.; Babu Raghu, P.; Rajendran, S.; Srinivasan, S.; Dharmalingam, K.; Alanazi, A.M.; Arokiyaraj, S.; Prasath, S. Inhibition of aldose reductase by novel phytocompounds: A heuristic approach to treating diabetic retinopathy. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-10. doi: 10.1155/2022/9624118 PMID: 35356240
  68. Grewal, A.S.; Thapa, K.; Kanojia, N.; Sharma, N.; Singh, S. Natural compounds as source of aldose reductase (AR) inhibitors for the treatment of diabetic complications: A mini review. Curr. Drug Metab., 2020, 21(14), 1091-1116. doi: 10.2174/1389200221666201016124125 PMID: 33069193
  69. Ansari, P.; Choudhury, S.T.; Seidel, V.; Rahman, A.B.; Aziz, M.A.; Richi, A.E.; Rahman, A.; Jafrin, U.H.; Hannan, J.M.A.; Abdel-Wahab, Y.H.A. Therapeutic potential of quercetin in the management of type-2 diabetes mellitus. Life (Basel), 2022, 12(8), 1146. doi: 10.3390/life12081146 PMID: 36013325
  70. Abhary, S.; Burdon, K.P.; Laurie, K.J.; Thorpe, S.; Landers, J.; Goold, L.; Lake, S.; Petrovsky, N.; Craig, J.E. Aldose reductase gene polymorphisms and diabetic retinopathy susceptibility. Diabetes Care, 2010, 33(8), 1834-1836. doi: 10.2337/dc09-1893 PMID: 20424224

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2024 Bentham Science Publishers