Dietary supplements for prevention of Alzheimer’s disease: In vivo and in silico molecular docking studies | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 4، دوره 28، شماره 2، اردیبهشت 2025، صفحه 170-180 اصل مقاله (488.08 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2024.79960.17320 | ||
| نویسندگان | ||
| Doha Abdo Mohamed؛ Rasha Salah Mohamed؛ Karem Fouda؛ Hoda Bakr Mabrok* | ||
| Nutrition and Food Science Department, Food Industries and Nutrition Institute, National Research Centre, Dokki 12622, Cairo, Egypt | ||
| چکیده | ||
| Objective(s): Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases in people over 65. The present research aimed to investigate the potential of different dietary supplements (DS) in preventing AD in an experimental animal model and in silico study. Materials and Methods: Three DS containing a mixture of wheat-germ oil and black pepper extract/or turmeric extract were prepared. Total phenolic content, HPLC-phenolic profile, phytosterols content, fatty-acids profile, and anti-oxidant activity were evaluated in all DS. The protective effect of the prepared DS was assessed through their impact on cholinergic neurotransmission and the gene expression of GSK3β, APP, and Akt. Oxidative stress and inflammatory markers were evaluated. The inhibition activities against acetylcholinesterase (AChE) and reduction of amyloid-β aggregation of the major phytochemicals present in the studied DS were evaluated using in silico molecular docking study. Results: Molecular docking revealed that rosmarinic acid and β-Sitosterol exhibited the strongest binding affinities for AChE and Amyloid-β, respectively. The results showed that all DS reduced cholinergic neurotransmission, decreased TNF-α as an inflammatory marker, and improved oxidative stress status. All DS down-regulated the expression of GSK3β and APP while significantly up-regulating the expression of the Akt gene. Conclusion: The present study concluded that all DS enhanced cholinergic neurotransmission, reduced inflammation, and improved oxidative stress status by impacting the expression of GSK3β, Akt, and APP genes. Rosmarinic acid and β-sitosterol showed promising effects for treating AD, according to an in silico molecular docking study. The studied dietary supplements were considered promising candidates for the prevention of AD. | ||
| کلیدواژهها | ||
| Acetylcholinesterase Alzheimer’s disease؛ Amyloid-β؛ Dietary supplements؛ Gene expression؛ Molecular docking | ||
| مراجع | ||
|
1. Moreta MP, Burgos-Alonso N, Torrecilla M, Marco-Contelles J, Bruzos-Cidón C. Efficacy of acetylcholinesterase inhibitors on cognitive function in alzheimer’s disease. Review of reviews. Biomedicines 2021; 9: 1689-1702. 2. Rostagno AA. Pathogenesis of Alzheimer’s disease. Int J Mol Sci 2023; 24: 107-110. 3. Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2016 (GBD 2016) Incidence, Prevalence, and Years Lived with Disability 1990–2016; Institute for Health Metrics and Evaluation (IHME): Seattle, DC, USA. 2017. 4. Ma C, Hong F, Yang S. Amyloidosis in alzheimer’s disease: Pathogeny, etiology, and related therapeutic directions. Molecules 2022; 27: 1210-1221. 5. Sanajou S, Erkekoğlu P, Şahin G, Baydar T. Role of aluminum exposure on Alzheimer’s disease and related glycogen synthase kinase pathway. Drug Chem Toxicol 2023; 46: 510-522. 6. Chen ZR, Huang JB, Yang SL, Hong FF. Role of cholinergic signaling in alzheimer’s disease. Molecules 2022; 27: 1816-1838. 7. Breijyeh Z, Karaman R. Comprehensive review on Alzheimer’s disease: Causes and treatment. Molecules 2020; 25: 5789-5816. 8. Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement 2018;14: 535-562. 9. Westermark P, Benson MD, Buxbaum JN, Cohen AS, Frangione B, Ikeda SI, et al. A primer of amyloid nomenclature. Amyloid 2007;14: 179-183. 10. Chen GF, Xu TH, Yan Y, Zhou YR, Jiang Y, Melcher K, et al. Amyloid beta: Structure, biology and structure-based therapeutic development. Acta Pharmacol Sin 2017; 38: 1205-1235. 11. Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer’s disease: Targeting the cholinergic system. Curr Neuropharmacol 2016; 14: 101-115. 12. Semwal BC, Garabadu D. Amyloid β (1-42) downregulates adenosine-2b receptors in addition to mitochondrial impairment and cholinergic dysfunction in memory-sensitive mouse brain regions. J Recept Signal Transduct Res 2020; 40: 531-540. 13. Zueva IV, Vasilieva EA, Gaynanova GA, Moiseenko AV, Burtseva AD, Boyko KM, et al. Can activation of acetylcholinesterase by β-amyloid peptide decrease the effectiveness of cholinesterase inhibitors? Int J Mol Sci 2023; 24: 16395-16410. 14. Rees TM, Brimijoin S. The role of acetylcholinesterase in the pathogenesis of Alzheimer’s disease. Drugs Today (Barc) 2003; 39: 75-83. 15. Cai Z, Zhao Y, Zhao B. Roles of glycogen synthase kinase 3 in Alzheimer’s disease. Curr Alzheimer Res 2012; 9: 864-879. 16. Lauretti E, Dincer O, Praticò D. Glycogen synthase kinase-3 signaling in Alzheimer’s disease. Biochim Biophys Acta Mol Cell Res 2020; 1867: 118664-118680. 17. Al-Khayri JM, Sahana GR, Nagella P, Joseph BV, Alessa FM, Al-Mssallem MQ. Flavonoids as potential anti-inflammatory molecules: A review. Molecules 2022; 27: 2901-2924. 18. Gregory J, Vengalasetti YV, Bredesen DE, Rao RV. Neuroprotective herbs for the management of Alzheimer’s disease. Biomolecules 2021; 11: 543-561. 19. AbdEl-Hack ME, El-Saadony MT, Swelum AA, Arif M, Ghanima MMA, Shukry M, et al. Curcumin, the active substance of turmeric: Its effects on health and ways to improve its bioavailability. J Sci Food Agric 2021;101: 5747-5762. 20. Andrew R, Izzo AA. Principles of pharmacological research of nutraceuticals. Br J Pharmacol 2017; 174: 1177–1194. 21. Soleimani V, Sahebkar A, Hosseinzadeh H. Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances: Review. Phytother Res 2018; 32: 985-995. 22. Zhang L, Fiala M, Cashman J, Sayre J, Espinosa A, Mahanian M, et al. Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer’s disease patients. J Alzheimers Dis 2006; 10: 1-7. 23. Fernández-Lázaro D, Mielgo-Ayuso J, Martínez AC, Seco-Calvo J. Iron and physical activity: Bioavailability enhancers, properties of black pepper (bioperine®) and potential applications. Nutrients 2020; 12: 1886-1897. 24. Heidari-Beni M, Moravejolahkami AR, Gorgian P, Askari Gh, Tarrahi MJ, Esfahani N. Herbal formulation “turmeric extract, black pepper, and ginger” versus Naproxen for chronic knee osteoarthritis: A randomized, double-blind, controlled clinical trial. Phytother Res 2020; 34: 2067-2073. 25. Luo, H, Li Zh, Straight CR, Wang Q, Zhou J, Sun Y, et al. Black pepper and vegetable oil-based emulsion synergistically enhance carotenoid bioavailability of raw vegetables in humans. Food Chem 2022; 373: 131277. 26. Swiderski J, Sakkal S, Apostolopoulos V, Zulli A, Gadanec LK. Combination of taurine and black pepper extract as a treatment for cardiovascular and coronary artery diseases. Nutrients 2023; 15: 2562-2591. 27. Wang, C, Cai Zh, Wang W, Wei M, Kou D, Li T, et al. Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer’s disease. J Nutr Biochem 2019; 70: 147-155. 28. Feltre G, Sartori T, Silva KFC, Dacanal GC, Menegalli FC, Hubinger MD. Encapsulation of wheat germ oil in alginate-gelatinized corn starch beads: Physicochemical properties and tocopherols’ stability. J Food Sci 2020; 85: 2124-2133. 29. Harrabi S, Ferchichi A, Fellah H, Feki M, Hosseinian F. Chemical composition and in vitro anti-inflammatory activity of wheat germ oil depending on the extraction procedure. J Oleo Sci 2021; 70: 1051-1058. 30. Mohamed DA, Mohammed SE, Hamed IM. Chia seeds oil enriched with phytosterols and mucilage as a cardioprotective dietary supplement towards inflammation, oxidative stress, and dyslipidemia. J Herbmed Pharmacol 2022; 11: 83-90. 31. Ghafoor, K, Özcan MM, AL-Juhaımı F, Babıker EE, Sarker ZI, Ahmed IAM, et al. Nutritional composition, extraction and utilization of wheat germ oil: A review. Eur. J Lipid Sci Technol 2017; 119: 1600160. 32. Mohamed DA, Mohammed SE, El-Sayed, HS, Mabrok H, Mohamed RS. Ameliorative effect of probiotic-fermented milk and costus extract in Alzheimer’s disease model induced by D-galactose and aluminum chloride. Egypt J Chem 2022; 65:411-421. 33. Mohamed DA, Ismael AI, Ibrahim AR. Studying the anti-inflammatory and biochemical effects of wheat germ oil. Deutsche Lebensmittel-Rundschau 2005; 101: 66-72. 34. Singleton VL, Orthofer R, Lamuela-Ravento´s RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Method Enzymol 1999; 299: 152-178. 35. Shekhar TC, Anju G. Antioxidant activity by DPPH radical scavenging method of Ageratum conyzoides Linn. leaves. Am J Ethnomed 2014; 1: 244-249. 36. AOAC. Official Methods of Analysis of the Association of Official Analytical Chemists, 19th ed., Washington D.C., USA, 2012. 37. Mohamed DA, Hamed IM, Mohammed SE. Utilization of grape and apricot fruits by-products as cheap source for biologically active compounds for health promotion. Egypt J Chem 2021; 64: 2037-2045. 38. National Center for Biotechnology Information. PubChem. https://pubchem.ncbi.nlm.nih.gov/ 2023. 39. Hanwell, MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. J Cheminformatics 2012; 4: 17-33. 40. The UniProt Consortium. UniProt: A worldwide hub of protein knowledge. Nucl Acids Res 2019; 47: D506-D515. 41. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 2009; 30: 2785-2791. 42. Trott O, Olson AJ. AutoDock vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31: 455-461. 43. BIOVIA, Dassault Systèmes, BIOVIA Workbook, Release 2020; BIOVIA Pipeline Pilot, Release 2020, San Diego: Dassault Systèmes, 2020. 44. Bilgic, Y, Demir EA, Bilgic N, Dogan H, Tutuk O, Tumer C, et al. Detrimental effects of chia (Salvia hispanica L.) seeds on learning and memory in aluminum chlorideinduced experimental Alzheimer’s disease. Acta Neurobiol Exp (Wars) 2018; 78: 322-331. 45. Vaisi-Raygani, A, Rahimi Z, Kharazi H, Tavilani H, Aminiani M, Kiani A, et al. Determination of butyrylcholinesterase (BChE) phenotypes to predict the risk of prolonged apnea in persons receiving succinylcholine in the healthy population of western. Iran Clin Biochem 2007; 40: 629-633. 46. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-126. 47. Satoh K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 1978; 90: 37-43. 48. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCt method. Methods 2001; 25: 402-408. 49. Yang, S, Chen Zh, Cao M, Li R, Wang Zh, Zhang M. Pioglitazone ameliorates Aβ42 deposition in rats with diet-induced insulin resistance associated with AKT/GSK3β activation. Mol Med Rep 2017; 15: 2588-2594. 50. Li, H, Kang T, Qi B, Kong L, Jiao Y, Cao Y, et al. Neuroprotective effects of ginseng protein on PI3K/Akt signaling pathway in the hippocampus of Dgalactose/ AlCl3 inducing rats model of Alzheimer’s disease. J Ethnopharmacol 2016; 179: 162-169. 51. Khan HA, Abdelhalim MK, Alhomida AS, Al Ayed MS. Transient increase in IL-1β, IL-6 and TNF-α gene expression in rat liver exposed to gold nanoparticles. Genet Mol Res 2013; 12: 5851-5857. 52. Olawuyi TS, Akinola KB, Adelakun SA, Ogunlade BS, Akingbade GT. Effects of aqueous leaf extract of lawsonia inermis on aluminum-induced oxidative stress and adult wistar rat. pituitary gland histology. JBRA Assist Reprod 2019; 23:117-122. 53. Mocanu CS, Jureschi M, Drochioiu G. Aluminium binding to modified amyloid-peptides: implications for Alzheimer’s disease. Molecules 2020; 25: 4536- 4562. 54. Mold MJ, O’Farrell A, Morris B, Exley C. Aluminum and neurofibrillary tangle co-localization in familial alzheimer’s disease and related neurological disorders. J Alzheimers Dis 2020; 78: 139-149. 55. Al-Okbi SY, Mohamed DA, Abdel Fatah M, Abdel Aal K, Mohammed SE. Evaluation of plant food extracts in experimental model of alzheimer’s like disease induced by aluminium lactate in rats. J App Pharmac Sci 2017; 7: 070-076. 56. Song J. Animal model of aluminum-induced alzheimer’s disease. Adv Exp Med Biol Actions 2018; 1091:113-127. 57. Yaseen AA, Al-Okbi SY, Hussein AMS, Mohamed DA, Mohammad AA, Fouda KA, et al. Potential protection from Alzheimer’s disease by wheat germ and rice bran nano-form in rat model. J Appl Pharm Sci 2019; 9: 67-76. 58. Chiroma SM, Mohd Moklas MA, Mat Taib CN, Baharuldin MTH, Amon Z. D galactose and aluminium chloride induced rat model with cognitive impairments. Biomed Pharmacother 2018; 103: 1602-1608. 59. ELBini-Dhouib I, Annabi A, Doghri R, Rejeb I, Dallagi Y, Bdiri Y, et al. Neuroprotective effects of curcumin against acetamiprid-induced neurotoxicity and oxidative stress in the developing male rat cerebellum: Biochemical, histological, and behavioral changes. Environ Sci Pollut Res Int 2017; 24: 27515-27524. 60. Zhang J, Li X. Intramolecular hydrogen bonding, π-π stacking interactions, and substituent effects of 8-hydroxyquinoline derivative supermolecular structures: A theoretical study. J Mol Model 2019; 25: 241. 61. Yamamoto S, Kayama T, Noguchi-Shinohara M, Hamaguchi T, Priyadarsini KI. The chemistry of curcumin: From extraction to therapeutic agent. Molecules 2014; 19: 20091-2112. 62. Sadegh MS, Izadi Zh, Azadi A, Kurd M, Derakhshankhah H, Sharifzadeh M, et al. Neuroprotective potential of curcumin-loaded nanostructured lipid carrier in an animal model of alzheimer’s disease: Behavioral and biochemical evidence. J Alzheimers Dis 2019; 69: 671-686. 63. ELBini-Dhouib I, Doghri R, Ellefi A, Degrach I, Srairi-Abid N, Gati A, et al. Curcumin attenuated neurotoxicity in sporadic animal model of alzheimer’s disease. Molecules 2021; 26: 3011-3025. 64. Farkhondeh, T, Ashrafizadeh M, Azimi-Nezhad M, Samini F, Aschner M, Samarghandian S, et al. Curcumin efficacy in a serum/glucose deprivation-induced neuronal pc12 injury model. Curr Mol Pharmacol 2021; 14: 1146-1155. 65. Ying X, Yu K, Chen X, Chen H, Hong J, Cheng Sh, et al. Piperine inhibits LPS induced expression of inflammatory mediators in RAW 264.7 cells. Cell Immunol 2013; 285: 49-54. 66. Chonpathompikunlert P, Wattanathorn J, Muchimapura S. The main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer’s disease. Food Chem Toxicol 2010; 48: 798-802. 67. Subedee, L, Suresh RN, Jayanthi Mk, Kalabharathi H, Satish Am, Pushpa Vh, et al. Preventive role of Indian black pepper in animal models of Alzheimer’s disease. J Clin Diagn Res 2015; 9: FF01-4. 68. Yamamoto S, Kayama T, Noguchi-Shinohara M, Hamaguchi T, Yamada M, Abe K, et al. Rosmarinic acid suppresses tau phosphorylation and cognitive decline by downregulating the JNK signaling pathway. NPJ Sci Food 2021; 5: 1-11. 69. Hase T, Shishido S, Yamamoto S, Yamashita R, Nukima H, Taira Sh, et al. Rosmarinic acid suppresses Alzheimer’s disease development by reducing amyloid β aggregation by increasing monoamine secretion. Sci Rep 2019; 9: 8711-23. 70. Lee EH, Lim SS, Yuen KH, Lee CY. Curcumin and a hemi-analogue with improved blood-brain barrier permeability protect against amyloid-beta toxicity in Caenorhabditis elegans via SKN-1/Nrf activation. J Pharm Pharmacol 2019; 71:860-868. 71. Wong, K, Roy J, Fung ML, Heng BC, Zhang Ch, Lim LW. Relationships between mitochondrial dysfunction and neurotransmission failure in Alzheimer’s disease. Aging Dis 2020; 11: 1291-1316. 72. Ayaz M, Junaid M, Ullah F, Subhan F, Sadiq A, Ali G, et al. Anti-Alzheimer’s studies on β-sitosterol isolated from Polygonum hydropiper L. Front Pharmacol 2017; 8: 697-712. 73. Sayas CL, Ávila J. GSK-3 and Tau: A key duet in Alzheimer’s disease. Cells 2021; 10: 721-740. 74. Lin R, Jones NC, Kwan P. Unravelling the role of glycogen synthase kinase-3 in Alzheimer’s disease-related epileptic seizures. Int J Mol Sci 2020; 21: 3676-3688. 75. Triaca V, Ruberti F, Canu N. NGF and the amyloid precursor protein in Alzheimer’s disease: from molecular players to neuronal circuits. Adv Exp Med Biol 2021; 1331:145-165. 76. Wu J, Yang Y, Wan Y, Xia J, Xu JF, Zhang L, et al. New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer’s disease. Biomed Pharmacother 2022; 152: 113207-227. 77. Llorens-Martín M, Jurado J, Hernández F, Avila J. GSK-3β, a pivotal kinase in Alzheimer disease. Front Mol Neurosci 2014; 7: 46-56. 78. Koistinaho J, Malm T, Goldsteins G. Glycogen synthase kinase-3β: A mediator of inflammation in Alzheimer’s disease? Int J Alzheimers Dis 2011; 2011:129753. 79. Wadhwa P, Jain P, Jadhav HR. Glycogen synthase kinase 3 (GSK3): Its role and inhibitors. Curr Top Med Chem 2020; 20: 1522-1534. | ||
|
آمار تعداد مشاهده مقاله: 461 تعداد دریافت فایل اصل مقاله: 288 |
||