NATURE’S REMEDY: PLANT-BASED THERAPIES FOR DIABETIC ALZHEIMER’S
Main Article Content
Keywords
Diabetes, Alzheimer’s Disease, Type-3 diabetes, bioactive compounds, plant-based medicine, flavonoids, polyphenols, alkaloids
Abstract
Type 2 diabetes and Alzheimer's disease, when both conditions occur simultaneously, greatly worsen neurodegeneration and cognitive decline, making diabetic Alzheimer's disease a difficult healthcare issue to solve. Medicine derived from plants is gaining attention as a potential new treatment option due to its abundance of bioactive chemicals that have anti-diabetic and neuroprotective effects. This analysis focuses on the many ways in which chemicals found in plants have the potential to treat Alzheimer's disease in people with diabetes. Many chemicals found in plants have the potential to influence key pathways that are involved in the development of diabetes and Alzheimer's disease. Insulin signalling pathways, neuroinflammation, and amyloid-beta metabolism are all part of this category. Experts in the field may discover new ways to help diabetics slow down cognitive loss and neurodegeneration by using the wide variety of bioactive substances found in plants.
References
1. Jain S, Saraf S. Type 2 diabetes mellitus—Its global prevalence and therapeutic strategies. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2010 Jan 1;4(1):48-56.
2. Standl E, Khunti K, Hansen TB, et al. The global epidemics of diabetes in the 21st century: Current situation and perspectives. Eur J Prev Cardiol. 2019 Dec 1;26(2_suppl):7-14.
3. Halim M, Halim A. The effects of inflammation, aging and oxidative stress on the pathogenesis of diabetes mellitus (type 2 diabetes). Diabetes & metabolic syndrome: clinical research & reviews. 2019 Mar 1;13(2):1165-72.
4. Sheen YJ, Sheu WH. Association between hypoglycemia and dementia in patients with type 2 diabetes. Diabetes Res Clin Pract. 2016 Jun 1;116:279-87.
5. Tumminia A, Vinciguerra F, Parisi M, et al. Type 2 diabetes mellitus and Alzheimer’s disease: role of insulin signalling and therapeutic implications. Int J Mol Sci. 2018 Oct 24;19(11):3306.
6. Daulatzai MA. Quintessential risk factors: their role in promoting cognitive dysfunction and Alzheimer’s disease. Neurochem Res. 2012 Dec;37:2627-58.
7. Berlanga-Acosta J, Guillén-Nieto G, Rodríguez-Rodríguez N, et al. Insulin resistance at the crossroad of Alzheimer disease pathology: A review. Front Endocrinol. 2020 Nov 5;11:560375.
8. Barone E, Di Domenico F, Perluigi M, et al. The interplay among oxidative stress, brain insulin resistance and AMPK dysfunction contribute to neurodegeneration in type 2 diabetes and Alzheimer disease. Free Radic Biol Med. 2021 Nov 20;176:16-33.
9. Correia SC, Santos RX, Carvalho C, et al. Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer's disease and diabetes interrelation. Brain Res. 2012 Mar 2;1441:64-78.
10. de la Monte SM. The full spectrum of Alzheimer’s disease is rooted in metabolic derangements that drive type 3 diabetes. Adv Exp Med Biol. 2019:45-83.
11. Dyer AH, Vahdatpour C, Sanfeliu A, et al. The role of Insulin-Like Growth Factor 1 (IGF-1) in brain development, maturation and neuroplasticity. Neuroscience. 2016 Jun 14;325:89-99.
12. Lee S, Tong M, Hang S, et al. CSF and brain indices of insulin resistance, oxidative stress and neuro-inflammation in early versus late Alzheimer’s disease. J Alzheimers Dis Parkinsonism. 2013 Oct 31;3:128.
13. Kern W, Peters A, Fruehwald-Schultes B, et al. Improving influence of insulin on cognitive functions in humans. Neuroendocrinology. 2001 Oct 1;74(4):270-80.
14. de la Monte SM. Type 3 diabetes is sporadic Alzheimer׳ s disease: mini-review. Eur neuropsychopharmacol. 2014 Dec 1;24(12):1954-60.
15. Reger MA, Watson G, Green PS, et al. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-β in memory-impaired older adults. J Alzheimers Dis. 2008 Jan 1;13(3):323-31.
16. Chesik D, De Keyser J, Wilczak N. Insulin-like growth factor system regulates oligodendroglial cell behavior: therapeutic potential in CNS. J Mol Neurosci. 2008 May;35:81-90.
17. Bassil F, Fernagut PO, Bezard E, et al. Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: targets for disease modification?. Prog neurobiol. 2014 Jul 1;118:1-8.
18. De la Monte SM, Wands JR. Alzheimer's disease is type 3 diabetes—evidence reviewed. J Diabetes Sci Technol. 2008 Nov;2(6):1101-13.
19. Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer's disease a type 3 diabetes? A critical appraisal. Biochim Biophys Acta Mol Basis Dis. 2017 May 1;1863(5):1078-89.
20. Gupta A, Bisht B, Dey CS. Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like changes. Neuropharmacology. 2011 May 1;60(6):910-20.
21. Khan MA, Alam Q, Haque A, et al. Current progress on peroxisome proliferator-activated receptor gamma agonist as an emerging therapeutic approach for the treatment of Alzheimer's disease: an update. Curr Neuropharmacology. 2019 Mar 1;17(3):232-46.
22. McClean PL, Parthsarathy V, Faivre E, et al. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease. J Neurosci. 2011 Apr 27;31(17):6587-94.
23. Tramutola A, Arena A, Cini C, et al. Modulation of GLP-1 signaling as a novel therapeutic approach in the treatment of Alzheimer’s disease pathology. Expert Rev Neurother. 2017 Jan 2;17(1):59-75.
24. Patrick S, Corrigan R, Grizzanti J, et al. Neuroprotective effects of the amylin analog, pramlintide, on Alzheimer’s disease are associated with oxidative stress regulation mechanisms. J Alzheimers Dis. 2019 Jan 1;69(1):157-68.
25. Hoyer S. Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J pharmacol. 2004 Apr 19;490(1-3):115-25.
26. Li C, Liu W, Li X, et al. The novel GLP‐1/GIP analogue DA5‐CH reduces tau phosphorylation and normalizes theta rhythm in the icv. STZ rat model of AD. Brain and Behav. 2020 Mar;10(3):e01505.
27. Wang L, Zhang R, Hou X, et al. DA-JC1 improves learning and memory by antagonizing Aβ31–35-induced circadian rhythm disorder. Mol Brain. 2019 Dec;12:1-4.
28. Cao Y, Hölscher C, Hu MM, et al. DA5-CH, a novel GLP-1/GIP dual agonist, effectively ameliorates the cognitive impairments and pathology in the APP/PS1 mouse model of Alzheimer's disease. Eur J pharmacol. 2018 May 15;827:215-26.
29. Panagaki T, Gengler S, Hölscher C. The Novel DA–CH3 Dual Incretin Restores Endoplasmic Reticulum Stress and Autophagy Impairments to Attenuate Alzheimer-Like Pathology and Cognitive Decrements in the APP SWE/PS1 ΔE9 Mouse Model. J Alzheimers Dis. 2018 Jan 1;66(1):195-218.
30. De Felice FG, Vieira MN, Bomfim TR, et al. Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Aβ oligomers. Proc Natl Acad Sci. 2009 Feb 10;106(6):1971-6.
31. Lourenco MV, Clarke JR, Frozza RL, et al. TNF-α mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s β-amyloid oligomers in mice and monkeys. Cell Metab. 2013 Dec 3;18(6):831-43.
32. Craft S, Asthana S, Cook DG, et al. Insulin dose–response effects on memory and plasma amyloid precursor protein in Alzheimer’s disease: interactions with apolipoprotein E genotype. Psychoneuroendocrinology. 2003 Aug 1;28(6):809-22.
33. Reger MA, Watson G, Green PS, et al. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-β in memory-impaired older adults. J Alzheimers Dis. 2008a Jan 1;13(3):323-31.
34. Reger MA, Watson GS, Frey Ii WH, et al. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol aging. 2006 Mar 1;27(3):451-8.
35. Reger MA, Watson GS, Green PS, et al. Intranasal insulin improves cognition and modulates β-amyloid in early AD. Neurology. 2008b Feb 5;70(6):440-8.
36. Benedict C, Kern W, Schultes B, et al. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J Clin Endocrinol Metab. 2008 Apr 1;93(4):1339-44.
37. Batista AF, Forny‐Germano L, Clarke JR, et al. The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non‐human primate model of Alzheimer's disease. J Pathol. 2018 May;245(1):85-100.
38. McClean PL, Hölscher C. Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease. Neuropharmacology. 2014 Jan 1;76:57-67.
39. Bomfim TR, Forny-Germano L, Sathler LB, et al. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease–associated Aβ oligomers. J Clin Invest. 2012 Apr 2;122(4):1339-53.
40. Perry T, Haughey NJ, Mattson MP, et al. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J Pharmacol Exp Ther. 2002 Sep 1;302(3):881-8.
41. Escribano L, Simón AM, Gimeno E, et al. Rosiglitazone rescues memory impairment in Alzheimer's transgenic mice: mechanisms involving a reduced amyloid and tau pathology. Neuropsychopharmacology. 2010 Jun;35(7):1593-604.
42. Cai H, Cong WN, Ji S, et al. Metabolic dysfunction in Alzheimer's disease and related neurodegenerative disorders. Curr Alzheimer Res. 2012 Jan 1;9(1):5-17.
43. Sims-Robinson C, Kim B, Rosko A, et al. How does diabetes accelerate Alzheimer disease pathology?. Nat Rev Neurol. 2010 Oct;6(10):551-9.
44. González A, Calfío C, Churruca M, et al. Glucose metabolism and AD: Evidence for a potential diabetes type 3. Alzheimers Res Ther. 2022 Apr 20;14(1):56.
45. Zhou J, Chan L, Zhou S. Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease. Curr Med Chem. 2012 Jul 1;19(21):3523-31.
46. Xuan WT, Wang H, Zhou P, et al. Berberine ameliorates rats model of combined Alzheimer’s disease and type 2 diabetes mellitus via the suppression of endoplasmic reticulum stress. 3 Biotech. 2020 Aug;10:1-2.
47. Khan S, Khan HU, Khan FA, et al. Anti-Alzheimer and antioxidant effects of Nelumbo nucifera L. alkaloids, nuciferine and norcoclaurine in alloxan-Induced diabetic albino rats. Pharmaceuticals. 2022 Sep 28;15(10):1205.
48. Li JC, Shen XF, Shao JA, et al. The total alkaloids from Coptis chinensis Franch improve cognitive deficits in type 2 diabetic rats. Drug Des Devel Ther. 2018 Aug 31:2695-706.
49. Zengin G, Sarikürkçü C, Aktümsek A, et al. Antioxidant potential and inhibition of key enzymes linked to Alzheimer's diseases and diabetes mellitus by monoterpene-rich essential oil from Sideritis galatica Bornm. Endemic to Turkey. Records of Natural Products. 2016;10(2):195.
50. Conforti F, Statti GA, Tundis R, et al. In vitro activities of Citrus medica L. cv. Diamante (Diamante citron) relevant to treatment of diabetes and Alzheimer's disease. Phytother Res. 2007 May;21(5):427-33.
51. Liu YW, Zhu X, Lu Q, et al. Total saponins from Rhizoma Anemarrhenae ameliorate diabetes-associated cognitive decline in rats: involvement of amyloid-beta decrease in brain. J Ethnopharmacol. 2012 Jan 6;139(1):194-200.
52. Zhang YM, Zheng T, Huang TT, et al. Sarsasapogenin attenuates Alzheimer-like encephalopathy in diabetes. Phytomedicine. 2021 Oct 1;91:153686.
53. Lee HR, Kong SY, Sung SH, et al. DA-9801 and its saponins, dioscin and protodioscin, protect primary cortical neurons from hyperglycemia-induced neurotoxicity. J Funct Foods. 2019 Mar 1;54:231-40.
54. Feng H, Xue M, Deng H, et al. Ginsenoside and its therapeutic potential for cognitive impairment. Biomolecules. 2022 Sep 16;12(9):1310.
55. Khakpai F, Naseroleslami M, Moheb-Alian M, et al. Intra-gastrically administration of Stevia and particularly Nano-Stevia reversed the hyperglycemia, anxiety, and memory impairment in streptozotocin-induced diabetic rats. Physiol Behav. 2023 May 1;263:114100.
56. El-Marasy SA, Abdallah HM, El-Shenawy SM, et al. Anti-depressant effect of hesperidin in diabetic rats. Can J Physiol Pharmacol. 2014;92(11):945-52.
57. Li C, Zug C, Qu H, et al. Hesperidin ameliorates behavioral impairments and neuropathology of transgenic APP/PS1 mice. Behav Brain Res. 2015 Mar 15;281:32-42.
58. Liu X, Liu M, Mo Y, et al. Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats. Iran J Basic Med Sci. 2016 Apr;19(4):417-22. PMID: 27279986; PMCID: PMC4887715.
59. Wang D, Gao K, Li X, et al. Long-term naringin consumption reverses a glucose uptake defect and improves cognitive deficits in a mouse model of Alzheimer's disease. Pharmacol Biochem Behav. 2012 Jul 1;102(1):13-20.
60. Wang D, Yan J, Chen J, et al. Naringin improves neuronal insulin signaling, brain mitochondrial function, and cognitive function in high-fat diet-induced obese mice. Cell Mol Neurobiol. 2015 Oct;35:1061-71.
61. Yang W, Ma J, Liu Z, et al. Effect of naringenin on brain insulin signaling and cognitive functions in ICV-STZ induced dementia model of rats. Neurol Sci. 2014 May;35:741-51.
62. Rahigude A, Bhutada P, Kaulaskar S, et al. Participation of antioxidant and cholinergic system in protective effect of naringenin against type-2 diabetes-induced memory dysfunction in rats. Neuroscience. 2012 Dec 13;226:62-72.
63. Khan H, Ullah H, Aschner M, et al. Neuroprotective effects of quercetin in Alzheimer’s disease. Biomolecules. 2019 Dec 30;10(1):59.
64. Dhanya R. Quercetin for managing type 2 diabetes and its complications, an insight into multitarget therapy. Biomed Pharmacother. 2022 Feb 1;146:112560.
65. Bhutada P, Mundhada Y, Bansod K, et al. Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats. Neurobiol Learn Mem. 2010 Oct 1;94(3):293-302.
66. Sanna RS, Muthangi S, BK CS, et al. Grape seed proanthocyanidin extract and insulin prevents cognitive decline in type 1 diabetic rat by impacting Bcl-2 and Bax in the prefrontal cortex. Metab Brain Dis. 2019 Feb;34:103-17.
67. Lu M, Xu L, Li B, et al. Protective effects of grape seed proanthocyanidin extracts on cerebral cortex of streptozotocin-induced diabetic rats through modulating AGEs/RAGE/NF-κB pathway. J Nutr Sci Vitaminol. 2010;56(2):87-97.
68. Alfaris NA, Alshammari GM, Altamimi JZ, et al. Ellagic acid prevents streptozotocin-induced hippocampal damage and memory loss in rats by stimulating Nrf2 and nuclear factor-κB, and activating insulin receptor substrate/PI3K/Akt axis. J Physiol Pharmacol. 2021 Aug 1;72(4).
69. Kumar M, Bansal N. Ellagic acid prevents dementia through modulation of PI3-kinase-endothelial nitric oxide synthase signalling in streptozotocin-treated rats. Naunyn Schmiedebergs Arch Pharmacol. 2018 Sep;391(9):987-1001.
70. Lim KG, Varatharajan R, Muthuraman A. The attenuating effect of Beta-carotene on Streptozotocin Induced Diabetic Vascular dementia symptoms in rats. Molecules. 2022 Jul 4;27(13):4293.
71. Fatani AJ, Parmar MY, Abuohashish HM, et al. Protective effect of lutein supplementation on oxidative stress and inflammatory progression in cerebral cortex of streptozotocin-induced diabetes in rats. Neurochemical Journal. 2016 Jan;10:69-76.
72. Zhou X, Wang S, Ding X, et al. Zeaxanthin improves diabetes-induced cognitive deficit in rats through activiting PI3K/AKT signaling pathway. Brain Res Bull. 2017 Jun 1;132:190-8.
73. Lopresti AL, Smith SJ, Drummond PD. The Effects of lutein and zeaxanthin supplementation on cognitive function in adults with self-reported mild cognitive complaints: A randomized, double-blind, placebo-controlled study. Front Nutr. 2022 Feb 17;9:843512.
74. Huang J, Huang N, Mao Q, et al. Natural bioactive compounds in Alzheimer's disease: From the perspective of type 3 diabetes mellitus. Front Aging Neurosci. 2023 Mar 16;15:1130253.
75. Tian X, Liu Y, Ren G, et al. Resveratrol limits diabetes-associated cognitive decline in rats by preventing oxidative stress and inflammation and modulating hippocampal structural synaptic plasticity. Brain Res. 2016 Nov 1;1650:1-9.
76. Wang X, Fang H, Xu G, et al. Resveratrol prevents cognitive impairment in type 2 diabetic mice by upregulating Nrf2 expression and transcriptional level. Diabetes Metab Syndr Obes. 2020 Apr 7:1061-75.
77. Mi Y, Qi G, Fan R, et al. EGCG ameliorates high‐fat–and high‐fructose‐induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS. FASEB J. 2017 Nov;31(11):4998-5011.
78. Kou J, Lv C, Cheng L, et al. Tea polyphenol ameliorates memory impairment in aged type 2 diabetic rats by modulating hippocampal glucose uptake/metabolism and O-GlcNAc glycosylation/phosphorylation of Tau. J Funct Foods. 2024 Jun 1;117:106242.
79. Sharifzadeh M, Ranjbar A, Hosseini A, et al. The effect of green tea extract on oxidative stress and spatial learning in streptozotocin-diabetic rats. Iran J Pharm Res. 2017;16(1):201.
80. Baluchnejadmojarad T, Roghani M. Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress. Behav Brain Res. 2011 Oct 31;224(2):305-10.
81. Reddy PH, Manczak M, Yin X, et al. Protective effects of Indian spice curcumin against amyloid-β in Alzheimer’s disease. J Alzheimers Dis. 2018 Jan 1;61(3):843-66.
82. Weisberg SP, Leibel R, Tortoriello DV. Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinology. 2008 Jul 1;149(7):3549-58.
83. Miao C, Chen H, Li Y, et al. Curcumin and its analog alleviate diabetes-induced damages by regulating inflammation and oxidative stress in brain of diabetic rats. Diabetol Metab Syndr. 2021 Dec;13:1-1.
84. Zheng Y, Zhang J, Zhao Y, et al. Curcumin protects against cognitive impairments in a rat model of chronic cerebral hypoperfusion combined with diabetes mellitus by suppressing neuroinflammation, apoptosis, and pyroptosis. Int Immunopharmacol. 2021 Apr 1;93:107422.
2. Standl E, Khunti K, Hansen TB, et al. The global epidemics of diabetes in the 21st century: Current situation and perspectives. Eur J Prev Cardiol. 2019 Dec 1;26(2_suppl):7-14.
3. Halim M, Halim A. The effects of inflammation, aging and oxidative stress on the pathogenesis of diabetes mellitus (type 2 diabetes). Diabetes & metabolic syndrome: clinical research & reviews. 2019 Mar 1;13(2):1165-72.
4. Sheen YJ, Sheu WH. Association between hypoglycemia and dementia in patients with type 2 diabetes. Diabetes Res Clin Pract. 2016 Jun 1;116:279-87.
5. Tumminia A, Vinciguerra F, Parisi M, et al. Type 2 diabetes mellitus and Alzheimer’s disease: role of insulin signalling and therapeutic implications. Int J Mol Sci. 2018 Oct 24;19(11):3306.
6. Daulatzai MA. Quintessential risk factors: their role in promoting cognitive dysfunction and Alzheimer’s disease. Neurochem Res. 2012 Dec;37:2627-58.
7. Berlanga-Acosta J, Guillén-Nieto G, Rodríguez-Rodríguez N, et al. Insulin resistance at the crossroad of Alzheimer disease pathology: A review. Front Endocrinol. 2020 Nov 5;11:560375.
8. Barone E, Di Domenico F, Perluigi M, et al. The interplay among oxidative stress, brain insulin resistance and AMPK dysfunction contribute to neurodegeneration in type 2 diabetes and Alzheimer disease. Free Radic Biol Med. 2021 Nov 20;176:16-33.
9. Correia SC, Santos RX, Carvalho C, et al. Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer's disease and diabetes interrelation. Brain Res. 2012 Mar 2;1441:64-78.
10. de la Monte SM. The full spectrum of Alzheimer’s disease is rooted in metabolic derangements that drive type 3 diabetes. Adv Exp Med Biol. 2019:45-83.
11. Dyer AH, Vahdatpour C, Sanfeliu A, et al. The role of Insulin-Like Growth Factor 1 (IGF-1) in brain development, maturation and neuroplasticity. Neuroscience. 2016 Jun 14;325:89-99.
12. Lee S, Tong M, Hang S, et al. CSF and brain indices of insulin resistance, oxidative stress and neuro-inflammation in early versus late Alzheimer’s disease. J Alzheimers Dis Parkinsonism. 2013 Oct 31;3:128.
13. Kern W, Peters A, Fruehwald-Schultes B, et al. Improving influence of insulin on cognitive functions in humans. Neuroendocrinology. 2001 Oct 1;74(4):270-80.
14. de la Monte SM. Type 3 diabetes is sporadic Alzheimer׳ s disease: mini-review. Eur neuropsychopharmacol. 2014 Dec 1;24(12):1954-60.
15. Reger MA, Watson G, Green PS, et al. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-β in memory-impaired older adults. J Alzheimers Dis. 2008 Jan 1;13(3):323-31.
16. Chesik D, De Keyser J, Wilczak N. Insulin-like growth factor system regulates oligodendroglial cell behavior: therapeutic potential in CNS. J Mol Neurosci. 2008 May;35:81-90.
17. Bassil F, Fernagut PO, Bezard E, et al. Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: targets for disease modification?. Prog neurobiol. 2014 Jul 1;118:1-8.
18. De la Monte SM, Wands JR. Alzheimer's disease is type 3 diabetes—evidence reviewed. J Diabetes Sci Technol. 2008 Nov;2(6):1101-13.
19. Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer's disease a type 3 diabetes? A critical appraisal. Biochim Biophys Acta Mol Basis Dis. 2017 May 1;1863(5):1078-89.
20. Gupta A, Bisht B, Dey CS. Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like changes. Neuropharmacology. 2011 May 1;60(6):910-20.
21. Khan MA, Alam Q, Haque A, et al. Current progress on peroxisome proliferator-activated receptor gamma agonist as an emerging therapeutic approach for the treatment of Alzheimer's disease: an update. Curr Neuropharmacology. 2019 Mar 1;17(3):232-46.
22. McClean PL, Parthsarathy V, Faivre E, et al. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease. J Neurosci. 2011 Apr 27;31(17):6587-94.
23. Tramutola A, Arena A, Cini C, et al. Modulation of GLP-1 signaling as a novel therapeutic approach in the treatment of Alzheimer’s disease pathology. Expert Rev Neurother. 2017 Jan 2;17(1):59-75.
24. Patrick S, Corrigan R, Grizzanti J, et al. Neuroprotective effects of the amylin analog, pramlintide, on Alzheimer’s disease are associated with oxidative stress regulation mechanisms. J Alzheimers Dis. 2019 Jan 1;69(1):157-68.
25. Hoyer S. Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J pharmacol. 2004 Apr 19;490(1-3):115-25.
26. Li C, Liu W, Li X, et al. The novel GLP‐1/GIP analogue DA5‐CH reduces tau phosphorylation and normalizes theta rhythm in the icv. STZ rat model of AD. Brain and Behav. 2020 Mar;10(3):e01505.
27. Wang L, Zhang R, Hou X, et al. DA-JC1 improves learning and memory by antagonizing Aβ31–35-induced circadian rhythm disorder. Mol Brain. 2019 Dec;12:1-4.
28. Cao Y, Hölscher C, Hu MM, et al. DA5-CH, a novel GLP-1/GIP dual agonist, effectively ameliorates the cognitive impairments and pathology in the APP/PS1 mouse model of Alzheimer's disease. Eur J pharmacol. 2018 May 15;827:215-26.
29. Panagaki T, Gengler S, Hölscher C. The Novel DA–CH3 Dual Incretin Restores Endoplasmic Reticulum Stress and Autophagy Impairments to Attenuate Alzheimer-Like Pathology and Cognitive Decrements in the APP SWE/PS1 ΔE9 Mouse Model. J Alzheimers Dis. 2018 Jan 1;66(1):195-218.
30. De Felice FG, Vieira MN, Bomfim TR, et al. Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Aβ oligomers. Proc Natl Acad Sci. 2009 Feb 10;106(6):1971-6.
31. Lourenco MV, Clarke JR, Frozza RL, et al. TNF-α mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s β-amyloid oligomers in mice and monkeys. Cell Metab. 2013 Dec 3;18(6):831-43.
32. Craft S, Asthana S, Cook DG, et al. Insulin dose–response effects on memory and plasma amyloid precursor protein in Alzheimer’s disease: interactions with apolipoprotein E genotype. Psychoneuroendocrinology. 2003 Aug 1;28(6):809-22.
33. Reger MA, Watson G, Green PS, et al. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-β in memory-impaired older adults. J Alzheimers Dis. 2008a Jan 1;13(3):323-31.
34. Reger MA, Watson GS, Frey Ii WH, et al. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol aging. 2006 Mar 1;27(3):451-8.
35. Reger MA, Watson GS, Green PS, et al. Intranasal insulin improves cognition and modulates β-amyloid in early AD. Neurology. 2008b Feb 5;70(6):440-8.
36. Benedict C, Kern W, Schultes B, et al. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J Clin Endocrinol Metab. 2008 Apr 1;93(4):1339-44.
37. Batista AF, Forny‐Germano L, Clarke JR, et al. The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non‐human primate model of Alzheimer's disease. J Pathol. 2018 May;245(1):85-100.
38. McClean PL, Hölscher C. Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease. Neuropharmacology. 2014 Jan 1;76:57-67.
39. Bomfim TR, Forny-Germano L, Sathler LB, et al. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease–associated Aβ oligomers. J Clin Invest. 2012 Apr 2;122(4):1339-53.
40. Perry T, Haughey NJ, Mattson MP, et al. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J Pharmacol Exp Ther. 2002 Sep 1;302(3):881-8.
41. Escribano L, Simón AM, Gimeno E, et al. Rosiglitazone rescues memory impairment in Alzheimer's transgenic mice: mechanisms involving a reduced amyloid and tau pathology. Neuropsychopharmacology. 2010 Jun;35(7):1593-604.
42. Cai H, Cong WN, Ji S, et al. Metabolic dysfunction in Alzheimer's disease and related neurodegenerative disorders. Curr Alzheimer Res. 2012 Jan 1;9(1):5-17.
43. Sims-Robinson C, Kim B, Rosko A, et al. How does diabetes accelerate Alzheimer disease pathology?. Nat Rev Neurol. 2010 Oct;6(10):551-9.
44. González A, Calfío C, Churruca M, et al. Glucose metabolism and AD: Evidence for a potential diabetes type 3. Alzheimers Res Ther. 2022 Apr 20;14(1):56.
45. Zhou J, Chan L, Zhou S. Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease. Curr Med Chem. 2012 Jul 1;19(21):3523-31.
46. Xuan WT, Wang H, Zhou P, et al. Berberine ameliorates rats model of combined Alzheimer’s disease and type 2 diabetes mellitus via the suppression of endoplasmic reticulum stress. 3 Biotech. 2020 Aug;10:1-2.
47. Khan S, Khan HU, Khan FA, et al. Anti-Alzheimer and antioxidant effects of Nelumbo nucifera L. alkaloids, nuciferine and norcoclaurine in alloxan-Induced diabetic albino rats. Pharmaceuticals. 2022 Sep 28;15(10):1205.
48. Li JC, Shen XF, Shao JA, et al. The total alkaloids from Coptis chinensis Franch improve cognitive deficits in type 2 diabetic rats. Drug Des Devel Ther. 2018 Aug 31:2695-706.
49. Zengin G, Sarikürkçü C, Aktümsek A, et al. Antioxidant potential and inhibition of key enzymes linked to Alzheimer's diseases and diabetes mellitus by monoterpene-rich essential oil from Sideritis galatica Bornm. Endemic to Turkey. Records of Natural Products. 2016;10(2):195.
50. Conforti F, Statti GA, Tundis R, et al. In vitro activities of Citrus medica L. cv. Diamante (Diamante citron) relevant to treatment of diabetes and Alzheimer's disease. Phytother Res. 2007 May;21(5):427-33.
51. Liu YW, Zhu X, Lu Q, et al. Total saponins from Rhizoma Anemarrhenae ameliorate diabetes-associated cognitive decline in rats: involvement of amyloid-beta decrease in brain. J Ethnopharmacol. 2012 Jan 6;139(1):194-200.
52. Zhang YM, Zheng T, Huang TT, et al. Sarsasapogenin attenuates Alzheimer-like encephalopathy in diabetes. Phytomedicine. 2021 Oct 1;91:153686.
53. Lee HR, Kong SY, Sung SH, et al. DA-9801 and its saponins, dioscin and protodioscin, protect primary cortical neurons from hyperglycemia-induced neurotoxicity. J Funct Foods. 2019 Mar 1;54:231-40.
54. Feng H, Xue M, Deng H, et al. Ginsenoside and its therapeutic potential for cognitive impairment. Biomolecules. 2022 Sep 16;12(9):1310.
55. Khakpai F, Naseroleslami M, Moheb-Alian M, et al. Intra-gastrically administration of Stevia and particularly Nano-Stevia reversed the hyperglycemia, anxiety, and memory impairment in streptozotocin-induced diabetic rats. Physiol Behav. 2023 May 1;263:114100.
56. El-Marasy SA, Abdallah HM, El-Shenawy SM, et al. Anti-depressant effect of hesperidin in diabetic rats. Can J Physiol Pharmacol. 2014;92(11):945-52.
57. Li C, Zug C, Qu H, et al. Hesperidin ameliorates behavioral impairments and neuropathology of transgenic APP/PS1 mice. Behav Brain Res. 2015 Mar 15;281:32-42.
58. Liu X, Liu M, Mo Y, et al. Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats. Iran J Basic Med Sci. 2016 Apr;19(4):417-22. PMID: 27279986; PMCID: PMC4887715.
59. Wang D, Gao K, Li X, et al. Long-term naringin consumption reverses a glucose uptake defect and improves cognitive deficits in a mouse model of Alzheimer's disease. Pharmacol Biochem Behav. 2012 Jul 1;102(1):13-20.
60. Wang D, Yan J, Chen J, et al. Naringin improves neuronal insulin signaling, brain mitochondrial function, and cognitive function in high-fat diet-induced obese mice. Cell Mol Neurobiol. 2015 Oct;35:1061-71.
61. Yang W, Ma J, Liu Z, et al. Effect of naringenin on brain insulin signaling and cognitive functions in ICV-STZ induced dementia model of rats. Neurol Sci. 2014 May;35:741-51.
62. Rahigude A, Bhutada P, Kaulaskar S, et al. Participation of antioxidant and cholinergic system in protective effect of naringenin against type-2 diabetes-induced memory dysfunction in rats. Neuroscience. 2012 Dec 13;226:62-72.
63. Khan H, Ullah H, Aschner M, et al. Neuroprotective effects of quercetin in Alzheimer’s disease. Biomolecules. 2019 Dec 30;10(1):59.
64. Dhanya R. Quercetin for managing type 2 diabetes and its complications, an insight into multitarget therapy. Biomed Pharmacother. 2022 Feb 1;146:112560.
65. Bhutada P, Mundhada Y, Bansod K, et al. Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats. Neurobiol Learn Mem. 2010 Oct 1;94(3):293-302.
66. Sanna RS, Muthangi S, BK CS, et al. Grape seed proanthocyanidin extract and insulin prevents cognitive decline in type 1 diabetic rat by impacting Bcl-2 and Bax in the prefrontal cortex. Metab Brain Dis. 2019 Feb;34:103-17.
67. Lu M, Xu L, Li B, et al. Protective effects of grape seed proanthocyanidin extracts on cerebral cortex of streptozotocin-induced diabetic rats through modulating AGEs/RAGE/NF-κB pathway. J Nutr Sci Vitaminol. 2010;56(2):87-97.
68. Alfaris NA, Alshammari GM, Altamimi JZ, et al. Ellagic acid prevents streptozotocin-induced hippocampal damage and memory loss in rats by stimulating Nrf2 and nuclear factor-κB, and activating insulin receptor substrate/PI3K/Akt axis. J Physiol Pharmacol. 2021 Aug 1;72(4).
69. Kumar M, Bansal N. Ellagic acid prevents dementia through modulation of PI3-kinase-endothelial nitric oxide synthase signalling in streptozotocin-treated rats. Naunyn Schmiedebergs Arch Pharmacol. 2018 Sep;391(9):987-1001.
70. Lim KG, Varatharajan R, Muthuraman A. The attenuating effect of Beta-carotene on Streptozotocin Induced Diabetic Vascular dementia symptoms in rats. Molecules. 2022 Jul 4;27(13):4293.
71. Fatani AJ, Parmar MY, Abuohashish HM, et al. Protective effect of lutein supplementation on oxidative stress and inflammatory progression in cerebral cortex of streptozotocin-induced diabetes in rats. Neurochemical Journal. 2016 Jan;10:69-76.
72. Zhou X, Wang S, Ding X, et al. Zeaxanthin improves diabetes-induced cognitive deficit in rats through activiting PI3K/AKT signaling pathway. Brain Res Bull. 2017 Jun 1;132:190-8.
73. Lopresti AL, Smith SJ, Drummond PD. The Effects of lutein and zeaxanthin supplementation on cognitive function in adults with self-reported mild cognitive complaints: A randomized, double-blind, placebo-controlled study. Front Nutr. 2022 Feb 17;9:843512.
74. Huang J, Huang N, Mao Q, et al. Natural bioactive compounds in Alzheimer's disease: From the perspective of type 3 diabetes mellitus. Front Aging Neurosci. 2023 Mar 16;15:1130253.
75. Tian X, Liu Y, Ren G, et al. Resveratrol limits diabetes-associated cognitive decline in rats by preventing oxidative stress and inflammation and modulating hippocampal structural synaptic plasticity. Brain Res. 2016 Nov 1;1650:1-9.
76. Wang X, Fang H, Xu G, et al. Resveratrol prevents cognitive impairment in type 2 diabetic mice by upregulating Nrf2 expression and transcriptional level. Diabetes Metab Syndr Obes. 2020 Apr 7:1061-75.
77. Mi Y, Qi G, Fan R, et al. EGCG ameliorates high‐fat–and high‐fructose‐induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS. FASEB J. 2017 Nov;31(11):4998-5011.
78. Kou J, Lv C, Cheng L, et al. Tea polyphenol ameliorates memory impairment in aged type 2 diabetic rats by modulating hippocampal glucose uptake/metabolism and O-GlcNAc glycosylation/phosphorylation of Tau. J Funct Foods. 2024 Jun 1;117:106242.
79. Sharifzadeh M, Ranjbar A, Hosseini A, et al. The effect of green tea extract on oxidative stress and spatial learning in streptozotocin-diabetic rats. Iran J Pharm Res. 2017;16(1):201.
80. Baluchnejadmojarad T, Roghani M. Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress. Behav Brain Res. 2011 Oct 31;224(2):305-10.
81. Reddy PH, Manczak M, Yin X, et al. Protective effects of Indian spice curcumin against amyloid-β in Alzheimer’s disease. J Alzheimers Dis. 2018 Jan 1;61(3):843-66.
82. Weisberg SP, Leibel R, Tortoriello DV. Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinology. 2008 Jul 1;149(7):3549-58.
83. Miao C, Chen H, Li Y, et al. Curcumin and its analog alleviate diabetes-induced damages by regulating inflammation and oxidative stress in brain of diabetic rats. Diabetol Metab Syndr. 2021 Dec;13:1-1.
84. Zheng Y, Zhang J, Zhao Y, et al. Curcumin protects against cognitive impairments in a rat model of chronic cerebral hypoperfusion combined with diabetes mellitus by suppressing neuroinflammation, apoptosis, and pyroptosis. Int Immunopharmacol. 2021 Apr 1;93:107422.
Article Sidebar
Published
Feb 24, 2022
Article Details
How to Cite
Sayyada Saleha Momina, & Kumaraswamy Gandla. (2022). NATURE’S REMEDY: PLANT-BASED THERAPIES FOR DIABETIC ALZHEIMER’S. Journal of Population Therapeutics and Clinical Pharmacology, 29(02), 399-411. https://doi.org/10.53555/jptcp.v29i02.6486
Section
Articles
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Author Biographies
Sayyada Saleha Momina
Department of Pharmacognosy and Phytochemistry, Research scholar, Chaitanya (Deemed to be University), Kishanpura, Hanamkonda, Warangal Urban District – 506001, Telangana, India.
Kumaraswamy Gandla
Professor and Head, Department of Pharmaceutical Analysis, Kishanpura, Hanamkonda, Warangal Urban District – 506001, Telangana, India.
How to Cite
Sayyada Saleha Momina, & Kumaraswamy Gandla. (2022). NATURE’S REMEDY: PLANT-BASED THERAPIES FOR DIABETIC ALZHEIMER’S. Journal of Population Therapeutics and Clinical Pharmacology, 29(02), 399-411. https://doi.org/10.53555/jptcp.v29i02.6486