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image of Potential Role of Natural Oil in the Management of Diabetic Neuropathy- A Review

Abstract

Introduction

Diabetic neuropathy (DN) is a common complication of diabetes with limited therapeutic options. Given its complex pathophysiology involving oxidative stress, inflammation, and impaired nerve function, there is increasing interest in complementary therapies. This review aims to summarize the potential use of natural oils, both as dietary supplements and topical agents, for the prevention and management of DN.

Methods

A systematic literature search was conducted using databases such as SciFinder and PubMed for studies published from 1988 to January 2024. The search employed keywords including “diabetic neuropathy,” “natural oils,” and “bioactive constituents.” Relevant studies involving preclinical and clinical evaluation of natural oils or their active compounds in DN were selected, analyzed, and categorized based on the type of oil, mode of application, and mechanism of action.

Results

Several natural oils of plant and animal origin demonstrated protective and therapeutic effects against DN in both animal models and limited clinical settings. Their beneficial effects were attributed to anti-inflammatory and antioxidant properties, enhanced nerve conduction velocity, and modulation of vascular and neurotrophic factors. Both oral and topical applications contributed to symptom improvement.

Discussion

Due to the involvement of various signalling pathways and complex pathophysiology, DN has long been a condition with few acceptable treatment options. Although several natural oils have demonstrated activity against DN, very few clinical studies have been conducted to explore their therapeutic potential fully.

Conclusion

Natural oils represent a potential complementary strategy for managing DN. However, more rigorous clinical investigations are essential to confirm their safety, efficacy, and translational value.

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2025-09-24
2026-03-03
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References

  1. Sen S. Chakraborty R. De B. Diabetes Mellitus in 21st Century. Singapore Springer 2016 10.1007/978‑981‑10‑1542‑7
    [Google Scholar]
  2. Waller D.G. Sampson A.P. Renwick A.G. Hillier K. . 4th Ed. Amsterdam, Netherlands: Elsevier 2014; pp. 457-72 2014
    [Google Scholar]
  3. Cernea S. Raz I. Management of diabetic neuropathy. Metabolism 2021 123 154867 10.1016/j.metabol.2021.154867 34411554
    [Google Scholar]
  4. Selvarajah D. Sloan G. Tesfaye S. Diabetic neuropathy. The Foot in Diabetes. Sheffield, UK University of Sheffield 2020 89 103 10.1002/9781119445821.ch5
    [Google Scholar]
  5. Pop-Busui R. Boulton A.J.M. Feldman E.L. Diabetic neuropathy: A position statement by the american diabetes association. Diabetes Care 2017 40 1 136 154 10.2337/dc16‑2042 27999003
    [Google Scholar]
  6. Feldman E.L. Callaghan B.C. Pop-Busui R. Diabetic neuropathy. Nat. Rev. Dis. Primers 2019 5 1 41 10.1038/s41572‑019‑0092‑1 31197153
    [Google Scholar]
  7. Naseri R. Farzaei F. Fakhri S. Polyphenols for diabetes associated neuropathy: Pharmacological targets and clinical perspective. Daru 2019 27 2 781 798 10.1007/s40199‑019‑00289‑w 31352568
    [Google Scholar]
  8. Yang X.D. Fang P.F. Xiang D.X. Yang Y.Y. Topical treatments for diabetic neuropathic pain. Review Exp. Ther. Med. 2019 17 3 1963 1976 10.3892/etm.2019.7173 30783472
    [Google Scholar]
  9. Ardeleanu V. Toma A. Pafili K. Current pharmacological treatment of painful diabetic neuropathy: A narrative review. Medicina 2020 56 1 25 10.3390/medicina56010025 31936646
    [Google Scholar]
  10. Dworkin R.H. Jensen M.P. Gammaitoni A.R. Olaleye D.O. Galer B.S. Symptom profiles differ in patients with neuropathic versus non-neuropathic pain. J. Pain 2007 8 2 118 126 10.1016/j.jpain.2006.06.005 16949878
    [Google Scholar]
  11. Goldstein D.J. Lu Y. Detke M.J. Lee T.C. Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain 2005 116 1 109 118 10.1016/j.pain.2005.03.029 15927394
    [Google Scholar]
  12. Montvale N.J. PDR for Herbal Medicines. Montvale, N.J. Medical Economics Company 2002
    [Google Scholar]
  13. Ansari S.H. Chauhan B. Kumar G. Kalam N. Current concepts and prospects of herbal nutraceutical: A review. J. Adv. Pharm. Technol. Res. 2013 4 1 4 8 10.4103/2231‑4040.107494 23662276
    [Google Scholar]
  14. Majaz Q. Khurshid M.I. Nazim S. Asir Q. Shoeb Q. Neutraceuticals: Importance and advances in medicine and health. Int Res J Pharm 2012 3 4 71 73
    [Google Scholar]
  15. Sharma M. Majumdar P.K. Occupational lifestyle diseases: An emerging issue. Indian J. Occup. Environ. Med. 2009 13 3 109 112 10.4103/0019‑5278.58912 20442827
    [Google Scholar]
  16. Keen H. Payan J. Allawi J. Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-Linolenic Acid Multicenter Trial Group. Diabetes Care 1993 16 1 8 15 10.2337/diacare.16.1.8 8380765
    [Google Scholar]
  17. Yorek M.A. The potential role of fatty acids in treating diabetic neuropathy. Curr. Diab. Rep. 2018 18 10 86 10.1007/s11892‑018‑1046‑9 30145729
    [Google Scholar]
  18. Musharraf M.U. Ahmad Z. Yaqub Z. Comparison of topical capsaicin and topical turpentine Oil for treatment of painful diabetic neuropathy. J. Ayub Med. Coll. Abbottabad 2017 29 3 384 387 29076666
    [Google Scholar]
  19. Halat K.M. Dennehy C.E. Botanicals and dietary supplements in diabetic peripheral neuropathy. J. Am. Board Fam. Med. 2003 16 1 47 57 10.3122/jabfm.16.1.47 12583650
    [Google Scholar]
  20. Khalil H. Painful diabetic neuropathy management. Int. J. Evid.-Based Healthc. 2013 11 1 77 79 10.1111/1744‑1609.12010 23448333
    [Google Scholar]
  21. Yorek M.A. Is fish oil a potential treatment for diabetic peripheral neuropathy? Curr. Diabetes Rev. 2018 14 4 339 349 10.2174/1573399813666170522155327 28530530
    [Google Scholar]
  22. Bhattacharjee N. Barma S. Konwar N. Dewanjee S. Manna P. Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update. Eur. J. Pharmacol. 2016 791 8 24 10.1016/j.ejphar.2016.08.022 27568833
    [Google Scholar]
  23. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001 414 6865 813 820 10.1038/414813a 11742414
    [Google Scholar]
  24. Lee A.W. Chung S.S.M. Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J. 1999 13 1 23 30 10.1096/fasebj.13.1.23 9872926
    [Google Scholar]
  25. Tomlinson D.R. Gardiner N.J. Glucose neurotoxicity. Nat. Rev. Neurosci. 2008 9 1 36 45 10.1038/nrn2294 18094705
    [Google Scholar]
  26. Zochodne D.W. Diabetes mellitus and the peripheral nervous system: Manifestations and mechanisms. Muscle Nerve 2007 36 2 144 166 10.1002/mus.20785 17469109
    [Google Scholar]
  27. Zenker J. Ziegler D. Chrast R. Novel pathogenic pathways in diabetic neuropathy. Trends Neurosci. 2013 36 8 439 449 10.1016/j.tins.2013.04.008 23725712
    [Google Scholar]
  28. Agthong S. Tomlinson D.R. Inhibition of p38 MAP kinase corrects biochemical and neurological deficits in experimental diabetic neuropathy. Ann. N. Y. Acad. Sci. 2002 973 1 359 362 10.1111/j.1749‑6632.2002.tb04665.x 12485893
    [Google Scholar]
  29. Ramos K.M. Jiang Y. Svensson C.I. Calcutt N.A. Pathogenesis of spinally mediated hyperalgesia in diabetes. Diabetes 2007 56 6 1569 1576 10.2337/db06‑1269 17287466
    [Google Scholar]
  30. Obrosova I.G. Pacher P. Szabó C. Aldose reductase inhibition counteracts oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation in tissue sites for diabetes complications. Diabetes 2005 54 1 234 242 10.2337/diabetes.54.1.234 15616034
    [Google Scholar]
  31. Greene D.A. Lattimer S. Ulbrecht J. Carroll P. Glucose-induced alterations in nerve metabolism: Current perspective on the pathogenesis of diabetic neuropathy and future directions for research and therapy. Diabetes Care 1985 8 3 290 299 10.2337/diacare.8.3.290 2988888
    [Google Scholar]
  32. Khanra R. Dewanjee S.K. Dua T. Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response. J. Transl. Med. 2015 13 1 6 10.1186/s12967‑014‑0364‑1 25591455
    [Google Scholar]
  33. Veves A. King G.L. Can VEGF reverse diabetic neuropathy in human subjects? J. Clin. Invest. 2001 107 10 1215 1218 10.1172/JCI13038 11375408
    [Google Scholar]
  34. Xia Z. Dickens M. Raingeaud J. Davis R.J. Greenberg M.E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995 270 5240 1326 1331 10.1126/science.270.5240.1326 7481820
    [Google Scholar]
  35. Kolm-Litty V. Sauer U. Nerlich A. Lehmann R. Schleicher E.D. High glucose-induced transforming growth factor beta1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J. Clin. Invest. 1998 101 1 160 169 10.1172/JCI119875 9421478
    [Google Scholar]
  36. Sayeski P.P. Kudlow J.E. Glucose metabolism to glucosamine is necessary for glucose stimulation of transforming growth factor-alpha gene transcription. J. Biol. Chem. 1996 271 25 15237 15243 10.1074/jbc.271.25.15237 8663078
    [Google Scholar]
  37. Hirakata Y. Kitamura S. Elevated serum transforming growth factor 1 level in primary lung cancer patients with finger clubbing. Eur. J. Clin. Invest. 1996 26 9 820 823 10.1046/j.1365‑2362.1996.2260560.x 8889446
    [Google Scholar]
  38. Kaneto H. Xu G. Song K.H. Activation of the hexosamine pathway leads to deterioration of pancreatic beta-cell function through the induction of oxidative stress. J. Biol. Chem. 2001 276 33 31099 31104 10.1074/jbc.M104115200 11390407
    [Google Scholar]
  39. Baynes J.W. Role of oxidative stress in development of complications in diabetes. Diabetes 1991 40 4 405 412 10.2337/diab.40.4.405 2010041
    [Google Scholar]
  40. Matough F.A. Budin S.B. Hamid Z.A. Alwahaibi N. Mohamed J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ. Med. J. 2012 12 1 5 18 10.18295/2075‑0528.1334 22375253
    [Google Scholar]
  41. Casellini C.M. Vinik A.I. Recent advances in the treatment of diabetic neuropathy. Curr Opin Int Med 2006 5 3 260 266 10.1097/01.med.0000216963.51751.be
    [Google Scholar]
  42. Wang X. Mori T. Sumii T. Lo E.H. Hemoglobin-induced cytotoxicity in rat cerebral cortical neurons: Caspase activation and oxidative stress. Stroke 2002 33 7 1882 1888 10.1161/01.STR.0000020121.41527.5D 12105370
    [Google Scholar]
  43. Sekido H. Suzuki T. Jomori T. Takeuchi M. Yabe-Nishimura C. Yagihashi S. Reduced cell replication and induction of apoptosis by advanced glycation end products in rat Schwann cells. Biochem. Biophys. Res. Commun. 2004 320 1 241 248 10.1016/j.bbrc.2004.05.159 15207727
    [Google Scholar]
  44. Cameron N.E. Cotter M.A. Effects of evening primrose oil treatment on sciatic nerve blood flow and endoneurial oxygen tension in streptozotocin-diabetic rats. Acta Diabetol. 1994 31 4 220 225 10.1007/BF00571955 7888693
    [Google Scholar]
  45. Arnoult D. Rismanchi N. Grodet A. Bax/Bak-dependent release of DDP/TIMM8a promotes Drp1-mediated mitochondrial fission and mitoptosis during programmed cell death. Curr. Biol. 2005 15 23 2112 2118 10.1016/j.cub.2005.10.041 16332536
    [Google Scholar]
  46. Ramasamy R. Yan S.F. Schmidt A.M. Arguing for the motion: Yes, RAGE is a receptor for advanced glycation endproducts. Mol. Nutr. Food Res. 2007 51 9 1111 1115 10.1002/mnfr.200700008 17854009
    [Google Scholar]
  47. Liu X. Xu Y. An M. Zeng Q. The risk factors for diabetic peripheral neuropathy: A meta-analysis. PLoS One 2019 14 2 0212574 10.1371/journal.pone.0212574 30785930
    [Google Scholar]
  48. Lu Y. Xing P. Cai X. Prevalence and risk factors for diabetic peripheral neuropathy in type 2 diabetic patients from 14 countries: Estimates of the interpret-dd study. Front. Public Health 2020 8 534372 10.3389/fpubh.2020.534372 33194943
    [Google Scholar]
  49. Jamal G.A. The use of gamma linolenic acid in the prevention and treatment of diabetic neuropathy. Diabet. Med. 1994 11 2 145 149 10.1111/j.1464‑5491.1994.tb02010.x 8200197
    [Google Scholar]
  50. Horrobin D.F. A new concept of lifestyle-related cardiovascular disease: The importance of interactions between cholesterol, essential fatty acids, prostaglandin E1 and thromboxane A2. Med. Hypotheses 1980 6 8 785 800 10.1016/0306‑9877(80)90003‑1 7003328
    [Google Scholar]
  51. Horrobin D.F. The roles of essential fatty acids in the development of diabetic neuropathy and other complications of diabetes mellitus. Prostaglandins Leukot. Essent. Fatty Acids 1988 31 3 181 197 3047752
    [Google Scholar]
  52. Brenner R.R. Nutritional and hormonal factors influencing desaturation of essential fatty acids. Prog. Lipid Res. 1981 20 1 41 47 10.1016/0163‑7827(81)90012‑6 7342101
    [Google Scholar]
  53. Boberg M. Vessby B. Selinus I. Effects of dietary supplementation with n-6 and n-3 long-chain polyunsaturated fatty acids on serum lipoproteins and platelet function in hypertriglyceridaemic patients. Acta Med. Scand. 1986 220 2 153 160 10.1111/j.0954‑6820.1986.tb02743.x 3535392
    [Google Scholar]
  54. Jamal G. Carmichael H. Weir A.I. Gamma-linolenic acid in diabetic neuropathy. Lancet 1986 327 8489 1098 10.1016/S0140‑6736(86)91365‑6 2871365
    [Google Scholar]
  55. Takahashi R. Inoue J. Ito H. Hibino H. Evening primrose oil and fish oil in non-insulin-dependent-diabetes. Prostaglandins Leukot. Essent. Fatty Acids 1993 49 2 569 571 10.1016/0952‑3278(93)90162‑P 8415806
    [Google Scholar]
  56. Cameron N.E. Cotter M.A. Hohman T.C. Interactions between essential fatty acid, prostanoid, polyol pathway and nitric oxide mechanisms in the neurovascular deficit of diabetic rats. Diabetologia 1996 39 2 172 182 10.1007/BF00403960 8635669
    [Google Scholar]
  57. Carter J.P. Gamma-linolenic acid as a nutrient. Food Technol. 1988 42 6 72 82
    [Google Scholar]
  58. Julu P.O.O. Essential fatty acids prevent slowed nerve conduction in streptozotocin diabetic rats. J Diabet Compl 1988 2 4 185 188 10.1016/S0891‑6632(88)80006‑0 2853165
    [Google Scholar]
  59. Tomlinson D.R. Robinson J.P. Compton A.M. Keen P. Essential fatty acid treatment? effects on nerve conduction, polyol pathway and axonal transport in streptozotocin diabetic rats. Diabetologia 1989 32 9 655 659 10.1007/BF00274252 2477293
    [Google Scholar]
  60. Julu P.O.O. Mutamba A. Comparison of short-term effects of insulin and essential fatty acids on the slowed nerve conduction of streptozotocin diabetes in rats. J. Neurol. Sci. 1991 106 1 56 59 10.1016/0022‑510X(91)90194‑C 1663993
    [Google Scholar]
  61. Cameron N.E. Cotter M.A. Robertson S. Essential fatty acid diet supplementation. Effects on peripheral nerve and skeletal muscle function and capillarization in streptozocin-induced diabetic rats. Diabetes 1991 40 5 532 539 10.2337/diab.40.5.532 2022301
    [Google Scholar]
  62. Cameron N.E. Cotter M.A. Dines K.C. Robertson S. Cox D. The effects of evening primrose oil on nerve function and capillarization in streptozotocin diabetic rats: Modulation by the cyclo oxygenase inhibitor flurbiprofen. Br. J. Pharmacol. 1993 109 4 972 979 10.1111/j.1476‑5381.1993.tb13716.x 8401950
    [Google Scholar]
  63. Cameron N.E. Cotter M.A. The relationship of vascular changes to metabolic factors in diabetes mellitus and their role in the development of peripheral nerve complications. Diabetes Metab. Rev. 1994 10 3 189 224 10.1002/dmr.5610100302 7835170
    [Google Scholar]
  64. Omran O.M. Histopathological study of evening primrose oil effects on experimental diabetic neuropathy. Ultrastruct. Pathol. 2012 36 4 222 227 10.3109/01913123.2012.662268 22574767
    [Google Scholar]
  65. Dines K.C. Cameron N.E. Cotter M.A. Comparison of the effects of evening primrose oil and triglycerides containing gamma-linolenic acid on nerve conduction and blood flow in diabetic rats. J. Pharmacol. Exp. Ther. 1995 273 1 49 55 10.1016/S0022‑3565(25)09610‑7 7714803
    [Google Scholar]
  66. Dines K.C. Cotter M.A. Cameron N.E. Contrasting effects of treatment with w-3 and w-6 essential fatty acids on peripheral nerve function and capillarization in streptozotocin-diabetic ratsn. Diabetologia 1993 36 11 1132 1138 10.1007/BF00401057 8270127
    [Google Scholar]
  67. Coste T. Pierlovisi M. Leonardi J. Beneficial effects of gamma linolenic acid supplementation on nerve conduction velocity, Na+, K+ ATPase activity, and membrane fatty acid composition in sciatic nerve of diabetic rats. J. Nutr. Biochem. 1999 10 7 411 420 10.1016/S0955‑2863(99)00020‑0 15539317
    [Google Scholar]
  68. Dines K.C. Cotter M.A. Cameron N.E. Effectiveness of natural oils as sources of -linolenic acid to correct peripheral nerve conduction velocity abnormalities in diabetic rats: Modulation by thromboxane A2 inhibition. Prostaglandins Leukot. Essent. Fatty Acids 1996 55 3 159 165 10.1016/S0952‑3278(96)90092‑7 8931113
    [Google Scholar]
  69. Urlić M, Urlić I, Urlić H, et al. Effects of different n6/n3 PUFAs dietary ratio on cardiac diabetic neuropathy. Nutrients 2020 12 9 2761 10.3390/nu12092761 32927766
    [Google Scholar]
  70. Cotter M.A. Cameron N.E. Effects of dietary supplementation with arachidonic acid rich oils on nerve conduction and blood flow in streptozotocin-diabetic rats. Prostaglandins Leukot. Essent. Fatty Acids 1997 56 5 337 343 10.1016/S0952‑3278(97)90581‑0 9175169
    [Google Scholar]
  71. Gerbi A. Maixent J.M. Barbey O. Alterations of Na,K-ATPase isoenzymes in the rat diabetic neuropathy: Protective effect of dietary supplementation with n-3 fatty acids. J. Neurochem. 1998 71 2 732 740 10.1046/j.1471‑4159.1998.71020732.x 9681464
    [Google Scholar]
  72. Gerbi A. Sennoune S. Pierre S. Localization of Na,K-ATPase alpha/beta isoforms in rat sciatic nerves: Effect of diabetes and fish oil treatment. J. Neurochem. 1999 73 2 719 726 10.1046/j.1471‑4159.1999.0730719.x 10428069
    [Google Scholar]
  73. Coppey L.J. Holmes A. Davidson E.P. Yorek M.A. Partial replacement with menhaden oil improves peripheral neuropathy in high-fat-fed low-dose streptozotocin type 2 diabetic rat. J. Nutr. Metab. 2012 2012 1 1 8 10.1155/2012/950517 22988492
    [Google Scholar]
  74. Coppey L.J. Davidson E.P. Obrosov A. Yorek M.A. Enriching the diet with menhaden oil improves peripheral neuropathy in streptozotocin-induced type 1 diabetic rats. J. Neurophysiol. 2015 113 3 701 708 10.1152/jn.00718.2014 25376787
    [Google Scholar]
  75. Bazan N.G. Supply of n-3 polyunsaturated fatty acids and their significance in the central nervous system.In: Wurtman RJ, Wurtman JJ, Eds. Nutrition and the Brain. (1)1-22.
    [Google Scholar]
  76. Coste T.C. Gerbi A. Vague P. Pieroni G. Raccah D. Neuroprotective effect of docosahexaenoic acid-enriched phospholipids in experimental diabetic neuropathy. Diabetes 2003 52 10 2578 2585 10.2337/diabetes.52.10.2578 14514643
    [Google Scholar]
  77. Coppey L. Davidson E. Shevalye H. Obrosov A. Yorek M. Effect of early and late interventions with dietary oils on vascular and neural complications in a type 2 diabetic rat model. J. Diabetes Res. 2019 2019 1 1 12 10.1155/2019/5020465 31485451
    [Google Scholar]
  78. Coppey L. Davidson E. Shevalye H. Obrosov A. Torres M. Yorek M.A. Progressive loss of corneal nerve fibers and sensitivity in rats modeling obesity and type 2 diabetes is reversible with omega-3 fatty acid intervention: Supporting cornea analyses as a marker for peripheral neuropathy and treatment. Diabetes Metab. Syndr. Obes. 2020 13 1 1367 1384 10.2147/DMSO.S247571 32425569
    [Google Scholar]
  79. Serhan C.N. Clish C.B. Brannon J. Colgan S.P. Chiang N. Gronert K. Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J. Exp. Med. 2000 192 8 1197 1204 10.1084/jem.192.8.1197 11034610
    [Google Scholar]
  80. Serhan C.N. Hong S. Gronert K. Resolvins. J. Exp. Med. 2002 196 8 1025 1037 10.1084/jem.20020760 12391014
    [Google Scholar]
  81. Hong S. Gronert K. Devchand P.R. Moussignac R.L. Serhan C.N. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J. Biol. Chem. 2003 278 17 14677 14687 10.1074/jbc.M300218200 12590139
    [Google Scholar]
  82. Bannenberg G.L. Chiang N. Ariel A. Molecular circuits of resolution: Formation and actions of resolvins and protectins. J. Immunol. 2005 174 7 4345 4355 10.4049/jimmunol.174.7.4345 15778399
    [Google Scholar]
  83. Shevalye H. Yorek M.S. Coppey L.J. Effect of enriching the diet with menhaden oil or daily treatment with resolvin D1 on neuropathy in a mouse model of type 2 diabetes. J. Neurophysiol. 2015 114 1 199 208 10.1152/jn.00224.2015 25925322
    [Google Scholar]
  84. Obrosov A. Coppey L.J. Shevalye H. Yorek M.A. Effect of fish oil Vs. Resolvin D1, E1, methyl esters of resolvins d1 or d2 on diabetic peripheral neuropathy. J. Neurol. Neurophysiol. 2017 8 6 453 10.4172/2155‑9562.1000453 29423332
    [Google Scholar]
  85. Davidson E.P. Holmes A. Coppey L.J. Yorek M.A. Effect of combination therapy consisting of enalapril, -lipoic acid, and menhaden oil on diabetic neuropathy in a high fat/low dose streptozotocin treated rat. Eur. J. Pharmacol. 2015 765 1 258 267 10.1016/j.ejphar.2015.08.015 26291662
    [Google Scholar]
  86. Holmes A. Coppey L.J. Davidson E.P. Yorek M.A. Rat models of diet-induced obesity and high fat/low dose streptozotocin type 2 diabetes: Effect of reversal of high fat diet compared to treatment with enalapril or menhaden oil on glucose utilization and neuropathic endpoints. J. Diabetes Res. 2015 2015 1 8 10.1155/2015/307285 26229968
    [Google Scholar]
  87. Yorek M.S. Obrosov A. Shevalye H. Coppey L.J. Kardon R.H. Yorek M.A. Early vs. late intervention of high fat/low dose streptozotocin treated C57Bl/6J mice with enalapril, -lipoic acid, menhaden oil or their combination: Effect on diabetic neuropathy related endpoints. Neuropharmacology 2017 116 1 122 131 10.1016/j.neuropharm.2016.12.022 28025096
    [Google Scholar]
  88. Davidson E.P. Coppey L.J. Shevalye H. Obrosov A. Kardon R.H. Yorek M.A. Impaired corneal sensation and nerve loss in a type 2 rat model of chronic diabetes is reversible with combination therapy of menhaden oil, -lipoic acid, and enalapril. Cornea 2017 36 6 725 731 10.1097/ICO.0000000000001182 28476051
    [Google Scholar]
  89. Yorek M.S. Coppey L.J. Shevalye H. Obrosov A. Kardon R.H. Yorek M.A. Effect of treatment with salsalate, menhaden oil, combination of salsalate and menhaden oil, or resolvin D1 of C57BL/6J type 1 diabetic mouse on neuropathic endpoints. J. Nutr. Metab. 2016 2016 1 11 10.1155/2016/5905891 27774316
    [Google Scholar]
  90. Davidson EP Coppey LJ Shevalye H Obrosov A Yorek MA Effect of dietary content of menhaden oil with or without salsalate on neuropathic endpoints in High-Fat-Fed/Low-dose streptozotocin-treated sprague dawley rats. J Diabetes Res 2018 2018 1 1 9 10.1155/2018/2967127 30057911
    [Google Scholar]
  91. Nangle M. Gibson T. Cotter M. Cameron N. Effects of eugenol on nerve and vascular dysfunction in streptozotocin-diabetic rats. Planta Med. 2006 72 6 494 500 10.1055/s‑2005‑916262 16773532
    [Google Scholar]
  92. Bhatti R. Sukhmeet K. Jaswinder S. Mohan P.S.I. Ameliorative effect of volatile oil from Cinnamomum zeylanicum on hyperalgesia in alloxan diabetic rats. Can J Pure Appl Sci 2009 3 3 887 895
    [Google Scholar]
  93. Hasanein P. Riahi H. Antinociceptive and antihyperglycemic effects of Melissa officinalis essential oil in an experimental model of diabetes. Med. Princ. Pract. 2015 24 1 47 52 10.1159/000368755 25402675
    [Google Scholar]
  94. Silva-Alves K.S. Ferreira-da-Silva F.W. Coelho-de-Souza A.N. Leal-Cardoso J.H. Essential oil of Croton zehntneri prevents conduction alterations produced by diabetes mellitus on vagus nerve. Plants 2021 10 5 893 10.3390/plants10050893 33925228
    [Google Scholar]
  95. Pitel S. Raccah D. Gerbi A. Pieroni G. Vague P. Coste T.C. At low doses, a gamma-linolenic acid-lipoic acid conjugate is more effective than docosahexaenoic acid-enriched phospholipids in preventing neuropathy in diabetic rats. J. Nutr. 2007 137 2 368 372 10.1093/jn/137.2.368 17237313
    [Google Scholar]
  96. Russell J Feldman E. Insulin-like growth factor-I prevents apoptosis in sympathetic neurons exposed to high glucose. Horm Metab Res 1999 ;31(02/03): 90-6. 10.1055/s‑2007‑978704 10226787
    [Google Scholar]
  97. Russell J.W. Berent-Spillson A. Delaney C. Oxidative neuronal injury is associated with programmed cell death and neuropathy in an animal model of type II diabetes and impaired glucose tolerance. Ann. Neurol. 2002 52 S97 S7 10.1016/j.nbd.2008.02.013 18424057
    [Google Scholar]
  98. Hermenegildo C. Raya A. Romá J. Romero F.J. Decreased glutathione peroxidase activity in sciatic nerve of alloxan-induced diabetic mice and its correlation with blood glucose levels. Neurochem. Res. 1993 18 8 893 896 10.1007/BF00998274 8396737
    [Google Scholar]
  99. Anwar M.M. Meki A.R.M.A. Oxidative stress in streptozotocin-induced diabetic rats: Effects of garlic oil and melatonin. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2003 135 4 539 547 10.1016/S1095‑6433(03)00114‑4 12890544
    [Google Scholar]
  100. Hamdy N.M. Taha R.A. Effects of Nigella sativa oil and thymoquinone on oxidative stress and neuropathy in streptozotocin-induced diabetic rats. Pharmacology 2009 84 3 127 134 10.1159/000234466 19684436
    [Google Scholar]
  101. Ghatak S.B. Panchal S.S. Protective effect of oryzanol isolated from crude rice bran oil in experimental model of diabetic neuropathy. Rev. Bras. Farmacogn. 2012 22 5 1092 1103 10.1590/S0102‑695X2012005000104
    [Google Scholar]
  102. Ristagno G. Fumagalli F. Porretta-Serapiglia C. Hydroxytyrosol attenuates peripheral neuropathy in streptozotocin-induced diabetes in rats. J. Agric. Food Chem. 2012 60 23 5859 5865 10.1021/jf2049323 22594308
    [Google Scholar]
  103. Suribabu R.P. Saikiran S.S.T. Siddhartha V.C. Nageswararao P.S. Protective effect of hydroxytyrosol from diabetic peripheral neuropathy in rodents: Implications of antioxidant and anti-inflammatory effects. Lat. Am. J. Pharm. 2017 36 2 373 379
    [Google Scholar]
  104. Reddy M.A. Thimmalapura P.R. Lanting L. Nadler J.L. Fatima S. Natarajan R. The oxidized lipid and lipoxygenase product 12(S)-hydroxyeicosatetraenoic acid induces hypertrophy and fibronectin transcription in vascular smooth muscle cells via p38 MAPK and cAMP response element-binding protein activation. Mediation of angiotensin II effects. J. Biol. Chem. 2002 277 12 9920 9928 10.1074/jbc.M111305200 11786549
    [Google Scholar]
  105. Prasad S.N. Muralidhara. Protective effects of geraniol (a monoterpene) in a diabetic neuropathy rat model: Attenuation of behavioral impairments and biochemical perturbations. J. Neurosci. Res. 2014 92 9 1205 1216 10.1002/jnr.23393 24752916
    [Google Scholar]
  106. Fajrin F.A. Imandasari N. Barki T. The activity of red ginger oil in antioxidant study in vitro and antihyperalgesia effect in alloxan-induced painful diabetic neuropathy in mice. Thaiphesatchasan 2019 43 2 69 75 10.56808/3027‑7922.2422
    [Google Scholar]
  107. Gamila S.M. El-Saeed H.W. Maha E.L-W. Hoda A.M. Nabila E.L. Effect of fish oil on oxidative stress and monoamine of brain tissue in STZ mice. World J Med Sci 2013 8 4 401 407 10.5829/idosi.wjms.2013.8.4.74143
    [Google Scholar]
  108. Karasu Dewhurst.M. Stevens E.J. Tomlinson D.R. Effects of anti-oxidant treatment on sciatic nerve dysfunction in streptozotocin-diabetic rats; comparison with essential fatty acids. Diabetologia 1995 38 2 129 134 10.1007/BF00400086 7713308
    [Google Scholar]
  109. Ford I. Cotter M.A. Cameron N.E. Greaves M. The effects of treatment with [alpha]-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow, and peripheral nerve conduction in the streptozotocin-diabetic rat. Metabolism 2001 50 8 868 875 10.1053/meta.2001.24914 11474472
    [Google Scholar]
  110. Shotton H.R. Clarke S. Lincoln J. The effectiveness of treatments of diabetic autonomic neuropathy is not the same in autonomic nerves supplying different organs. Diabetes 2003 52 1 157 164 10.2337/diabetes.52.1.157 12502507
    [Google Scholar]
  111. Shotton H.R. Broadbent S. Lincoln J. Prevention and partial reversal of diabetes-induced changes in enteric nerves of the rat ileum by combined treatment with -lipoic acid and evening primrose oil. Auton. Neurosci. 2004 111 1 57 65 10.1016/j.autneu.2004.02.004 15109939
    [Google Scholar]
  112. Prabhakar O. Cerebroprotective effect of resveratrol through antioxidant and anti-inflammatory effects in diabetic rats. Naunyn Schmiedebergs Arch. Pharmacol. 2013 386 8 705 710 10.1007/s00210‑013‑0871‑2 23612842
    [Google Scholar]
  113. Kellogg A.P. Wiggin T.D. Larkin D.D. Hayes J.M. Stevens M.J. Pop-Busui R. Protective effects of cyclooxygenase-2 gene inactivation against peripheral nerve dysfunction and intraepidermal nerve fiber loss in experimental diabetes. Diabetes 2007 56 12 2997 3005 10.2337/db07‑0740 17720896
    [Google Scholar]
  114. Pop-Busui R. Marinescu V. Van Huysen C. Dissection of metabolic, vascular, and nerve conduction interrelationships in experimental diabetic neuropathy by cyclooxygenase inhibition and acetyl-L-carnitine administration. Diabetes 2002 51 8 2619 2628 10.2337/diabetes.51.8.2619 12145179
    [Google Scholar]
  115. Harris R.E. Cyclooxygenase-2 (cox-2) and the inflammogenesis of cancer. Subcell. Biochem. 2007 42 93 126 10.1007/1‑4020‑5688‑5_4 17612047
    [Google Scholar]
  116. Wu K.K. Inducible cyclooxygenase and nitric oxide synthase. Adv. Pharmacol. 1995 33 179 207 10.1016/S1054‑3589(08)60669‑9 7495670
    [Google Scholar]
  117. Kellogg A.P. Pop-Busui R. Peripheral nerve dysfunction in experimental diabetes is mediated by cyclooxygenase-2 and oxidative stress. Antioxid. Redox Signal. 2005 7 11-12 1521 1529 10.1089/ars.2005.7.1521 16356116
    [Google Scholar]
  118. Kühn H. O’Donnell V.B. Inflammation and immune regulation by 12/15-lipoxygenases. Prog. Lipid Res. 2006 45 4 334 356 10.1016/j.plipres.2006.02.003 16678271
    [Google Scholar]
  119. Natarajan R. Reddy M.A. Malik K.U. Fatima S. Khan B.V. Signaling mechanisms of nuclear factor-kappab-mediated activation of inflammatory genes by 13-hydroperoxyoctadecadienoic acid in cultured vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 2001 21 9 1408 1413 10.1161/hq0901.095278 11557664
    [Google Scholar]
  120. Reilly K.B. Srinivasan S. Hatley M.E. 12/15-Lipoxygenase activity mediates inflammatory monocyte/endothelial interactions and atherosclerosis in vivo. J. Biol. Chem. 2004 279 10 9440 9450 10.1074/jbc.M303857200 14676201
    [Google Scholar]
  121. Juju P.O.O. Gow J.W. Jamal G.A. Endogenous cyclo-oxygenase substrates mediate the neuroactivity of evening primrose oil in rats. J. Lipid Mediat. Cell Signal. 1996 13 2 115 125 10.1016/0929‑7855(95)00055‑0 8925193
    [Google Scholar]
  122. Li M.Y. Wang Y.Y. Cao R. Dietary fish oil inhibits mechanical allodynia and thermal hyperalgesia in diabetic rats by blocking nuclear factor- B-mediated inflammatory pathways. J. Nutr. Biochem. 2015 26 11 1147 1155 10.1016/j.jnutbio.2015.05.005 26118694
    [Google Scholar]
  123. Laubertová L Koňariková K, Gbelcová H, et al. Fish oil emulsion supplementation might improve quality of life of diabetic patients due to its antioxidant and anti-inflammatory properties. Nutr. Res. 2017 46 1 49 58 10.1016/j.nutres.2017.07.012 28893413
    [Google Scholar]
  124. Coppey L. Obrosov A. Shevalye H. Davidson E. Paradee W. Yorek M.A. Characterization of mice ubiquitously overexpressing human 15-lipoxygenase-1: Effect of diabetes on peripheral neuropathy and treatment with menhaden oil. J. Diabetes Res. 2021 2021 1 1 11 10.1155/2021/5564477 33816635
    [Google Scholar]
  125. Menon D. Lewis E.J.H. Perkins B.A. Bril V. Omega-3 nutrition therapy for the treatment of diabetic sensorimotor polyneuropathy. Curr. Diabetes Rev. 2022 18 5 010921196028 10.2174/1573399817666210901121111 34488588
    [Google Scholar]
  126. Durán A.M. Beeson W.L. Firek A. Cordero-MacIntyre Z. De León M. Dietary omega-3 polyunsaturated fatty-acid supplementation upregulates protective cellular pathways in patients with type 2 diabetes exhibiting improvement in painful diabetic neuropathy. Nutrients 2022 14 4 761 10.3390/nu14040761 35215418
    [Google Scholar]
  127. Sachan N. Saraswat N. Chandra P. Khalid M. Kabra A. Isolation of thymol from Trachyspermum ammi fruits for treatment of diabetes and diabetic neuropathy in STZ induced rats. BioMed Res. Int. 2022 2022 1 8263999 10.1155/2022/8263999 35528161
    [Google Scholar]
  128. Noventi I. Maimunah S. Hasina S.N. Putri R.A. Faizah I. Kartini Y. Essential oil for diabetic neuropathy pain. Front Health Inf 2024 13 3 7308 10.52783/fhi.vi.681
    [Google Scholar]
  129. Li L. The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial. BMC Complement. Altern. Med. 2010 10 1 22 10.1186/1472‑6882‑10‑22 20487567
    [Google Scholar]
  130. Heydari M. Homayouni K. Hashempur M.H. Shams M. TopicalC itrullus colocynthis (bitter apple) extract oil in painful diabetic neuropathy: A double blind randomized placebo controlled clinical trial. J. Diabetes 2016 8 2 246 252 10.1111/1753‑0407.12287 25800045
    [Google Scholar]
  131. Dewanjee S. Das S. Das A.K. Molecular mechanism of diabetic neuropathy and its pharmacotherapeutic targets. Eur. J. Pharmacol. 2018 833 472 523 10.1016/j.ejphar.2018.06.034 29966615
    [Google Scholar]
  132. Gok Metin Z. Arikan Donmez A. Izgu N. Ozdemir L. Arslan I.E. Aromatherapy massage for neuropathic pain and quality of life in diabetic patients. J. Nurs. Scholarsh. 2017 49 4 379 388 10.1111/jnu.12300 28605119
    [Google Scholar]
  133. Rivaz M. Rahpeima M. Khademian Z. Dabbaghmanesh M.H. The effects of aromatherapy massage with lavender essential oil] on neuropathic pain and quality of life in diabetic patients: A randomized clinical trial. Complement. Ther. Clin. Pract. 2021 44 101430 10.1016/j.ctcp.2021.101430 34217127
    [Google Scholar]
  134. Lewis E.J.H. Perkins B.A. Lovblom L.E. Bazinet R.P. Wolever T.M.S. Bril V. Effect of omega-3 supplementation on neuropathy in type 1 diabetes. Neurology 2017 88 24 2294 2301 10.1212/WNL.0000000000004033 28515269
    [Google Scholar]
  135. McLellan A. Homeopathic composition comprising hypericum perforatum extract and essential oils for the treatment of neuropathic pain. CA Patent 2743967A1, 2010. 2010
    [Google Scholar]
  136. Motilal S. Maharaj R.G. Nutmeg extracts for painful diabetic neuropathy: A randomized, double-blind, controlled study. J. Altern. Complement. Med. 2013 19 4 347 352 10.1089/acm.2012.0016 23098698
    [Google Scholar]
  137. Kyle D.J. Microbial oils containing arachidonic and docosahexaenoic acids for treating neurological disorders. Geneva, Switzerland World Intellectual Property Organization 1994
    [Google Scholar]
  138. Lewis E.J.H. Lovblom L.E. Cisbani G. Baseline omega-3 level is associated with nerve regeneration following 12-months of omega-3 nutrition therapy in patients with type 1 diabetes. J. Diabetes Complications 2021 35 3 107798 10.1016/j.jdiacomp.2020.107798 33309385
    [Google Scholar]
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