Therapeutic Potential of Ascorbic Acid in the Management of Alzheimer's Disease: An Update

Nichols, E.; Steinmetz, J.D.; Vollset, S.E.; Fukutaki, K.; Chalek, J.; Abd-Allah, F.; Abdoli, A.; Abualhasan, A.; Abu-Gharbieh, E.; Akram, T.T.; Al Hamad, H.; Alahdab, F.; Alanezi, F.M.; Alipour, V.; Almustanyir, S.; Amu, H.; Ansari, I.; Arabloo, J.; Ashraf, T.; Astell-Burt, T.; Ayano, G.; Ayuso-Mateos, J.L.; Baig, A.A.; Barnett, A.; Barrow, A.; Baune, B.T.; Béjot, Y.; Bezabhe, W.M.M.; Bezabih, Y.M.; Bhagavathula, A.S.; Bhaskar, S.; Bhattacharyya, K.; Bijani, A.; Biswas, A.; Bolla, S.R.; Boloor, A.; Brayne, C.; Brenner, H.; Burkart, K.; Burns, R.A.; Cámera, L.A.; Cao, C.; Carvalho, F.; Castro-de-Araujo, L.F.S.; Catalá-López, F.; Cerin, E.; Chavan, P.P.; Cherbuin, N.; Chu, D-T.; Costa, V.M.; Couto, R.A.S.; Dadras, O.; Dai, X.; Dandona, L.; Dandona, R.; De la Cruz-Góngora, V.; Dhamnetiya, D.; Dias da Silva, D.; Diaz, D.; Douiri, A.; Edvardsson, D.; Ekholuenetale, M.; El Sayed, I.; El-Jaafary, S.I.; Eskandari, K.; Eskandarieh, S.; Esmaeilnejad, S.; Fares, J.; Faro, A.; Farooque, U.; Feigin, V.L.; Feng, X.; Fereshtehnejad, S-M.; Fernandes, E.; Ferrara, P.; Filip, I.; Fillit, H.; Fischer, F.; Gaidhane, S.; Galluzzo, L.; Ghashghaee, A.; Ghith, N.; Gialluisi, A.; Gilani, S.A.; Glavan, I-R.; Gnedovskaya, E.V.; Golechha, M.; Gupta, R.; Gupta, V.B.; Gupta, V.K.; Haider, M.R.; Hall, B.J.; Hamidi, S.; Hanif, A.; Hankey, G.J.; Haque, S.; Hartono, R.K.; Hasaballah, A.I.; Hasan, M.T.; Hassan, A.; Hay, S.I.; Hayat, K.; Hegazy, M.I.; Heidari, G.; Heidari-Soureshjani, R.; Herteliu, C.; Househ, M.; Hussain, R.; Hwang, B-F.; Iacoviello, L.; Iavicoli, I.; Ilesanmi, O.S.; Ilic, I.M.; Ilic, M.D.; Irvani, S.S.N.; Iso, H.; Iwagami, M.; Jabbarinejad, R.; Jacob, L.; Jain, V.; Jayapal, S.K.; Jayawardena, R.; Jha, R.P.; Jonas, J.B.; Joseph, N.; Kalani, R.; Kandel, A.; Kandel, H.; Karch, A.; Kasa, A.S.; Kassie, G.M.; Keshavarz, P.; Khan, M.A.B.; Khatib, M.N.; Khoja, T.A.M.; Khubchandani, J.; Kim, M.S.; Kim, Y.J.; Kisa, A.; Kisa, S.; Kivimäki, M.; Koroshetz, W.J.; Koyanagi, A.; Kumar, G.A.; Kumar, M.; Lak, H.M.; Leonardi, M.; Li, B.; Lim, S.S.; Liu, X.; Liu, Y.; Logroscino, G.; Lorkowski, S.; Lucchetti, G.; Lutzky Saute, R.; Magnani, F.G.; Malik, A.A.; Massano, J.; Mehndiratta, M.M.; Menezes, R.G.; Meretoja, A.; Mohajer, B.; Mohamed Ibrahim, N.; Mohammad, Y.; Mohammed, A.; Mokdad, A.H.; Mondello, S.; Moni, M.A.A.; Moniruzzaman, M.; Mossie, T.B.; Nagel, G.; Naveed, M.; Nayak, V.C.; Neupane Kandel, S.; Nguyen, T.H.; Oancea, B.; Otstavnov, N.; Otstavnov, S.S.; Owolabi, M.O.; Panda-Jonas, S.; Pashazadeh Kan, F.; Pasovic, M.; Patel, U.K.; Pathak, M.; Peres, M.F.P.; Perianayagam, A.; Peterson, C.B.; Phillips, M.R.; Pinheiro, M.; Piradov, M.A.; Pond, C.D.; Potashman, M.H.; Pottoo, F.H.; Prada, S.I.; Radfar, A.; Raggi, A.; Rahim, F.; Rahman, M.; Ram, P.; Ranasinghe, P.; Rawaf, D.L.; Rawaf, S.; Rezaei, N.; Rezapour, A.; Robinson, S.R.; Romoli, M.; Roshandel, G.; Sahathevan, R.; Sahebkar, A.; Sahraian, M.A.; Sathian, B.; Sattin, D.; Sawhney, M.; Saylan, M.; Schiavolin, S.; Seylani, A.; Sha, F.; Shaikh, M.A.; Shaji, K.S.; Shannawaz, M.; Shetty, J.K.; Shigematsu, M.; Shin, J.I.; Shiri, R.; Silva, D.A.S.; Silva, J.P.; Silva, R.; Singh, J.A.; Skryabin, V.Y.; Skryabina, A.A.; Smith, A.E.; Soshnikov, S.; Spurlock, E.E.; Stein, D.J.; Sun, J.; Tabarés-Seisdedos, R.; Thakur, B.; Timalsina, B.; Tovani-Palone, M.R.; Tran, B.X.; Tsegaye, G.W.; Valadan Tahbaz, S.; Valdez, P.R.; Venketasubramanian, N.; Vlassov, V.; Vu, G.T.; Vu, L.G.; Wang, Y-P.; Wimo, A.; Winkler, A.S.; Yadav, L.; Yahyazadeh Jabbari, S.H.; Yamagishi, K.; Yang, L.; Yano, Y.; Yonemoto, N.; Yu, C.; Yunusa, I.; Zadey, S.; Zastrozhin, M.S.; Zastrozhina, A.; Zhang, Z-J.; Murray, C.J.L.; Vos, T. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019. Lancet Public Health, 2022, 7(2), e105-e125.
[http://dx.doi.org/10.1016/S2468-2667(21)00249-8] [PMID: 34998485]

Varshney, V.; Garabadu, D. Ang(1–7) exerts Nrf2-mediated neuroprotection against amyloid beta-induced cognitive deficits in rodents. Mol. Biol. Rep., 2021, 48(5), 4319-4331.
[http://dx.doi.org/10.1007/s11033-021-06447-1] [PMID: 34075536]

World Health Organization. Global status report on the public health response to dementia. 2021. Available From: https://www.who.int/publications/i/item/9789240033245

Bloom, D.E. 7 billion and counting. Science, 2011, 333(6042), 562-569.
[http://dx.doi.org/10.1126/science.1209290] [PMID: 21798935]

Kaitelidou, D.; Kalogeropoulou, M.; Mougias, A.; Galanis, P.; Kontodimopoulos, N.; Pasaloglou, S.; Siskou, O. Socio-economic impact of Alzheimer’s disease in Greece: Pilot Study. Value Health, 2013, 16(7), A545.
[http://dx.doi.org/10.1016/j.jval.2013.08.1394]

Thomas, P.; Lalloué, F.; Preux, P.M.; Hazif-Thomas, C.; Pariel, S.; Inscale, R.; Belmin, J.; Clément, J.P. Dementia patients caregivers quality of life: The PIXEL study. Int. J. Geriatr. Psychiatry, 2006, 21(1), 50-56.
[http://dx.doi.org/10.1002/gps.1422] [PMID: 16323256]

Romero-Mas, M.; Ramon-Aribau, A.; Souza, D.L.B.; Cox, A.M.; Gómez-Zúñiga, B. Improving the quality of life of family caregivers of people with Alzheimer’s disease through virtual communities of practice: A quasi-experimental study. Int. J. Alzheimers Dis., 2021, 2021, 1-10.
[http://dx.doi.org/10.1155/2021/8817491] [PMID: 33884204]

Sheppard, O.; Coleman, M. Alzheimer’s disease: Etiology, neuropathology and pathogenesis. Exon Publications., 2020, 19, 1-21.
[PMID: 33400468]

Liu, S.; Liu, Y.; Hao, W.; Wolf, L.; Kiliaan, A.J.; Penke, B.; Rübe, C.E.; Walter, J.; Heneka, M.T.; Hartmann, T.; Menger, M.D.; Fassbender, K. TLR2 is a primary receptor for Alzheimer’s amyloid β peptide to trigger neuroinflammatory activation. J. Immunol., 2012, 188(3), 1098-1107.
[http://dx.doi.org/10.4049/jimmunol.1101121] [PMID: 22198949]

Kametani, F.; Hasegawa, M. Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer’s disease. Front. Neurosci., 2018, 12, 25.
[http://dx.doi.org/10.3389/fnins.2018.00025] [PMID: 29440986]

Harrison, F.E.; May, J.M. Vitamin C function in the brain: Vital role of the ascorbate transporter SVCT2. Free Radic. Biol. Med., 2009, 46(6), 719-730.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.12.018] [PMID: 19162177]

Figueroa-Méndez, R.; Rivas-Arancibia, S. Vitamin C in health and disease: Its role in the metabolism of cells and redox state in the brain. Front. Physiol., 2015, 6, 397.
[http://dx.doi.org/10.3389/fphys.2015.00397] [PMID: 26779027]

Padayatty, S.J.; Levine, M.; Vitamin, C. The known and the unknown and Goldilocks. Oral Dis., 2016, 22(6), 463-493.
[http://dx.doi.org/10.1111/odi.12446] [PMID: 26808119]

Travica, N.; Ried, K.; Sali, A.; Scholey, A.; Hudson, I.; Pipingas, A. Vitamin C status and cognitive function: A systematic review. Nutrients, 2017, 9(9), 960.
[http://dx.doi.org/10.3390/nu9090960] [PMID: 28867798]

Harrison, F.; Bowman, G.; Polidori, M. Ascorbic acid and the brain: Rationale for the use against cognitive decline. Nutrients, 2014, 6(4), 1752-1781.
[http://dx.doi.org/10.3390/nu6041752] [PMID: 24763117]

Walcher, T.; Haenle, M.M.; Kron, M.; Hay, B.; Mason, R.A.; Walcher, D.; Steinbach, G.; Kern, P.; Piechotowski, I.; Adler, G.; Boehm, B.O.; Koenig, W.; Kratzer, W. Vitamin C supplement use may protect against gallstones: An observational study on a randomly selected population. BMC Gastroenterol., 2009, 9(1), 74.
[http://dx.doi.org/10.1186/1471-230X-9-74] [PMID: 19814821]

Gupta, P.; Tiwari, S.; Haria, J. Relationship between depression and vitamin C status: A study on rural patients from western Uttar Pradesh in India. Int. J. Sci. Res., 2014, 1(4), 37-39.

Hansen, S.; Tveden-Nyborg, P.; Lykkesfeldt, J. Does vitamin C deficiency affect cognitive development and function? Nutrients, 2014, 6(9), 3818-3846.
[http://dx.doi.org/10.3390/nu6093818] [PMID: 25244370]

Nazari, H.; Heydarpoor, S.; Mohamadi Mofrad, A.; Nazari, Y.; Nazari, A. Effect of vitamin c on serum concentration of brain-derived neurotrophic factor among healthy inactive young men. Neurosci J Shefaye Khatam, 2016, 4(2), 27-32.
[http://dx.doi.org/10.18869/acadpub.shefa.4.2.27]

Nishikimi, M.; Yagi, K. Biochemistry and molecular biology of ascorbic acid biosynthesis. Subcellular Biochemistry; Springer: Cham, 1996.
[http://dx.doi.org/10.1007/978-1-4613-0325-1_2]

Devaki, S.J.; Raveendran, R.L. Vitamin C: Sources, functions, sensing and analysis. Vitamin C; Vitamin, C; Ed.; Intech Open: London, 2017.
[http://dx.doi.org/10.5772/intechopen.70162]

Siqueira, I.R.; Elsner, V.R.; Leite, M.C.; Vanzella, C.; Moysés, F.S.; Spindler, C.; Godinho, G.; Battú, C.; Wofchuk, S.; Souza, D.O.; Gonçalves, C.A.; Netto, C.A. Ascorbate uptake is decreased in the hippocampus of ageing rats. Neurochem. Int., 2011, 58(4), 527-532.
[http://dx.doi.org/10.1016/j.neuint.2011.01.011] [PMID: 21238526]

Rice, M.E. Ascorbate regulation and its neuroprotective role in the brain. Trends Neurosci., 2000, 23(5), 209-216.
[http://dx.doi.org/10.1016/S0166-2236(99)01543-X] [PMID: 10782126]

Ashor, A.W.; Siervo, M.; Mathers, J.C. Vitamin C, antioxidant status, and cardiovascular aging. Molecular basis of nutrition and aging; Academic Press: Massachusetts, 2016, pp. 609-619.
[http://dx.doi.org/10.1016/B978-0-12-801816-3.00043-1]

Ma, N.; Jie, H.; Liu, Y.; Dana, B.; Siegfried, C.J.; Beebe, D.C.; Shui, Y.B. Ascorbic acid related transporters SVCT2 and GLUT1 in human and mouse eyes. Invest. Ophthalmol. Vis. Sci., 2015, 56(7), 4671.

May, J.M. Vitamin C transport and its role in the central nervous system. Subcell. Biochem., 2012, 56, 85-103.
[http://dx.doi.org/10.1007/978-94-007-2199-9_6] [PMID: 22116696]

Bowman, G.L.; Dodge, H.; Frei, B.; Calabrese, C.; Oken, B.S.; Kaye, J.A.; Quinn, J.F. Ascorbic acid and rates of cognitive decline in Alzheimer’s disease. J. Alzheimers Dis., 2009, 16(1), 93-98.
[http://dx.doi.org/10.3233/JAD-2009-0923] [PMID: 19158425]

Frei, B. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am. J. Clin. Nutr., 1991, 54(6)(Suppl.), 1113S-1118S.
[http://dx.doi.org/10.1093/ajcn/54.6.1113s] [PMID: 1962556]

Huang, W.J.; Zhang, X.; Chen, W.W. Role of oxidative stress in Alzheimer’s disease. Biomed. Rep., 2016, 4(5), 519-522.
[http://dx.doi.org/10.3892/br.2016.630] [PMID: 27123241]

Mosoni, L.; Breuillé, D.; Buffière, C.; Obled, C.; Mirand, P.P. Age-related changes in glutathione availability and skeletal muscle carbonyl content in healthy rats. Exp. Gerontol., 2004, 39(2), 203-210.
[http://dx.doi.org/10.1016/j.exger.2003.10.014] [PMID: 15036413]

Qiu, S.; Li, L.; Weeber, E.J.; May, J.M. Ascorbate transport by primary cultured neurons and its role in neuronal function and protection against excitotoxicity. J. Neurosci. Res., 2007, 85(5), 1046-1056.
[http://dx.doi.org/10.1002/jnr.21204] [PMID: 17304569]

Lykkesfeldt, J.; Tveden-Nyborg, P. The pharmacokinetics of vitamin C. Nutrients, 2019, 11(10), 2412.
[http://dx.doi.org/10.3390/nu11102412] [PMID: 31601028]

Lindblad, M.; Tveden-Nyborg, P.; Lykkesfeldt, J. Regulation of vitamin C homeostasis during deficiency. Nutrients, 2013, 5(8), 2860-2879.
[http://dx.doi.org/10.3390/nu5082860] [PMID: 23892714]

Levine, M.; Conry-Cantilena, C.; Wang, Y.; Welch, R.W.; Washko, P.W.; Dhariwal, K.R.; Park, J.B.; Lazarev, A.; Graumlich, J.F.; King, J.; Cantilena, L.R. Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. USA, 1996, 93(8), 3704-3709.
[http://dx.doi.org/10.1073/pnas.93.8.3704] [PMID: 8623000]

Levine, M.; Wang, Y.; Padayatty, S.J.; Morrow, J. A new recommended dietary allowance of vitamin C for healthy young women. Proc. Natl. Acad. Sci. USA, 2001, 98(17), 9842-9846.
[http://dx.doi.org/10.1073/pnas.171318198] [PMID: 11504949]

Rajat, S.; Thanawala, S.; Abiraamasundari, R. Pharmacokinetics of a novel sustained-release vitamin C oral tablet: a single dose, randomized, double-blind, placebo-controlled trial. J. Pharmacol. Pharmacother., 2022, 13(2), 167-174.
[http://dx.doi.org/10.1177/0976500X221111669]

Nielsen, T.K.; Højgaard, M.; Andersen, J.T.; Poulsen, H.E.; Lykkesfeldt, J.; Mikines, K.J. Elimination of ascorbic acid after high-dose infusion in prostate cancer patients: A pharmacokinetic evaluation. Basic Clin. Pharmacol. Toxicol., 2015, 116(4), 343-348.
[http://dx.doi.org/10.1111/bcpt.12323] [PMID: 25220574]

Carr, A.C.; Lykkesfeldt, J. Discrepancies in global vitamin C recommendations: A review of RDA criteria and underlying health perspectives. Crit. Rev. Food Sci. Nutr., 2021, 61(5), 742-755.
[http://dx.doi.org/10.1080/10408398.2020.1744513] [PMID: 32223303]

Padayatty, S.J.; Sun, A.Y.; Chen, Q.; Espey, M.G.; Drisko, J.; Levine, M.; Vitamin, C. Intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One, 2010, 5(7), e11414.
[http://dx.doi.org/10.1371/journal.pone.0011414] [PMID: 20628650]

Knight, J.; Madduma-Liyanage, K.; Mobley, J.A.; Assimos, D.G.; Holmes, R.P. Ascorbic acid intake and oxalate synthesis. Urolithiasis, 2016, 44(4), 289-297.
[http://dx.doi.org/10.1007/s00240-016-0868-7] [PMID: 27002809]

Traxer, O.; Huet, B.; Poindexter, J.; Pak, C.C.; Pearle, M.S. Effect of ascorbic acid consumption on urinary stone risk factors. J. Urol., 2003, 170(2), 397-401.
[http://dx.doi.org/10.1097/01.ju.0000076001.21606.53] [PMID: 12853784]

Taylor, E.N.; Stampfer, M.J.; Curhan, G.C. Dietary factors and the risk of incident kidney stones in men: New insights after 14 years of follow-up. J. Am. Soc. Nephrol., 2004, 15(12), 3225-3232.
[http://dx.doi.org/10.1097/01.ASN.0000146012.44570.20] [PMID: 15579526]

Quinn, J.; Gerber, B.; Fouche, R.; Kenyon, K.; Blom, Z. Effect of high-dose vitamin C infusion in a glucose-6-phosphate dehydrogenase-deficient patient. Case Rep. Med., 2017, 2017, 5202606.

Pizzino, G.; Irrera, N.; Cucinotta, M.; Palio, G.; Mannino, F.; Arcoraci, V.; Squadrito, F.; Altavilla, D.; Bitto, A. Oxidative stress: Harms and benefits for human health. Oxid. Med. Cell. Longev., 2017, 2017, 8416763.
[http://dx.doi.org/10.1155/2017/8416763]

Sharifi-Rad, M.; Anil Kumar, N.V.; Zucca, P.; Varoni, E.M.; Dini, L.; Panzarini, E.; Rajkovic, J.; Tsouh Fokou, P.V.; Azzini, E.; Peluso, I.; Prakash Mishra, A.; Nigam, M.; El Rayess, Y.; Beyrouthy, M.E.; Polito, L.; Iriti, M.; Martins, N.; Martorell, M.; Docea, A.O.; Setzer, W.N.; Calina, D.; Cho, W.C.; Sharifi-Rad, J. Lifestyle, oxidative stress, and antioxidants: Back and forth in the pathophysiology of chronic diseases. Front. Physiol., 2020, 11, 694.
[http://dx.doi.org/10.3389/fphys.2020.00694] [PMID: 32714204]

Singh, A.; Kukreti, R.; Saso, L.; Kukreti, S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules, 2019, 24(8), 1583.
[http://dx.doi.org/10.3390/molecules24081583] [PMID: 31013638]

Akbar, M.; Essa, M.M.; Daradkeh, G.; Abdelmegeed, M.A.; Choi, Y.; Mahmood, L.; Song, B.J. Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress. Brain Res., 2016, 1637, 34-55.
[http://dx.doi.org/10.1016/j.brainres.2016.02.016] [PMID: 26883165]

Cheignon, C.; Tomas, M.; Bonnefont-Rousselot, D.; Faller, P.; Hureau, C.; Collin, F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol., 2018, 14, 450-464.
[http://dx.doi.org/10.1016/j.redox.2017.10.014] [PMID: 29080524]

Zhang, Y.; Thompson, R.; Zhang, H.; Xu, H. APP processing in Alzheimer’s disease. Mol. Brain, 2011, 4(1), 3.
[http://dx.doi.org/10.1186/1756-6606-4-3] [PMID: 21214928]

Haass, C.; Kaether, C.; Thinakaran, G.; Sisodia, S. Trafficking and proteolytic processing of APP. Cold Spring Harb. Perspect. Med., 2012, 2(5), a006270.
[http://dx.doi.org/10.1101/cshperspect.a006270] [PMID: 22553493]

Phillips, J.C. Why Aβ42 is much more toxic than Aβ40. ACS Chem. Neurosci., 2019, 10(6), 2843-2847.
[http://dx.doi.org/10.1021/acschemneuro.9b00068] [PMID: 31042351]

Liguori, I.; Russo, G.; Curcio, F.; Bulli, G.; Aran, L.; Della-Morte, D.; Gargiulo, G.; Testa, G.; Cacciatore, F.; Bonaduce, D.; Abete, P. Oxidative stress, aging, and diseases. Clin. Interv. Aging, 2018, 13, 757-772.
[http://dx.doi.org/10.2147/CIA.S158513] [PMID: 29731617]

Salim, S. Oxidative stress and the central nervous system. J. Pharmacol. Exp. Ther., 2017, 360(1), 201-205.
[http://dx.doi.org/10.1124/jpet.116.237503] [PMID: 27754930]

Kregel, K.C.; Zhang, H.J. An integrated view of oxidative stress in aging: Basic mechanisms, functional effects, and pathological considerations. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2007, 292(1), R18-R36.
[http://dx.doi.org/10.1152/ajpregu.00327.2006] [PMID: 16917020]

Metcalfe, M.J.; Figueiredo-Pereira, M.E. Relationship between tau pathology and neuroinflammation in Alzheimer’s disease. Mt. Sinai J. Med., 2010, 77(1), 50-58.
[http://dx.doi.org/10.1002/msj.20163] [PMID: 20101714]

Karapetyan, G.; Fereshetyan, K.; Harutyunyan, H.; Yenkoyan, K. The synergy of β amyloid 1-42 and oxidative stress in the development of Alzheimer’s disease-like neurodegeneration of hippocampal cells. Sci. Rep., 2022, 12(1), 17883.
[http://dx.doi.org/10.1038/s41598-022-22761-5] [PMID: 36284177]

Cole, S.L.; Vassar, R. The Alzheimer’s disease β-secretase enzyme, BACE1. Mol. Neurodegener., 2007, 2(1), 22.
[http://dx.doi.org/10.1186/1750-1326-2-22] [PMID: 18005427]

Jo, D.G.; Arumugam, T.V.; Woo, H.N.; Park, J.S.; Tang, S.C.; Mughal, M.; Hyun, D.H.; Park, J.H.; Choi, Y.H.; Gwon, A.R.; Camandola, S.; Cheng, A.; Cai, H.; Song, W.; Markesbery, W.R.; Mattson, M.P. Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer’s disease. Neurobiol. Aging, 2010, 31(6), 917-925.
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.07.003] [PMID: 18687504]

Scherz-Shouval, R.; Elazar, Z. Regulation of autophagy by ROS: Physiology and pathology. Trends Biochem. Sci., 2011, 36(1), 30-38.
[http://dx.doi.org/10.1016/j.tibs.2010.07.007] [PMID: 20728362]

Ighodaro, O.M.; Akinloye, O.A. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex. J. Med., 2018, 54(4), 287-293.
[http://dx.doi.org/10.1016/j.ajme.2017.09.001]

Dong, Y.; Wang, S.; Zhang, T.; Zhao, X.; Liu, X.; Cao, L.; Chi, Z. Ascorbic acid ameliorates seizures and brain damage in rats through inhibiting autophagy. Brain Res., 2013, 1535, 115-123.
[http://dx.doi.org/10.1016/j.brainres.2013.08.039] [PMID: 23994218]

Naseer, M.I.; Ullah, N.; Ullah, I.; Koh, P.O.; Lee, H.Y.; Park, M.S.; Kim, M.O. Vitamin C protects against ethanol and PTZ-induced apoptotic neurodegeneration in prenatal rat hippocampal neurons. Synapse, 2011, 65(7), 562-571.
[http://dx.doi.org/10.1002/syn.20875] [PMID: 20963815]

Robea, M.A.; Jijie, R.; Nicoara, M.; Plavan, G.; Ciobica, A.S.; Solcan, C.; Audira, G.; Hsiao, C.D.; Strungaru, S.A. Vitamin C attenuates oxidative stress and behavioral abnormalities triggered by fipronil and pyriproxyfen insecticide chronic exposure on zebrafish juvenile. Antioxidants, 2020, 9(10), 944.
[http://dx.doi.org/10.3390/antiox9100944] [PMID: 33019596]

Hsueh, Y.J.; Meir, Y.J.J.; Yeh, L.K.; Wang, T.K.; Huang, C.C.; Lu, T.T.; Cheng, C.M.; Wu, W.C.; Chen, H.C. Topical ascorbic acid ameliorates oxidative stress-induced corneal endothelial damage via suppression of apoptosis and autophagic flux blockage. Cells, 2020, 9(4), 943.
[http://dx.doi.org/10.3390/cells9040943] [PMID: 32290365]

Chang, B.J.; Jang, B.J.; Son, T.G.; Cho, I.H.; Quan, F.S.; Choe, N.H.; Nahm, S.S.; Lee, J.H. Ascorbic acid ameliorates oxidative damage induced by maternal low-level lead exposure in the hippocampus of rat pups during gestation and lactation. Food Chem. Toxicol., 2012, 50(2), 104-108.
[http://dx.doi.org/10.1016/j.fct.2011.09.043] [PMID: 22056337]

Parle, M.; Dhingra, D. Ascorbic Acid: A promising memory-enhancer in mice. J. Pharmacol. Sci., 2003, 93(2), 129-135.
[http://dx.doi.org/10.1254/jphs.93.129] [PMID: 14578579]

Rosales-Corral, S.; Tan, D.X.; Reiter, R.J.; Valdivia-Velázquez, M.; Martínez-Barboza, G.; Pablo Acosta-Martínez, J.; Ortiz, G.G. Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid- β peptide in rat brain: A comparative, in vivo study versus vitamin C and E. J. Pineal Res., 2003, 35(2), 80-84.
[http://dx.doi.org/10.1034/j.1600-079X.2003.00057.x] [PMID: 12887649]

Ballaz, S.; Morales, I.; Rodríguez, M.; Obeso, J.A. Ascorbate prevents cell death from prolonged exposure to glutamate in an in vitro model of human dopaminergic neurons. J. Neurosci. Res., 2013, 91(12), 1609-1617.
[http://dx.doi.org/10.1002/jnr.23276] [PMID: 23996657]

Lee, K.H.; Kim, U.J.; Cha, M.; Lee, B.H. Chronic treatment of ascorbic acid leads to age-dependent neuroprotection against oxidative injury in hippocampal slice cultures. Int. J. Mol. Sci., 2021, 22(4), 1608.
[http://dx.doi.org/10.3390/ijms22041608] [PMID: 33562628]

Iqbal, K.; Grundke-Iqbal, I. Alzheimer’s disease, a multifactorial disorder seeking multitherapies. Alzheimers Dement., 2010, 6(5), 420-424.
[http://dx.doi.org/10.1016/j.jalz.2010.04.006] [PMID: 20813343]

Feng, Y.; Wang, X. Antioxidant therapies for Alzheimer’s disease. Oxid. Med. Cell. Longev., 2012, 2012, 472932.
[http://dx.doi.org/10.1155/2012/472932]

Ahmad, A.; Shah, S.A.; Badshah, H.; Kim, M.J.; Ali, T.; Yoon, G.H.; Kim, T.H.; Abid, N.B.; Rehman, S.U.; Khan, S.; Kim, M.O. Neuroprotection by vitamin C against ethanol-induced neuroinflammation associated neurodegeneration in the developing rat brain. CNS Neurol. Disord. Drug Targets, 2016, 15(3), 360-370.
[http://dx.doi.org/10.2174/1871527315666151110130139] [PMID: 26831257]

Moretti, M.; Fraga, D.B.; Rodrigues, A.L.S. Preventive and therapeutic potential of ascorbic acid in neurodegenerative diseases. CNS Neurosci. Ther., 2017, 23(12), 921-929.
[http://dx.doi.org/10.1111/cns.12767] [PMID: 28980404]

Alhusaini, A.M.; Fadda, L.M.; Alsharafi, H.; Alshamary, A.F.; Hasan, I.H. L-ascorbic acid and curcumin prevents brain damage induced via lead acetate in rats: Possible mechanisms. Dev. Neurosci., 2022, 44(2), 59-66.
[http://dx.doi.org/10.1159/000521619] [PMID: 34942627]

Covarrubias-Pinto, A.; Acuña, A.; Beltrán, F.; Torres-Díaz, L.; Castro, M. Old things new view: Ascorbic acid protects the brain in neurodegenerative disorders. Int. J. Mol. Sci., 2015, 16(12), 28194-28217.
[http://dx.doi.org/10.3390/ijms161226095] [PMID: 26633354]

Jha, M.K.; Jeon, S.; Suk, K. Glia as a link between neuroinflammation and neuropathic pain. Immune Netw., 2012, 12(2), 41-47.
[http://dx.doi.org/10.4110/in.2012.12.2.41] [PMID: 22740789]

Kwon, H.S.; Koh, S.H. Neuroinflammation in neurodegenerative disorders: The roles of microglia and astrocytes. Transl. Neurodegener., 2020, 9(1), 42.
[http://dx.doi.org/10.1186/s40035-020-00221-2] [PMID: 33239064]

Olajide, O.J.; Yawson, E.O.; Gbadamosi, I.T.; Arogundade, T.T.; Lambe, E.; Obasi, K.; Lawal, I.T.; Ibrahim, A.; Ogunrinola, K.Y. Ascorbic acid ameliorates behavioural deficits and neuropathological alterations in rat model of Alzheimer’s disease. Environ. Toxicol. Pharmacol., 2017, 50, 200-211.
[http://dx.doi.org/10.1016/j.etap.2017.02.010] [PMID: 28192749]

Wang, S.F.; Liu, X.; Ding, M.Y.; Ma, S.; Zhao, J.; Wang, Y.; Li, S. 2-O-β-d-glucopyranosyl- -ascorbic acid, a novel vitamin C derivative from Lycium barbarum, prevents oxidative stress. Redox Biol., 2019, 24, 101173.
[http://dx.doi.org/10.1016/j.redox.2019.101173] [PMID: 30903981]

Dhingra, D.; Parle, M.; Kulkarni, S.K. Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid, and metrifonate in mice. J. Med. Food, 2006, 9(2), 281-283.
[http://dx.doi.org/10.1089/jmf.2006.9.281] [PMID: 16822217]

Kara, Y.; Doguc, D.K.; Kulac, E.; Gultekin, F. Acetylsalicylic acid and ascorbic acid combination improves cognition; via antioxidant effect or increased expression of NMDARs and nAChRs? Environ. Toxicol. Pharmacol., 2014, 37(3), 916-927.
[http://dx.doi.org/10.1016/j.etap.2014.02.019] [PMID: 24699240]

Huang, J.; May, J.M. Ascorbic acid protects SH-SY5Y neuroblastoma cells from apoptosis and death induced by β-amyloid. Brain Res., 2006, 1097(1), 52-58.
[http://dx.doi.org/10.1016/j.brainres.2006.04.047] [PMID: 16725131]

Harrison, F.E.; May, J.M.; McDonald, M.P. Vitamin C deficiency increases basal exploratory activity but decreases scopolamine-induced activity in APP/PSEN1 transgenic mice. Pharmacol. Biochem. Behav., 2010, 94(4), 543-552.
[http://dx.doi.org/10.1016/j.pbb.2009.11.009] [PMID: 19941887]

Murakami, K.; Murata, N.; Ozawa, Y.; Kinoshita, N.; Irie, K.; Shirasawa, T.; Shimizu, T. Vitamin C restores behavioral deficits and amyloid-β oligomerization without affecting plaque formation in a mouse model of Alzheimer’s disease. J. Alzheimers Dis., 2011, 26(1), 7-18.
[http://dx.doi.org/10.3233/JAD-2011-101971] [PMID: 21558647]

Kook, S-Y.; Lee, K-M.; Kim, Y.; Cha, M-Y.; Kang, S.; Baik, S.H.; Lee, H.; Park, R.; Mook-Jung, I. High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice. Cell Death Dis., 2014, 5(2), e1083.
[http://dx.doi.org/10.1038/cddis.2014.26] [PMID: 24577081]

Tveden-Nyborg, P.; Johansen, L.K.; Raida, Z.; Villumsen, C.K.; Larsen, J.O.; Lykkesfeldt, J. Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs. Am. J. Clin. Nutr., 2009, 90(3), 540-546.
[http://dx.doi.org/10.3945/ajcn.2009.27954] [PMID: 19640959]

Hansen, S.; Jørgensen, J.; Nyengaard, J.; Lykkesfeldt, J.; Tveden-Nyborg, P. Early life vitamin C deficiency does not alter morphology of hippocampal CA1 pyramidal neurons or markers of synaptic plasticity in a guinea pig model. Nutrients, 2018, 10(6), 749.
[http://dx.doi.org/10.3390/nu10060749] [PMID: 29890692]

Sangeetha, A.; Mohan, S.K.; Kumaresan, M. Chronic administration of vitamin C increases cognitive function in chronic stress-induced rats. Natl. J. Physiol. Pharm. Pharmacol., 2017, 7(11), 1190-1194.

Basambombo, L.L.; Carmichael, P.H.; Côté, S.; Laurin, D. Use of vitamin E and C supplements for the prevention of cognitive decline. Ann. Pharmacother., 2017, 51(2), 118-124.
[http://dx.doi.org/10.1177/1060028016673072] [PMID: 27708183]

Scheff, S.; Price, D.A. Synaptic pathology in Alzheimer’s disease: A review of ultrastructural studies. Neurobiol. Aging, 2003, 24(8), 1029-1046.
[http://dx.doi.org/10.1016/j.neurobiolaging.2003.08.002] [PMID: 14643375]

Skaper, S.D.; Facci, L.; Zusso, M.; Giusti, P. Synaptic Plasticity, Dementia and Alzheimer Disease. CNS Neurol. Disord. Drug Targets, 2017, 16(3), 220-233.
[http://dx.doi.org/10.2174/1871527316666170113120853] [PMID: 28088900]

Sattari, S.; Vaezi, G.; Shahidi, S.; Hojati, V.; Komaki, A. Protective effects of oral vitamin c on memory and learning impairment and attenuation of synaptic plasticity induced by intracerebroventricular injection of beta-amyloid peptide in male rats. Res. Sq., 2021, 1, 587881.
[http://dx.doi.org/10.21203/rs.3.rs-587881/v1]

Heruye, S.H.; Warren, T.J.; Kostansek, J.A., IV; Draves, S.B.; Matthews, S.A.; West, P.J.; Simeone, K.A.; Simeone, T.A. Ascorbic acid reduces neurotransmission, synaptic plasticity, and spontaneous hippocampal rhythms in in vitro slices. Nutrients, 2022, 14(3), 613.
[http://dx.doi.org/10.3390/nu14030613] [PMID: 35276972]

Craig, A.; Guest, R.; Tran, Y.; Middleton, J. Cognitive impairment and mood states after spinal cord injury. J. Neurotrauma, 2017, 34(6), 1156-1163.
[http://dx.doi.org/10.1089/neu.2016.4632] [PMID: 27717295]

Chen, C; Yang, Q; Ma, X Synergistic effect of ascorbic acid and taurine in the treatment of a spinal cord injury-induced model in rats. 3 Biotech, 2020, 10, 1-8.

Adebiyi, O.; Adigun, K.; David-Odewumi, P.; Akindele, U.; Olayemi, F. Gallic and ascorbic acids supplementation alleviate cognitive deficits and neuropathological damage exerted by cadmium chloride in Wistar rats. Sci. Rep., 2022, 12(1), 14426.
[http://dx.doi.org/10.1038/s41598-022-18432-0] [PMID: 36002551]

Singh, N.K.; Garabadu, D. Quercetin exhibits α7nAChR/Nrf2/HO-1-mediated neuroprotection against STZ-induced mitochondrial toxicity and cognitive impairments in experimental rodents. Neurotox. Res., 2021, 39(6), 1859-1879.
[http://dx.doi.org/10.1007/s12640-021-00410-5] [PMID: 34554409]

Yamamoto, M.; Kensler, T.W.; Motohashi, H. The KEAP1-NRF2 system: A thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiol. Rev., 2018, 98(3), 1169-1203.
[http://dx.doi.org/10.1152/physrev.00023.2017] [PMID: 29717933]

He, F.; Ru, X.; Wen, T. NRF2, a transcription factor for stress response and beyond. Int. J. Mol. Sci., 2020, 21(13), 4777.
[http://dx.doi.org/10.3390/ijms21134777] [PMID: 32640524]

Jaganjac, M.; Milkovic, L.; Sunjic, S.B.; Zarkovic, N. The NRF2, thioredoxin, and glutathione system in tumorigenesis and anticancer therapies. Antioxidants, 2020, 9(11), 1151.
[http://dx.doi.org/10.3390/antiox9111151] [PMID: 33228209]

Gan, L.; Johnson, J.A. Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases. Biochim. Biophys. Acta Mol. Basis Dis., 2014, 1842(8), 1208-1218.
[http://dx.doi.org/10.1016/j.bbadis.2013.12.011] [PMID: 24382478]

Zhang, L.; Ma, Q.; Zhou, Y. Strawberry leaf extract treatment alleviates cognitive impairment by activating Nrf2/HO-1 signaling in rats with streptozotocin-induced diabetes. Front. Aging Neurosci., 2020, 12, 201.
[http://dx.doi.org/10.3389/fnagi.2020.00201] [PMID: 32792939]

Wu, L.; Xu, W.; Li, H.; Dong, B.; Geng, H.; Jin, J.; Han, D.; Liu, H.; Zhu, X.; Yang, Y.; Xie, S. Vitamin C attenuates oxidative stress, inflammation, and apoptosis induced by acute hypoxia through the Nrf2/Keap1 signaling pathway in gibel carp (Carassiusgibelio). Antioxidants, 2022, 11(5), 935.
[http://dx.doi.org/10.3390/antiox11050935] [PMID: 35624798]

Majchrzak, D.; Mitter, S.; Elmadfa, I. The effect of ascorbic acid on total antioxidant activity of black and green teas. Food Chem., 2004, 88(3), 447-451.
[http://dx.doi.org/10.1016/j.foodchem.2004.01.058]

Intra, J.; Kuo, S.M. Physiological levels of tea catechins increase cellular lipid antioxidant activity of vitamin C and vitamin E in human intestinal Caco-2 cells. Chem. Biol. Interact., 2007, 169(2), 91-99.
[http://dx.doi.org/10.1016/j.cbi.2007.05.007] [PMID: 17603031]

Traber, M.G.; Stevens, J.F. Vitamins C and E: Beneficial effects from a mechanistic perspective. Free Radic. Biol. Med., 2011, 51(5), 1000-1013.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.05.017] [PMID: 21664268]

Zhao, Y.; Pan, Y.; Tang, M.; Lin, W. Blocking p38 signaling reduces the activation of pro-inflammatory cytokines and the phosphorylation of p38 in the habenula and reverses depressive-like behaviors induced by neuroinflammation. Front. Pharmacol., 2018, 9, 511.
[http://dx.doi.org/10.3389/fphar.2018.00511] [PMID: 29867510]

Zhang, X.Y.; Xu, Z.P.; Wang, W.; Cao, J.B.; Fu, Q.; Zhao, W.X.; Li, Y.; Huo, X.L.; Zhang, L.M.; Li, Y.F.; Mi, W.D. Vitamin C alleviates LPS-induced cognitive impairment in mice by suppressing neuroinflammation and oxidative stress. Int. Immunopharmacol., 2018, 65, 438-447.
[http://dx.doi.org/10.1016/j.intimp.2018.10.020] [PMID: 30388518]

Moretti, M.; Budni, J.; Freitas, A.E.; Neis, V.B.; Ribeiro, C.M.; de Oliveira Balen, G.; Rieger, D.K.; Leal, R.B.; Rodrigues, A.L.S. TNF-α-induced depressive-like phenotype and p38MAPK activation are abolished by ascorbic acid treatment. Eur. Neuropsychopharmacol., 2015, 25(6), 902-912.
[http://dx.doi.org/10.1016/j.euroneuro.2015.03.006] [PMID: 25836357]

Radi, A.M.; Mohammed, E.T.; Abushouk, A.I.; Aleya, L.; Abdel-Daim, M.M. The effects of abamectin on oxidative stress and gene expression in rat liver and brain tissues: Modulation by sesame oil and ascorbic acid. Sci. Total Environ., 2020, 701, 134882.
[http://dx.doi.org/10.1016/j.scitotenv.2019.134882] [PMID: 31739238]

Xiao, Y.; Su, C.; Zhang, G.; Liang, L.; Jin, T.; Bradley, J.; Ornato, J.P.; Tang, W.; Vitamin, C. Vitamin C improves the outcomes of cardiopulmonary resuscitation and alters shedding of syndecan-1 and p38/MAPK phosphorylation in a rat model. J. Am. Heart Assoc., 2022, 11(7), e023787.
[http://dx.doi.org/10.1161/JAHA.121.023787] [PMID: 35289183]

Cárcamo, J.M.; Pedraza, A.; Bórquez-Ojeda, O.; Golde, D.W. Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation. Biochemistry, 2002, 41(43), 12995-13002.
[http://dx.doi.org/10.1021/bi0263210] [PMID: 12390026]

Cárcamo, J.M.; Pedraza, A.; Bórquez-Ojeda, O.; Zhang, B.; Sanchez, R.; Golde, D.W. Vitamin C is a kinase inhibitor: Dehydroascorbic acid inhibits IkappaBalpha kinase β. Mol. Cell. Biol., 2004, 24(15), 6645-6652.
[http://dx.doi.org/10.1128/MCB.24.15.6645-6652.2004] [PMID: 15254232]

Dang, W. The controversial world of sirtuins. Drug Discov. Today. Technol., 2014, 12, e9-e17.
[http://dx.doi.org/10.1016/j.ddtec.2012.08.003] [PMID: 25027380]

Costa, L.G.; Garrick, J.M.; Roquè, P.J.; Pellacani, C. Mechanisms of neuroprotection by quercetin: Counteracting oxidative stress and more. Oxid. Med. Cell. Longev., 2016, 12016, 2986796.
[http://dx.doi.org/10.1155/2016/2986796]

Wei, W.; Li, L.; Zhang, Y. Geriletu; Yang, J.; Zhang, Y.; Xing, Y. Vitamin C protected human retinal pigmented epithelium from oxidant injury depending on regulating SIRT1. ScientificWorldJournal, 2014, 2014, 1-8.
[http://dx.doi.org/10.1155/2014/750634] [PMID: 25147862]

Nam, S.; Seo, M.; Seo, J.S.; Rhim, H.; Nahm, S.S.; Cho, I.H.; Chang, B.J.; Kim, H.J.; Choi, S.H.; Nah, S.Y. Ascorbic acid mitigates D-galactose-induced brain aging by increasing hippocampal neurogenesis and improving memory function. Nutrients, 2019, 11(1), 176.
[http://dx.doi.org/10.3390/nu11010176] [PMID: 30650605]

Martin, A.; Joseph, J.A.; Cuervo, A.M. Stimulatory effect of vitamin C on autophagy in glial cells. J. Neurochem., 2002, 82(3), 538-549.
[http://dx.doi.org/10.1046/j.1471-4159.2002.00978.x] [PMID: 12153478]

Chen, Y.; Luo, G.; Yuan, J.; Wang, Y.; Yang, X.; Wang, X.; Li, G.; Liu, Z.; Zhong, N. Vitamin C mitigates oxidative stress and tumor necrosis factor-alpha in severe community-acquired pneumonia and LPS-induced macrophages. Mediators Inflamm., 2014, 2014, 426740.

Huang, Y.N.; Yang, L.Y.; Wang, J.Y.; Lai, C.C.; Chiu, C.T.; Wang, J.Y. L-Ascorbate protects against methamphetamine-induced neurotoxicity of cortical cells via inhibiting oxidative stress, autophagy, and apoptosis. Mol. Neurobiol., 2017, 54(1), 125-136.
[http://dx.doi.org/10.1007/s12035-015-9561-z] [PMID: 26732595]

Morris, M.C.; Evans, D.A.; Tangney, C.C.; Bienias, J.L.; Wilson, R.S.; Aggarwal, N.T.; Scherr, P.A. Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am. J. Clin. Nutr., 2005, 81(2), 508-514.
[http://dx.doi.org/10.1093/ajcn.81.2.508] [PMID: 15699242]

Arlt, S.; Müller-Thomsen, T.; Beisiegel, U.; Kontush, A. Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer’s disease. Neurochem. Res., 2012, 37(12), 2706-2714.
[http://dx.doi.org/10.1007/s11064-012-0860-8] [PMID: 22878647]

Galasko, D.R.; Peskind, E.; Clark, C.M.; Quinn, J.F.; Ringman, J.M.; Jicha, G.A.; Cotman, C.; Cottrell, B.; Montine, T.J.; Thomas, R.G.; Aisen, P. Antioxidants for Alzheimer disease: A randomized clinical trial with cerebrospinal fluid biomarker measures. Arch. Neurol., 2012, 69(7), 836-841.
[http://dx.doi.org/10.1001/archneurol.2012.85] [PMID: 22431837]

Ulstein, I.; Bøhmer, T. Normal vitamin levels and nutritional indices in Alzheimer’s disease patients with mild cognitive impairment or dementia with normal body mass indexes. J. Alzheimers Dis., 2016, 55(2), 717-725.
[http://dx.doi.org/10.3233/JAD-160393] [PMID: 27716664]

Polidori, M.; Nelles, G. Antioxidant clinical trials in mild cognitive impairment and Alzheimer’s disease - challenges and perspectives. Curr. Pharm. Des., 2014, 20(18), 3083-3092.
[http://dx.doi.org/10.2174/13816128113196660706] [PMID: 24079767]

Li, Y.; Liu, S.; Man, Y.; Li, N.; Zhou, Y. Effects of vitamins E and C combined with β-carotene on cognitive function in the elderly. Exp. Ther. Med., 2015, 9(4), 1489-1493.
[http://dx.doi.org/10.3892/etm.2015.2274] [PMID: 25780457]

Travica, N.; Ried, K.; Sali, A.; Hudson, I.; Scholey, A.; Pipingas, A. Plasma vitamin C concentrations and cognitive function: A cross-sectional study. Front. Aging Neurosci., 2019, 11, 72.
[http://dx.doi.org/10.3389/fnagi.2019.00072] [PMID: 31001107]

Khodaie, M.; Alibeigi, N.; Mirzaei, V.G. The effect of Ascorbic Acid as supplementary treatment with risperidone in controlling the symptoms of schizophrenia: A double-blind, placebo-controlled clinical trial. J Basic Clin Pathophysiol., 2019, 7(1), 7-14.

Sharma, Y.; Popescu, A.; Horwood, C.; Hakendorf, P.; Thompson, C. Relationship between vitamin C deficiency and cognitive impairment in older hospitalised patients: A cross-sectional study. Antioxidants, 2022, 11(3), 463.
[http://dx.doi.org/10.3390/antiox11030463] [PMID: 35326113]

Sim, M.; Hong, S.; Jung, S.; Kim, J.S.; Goo, Y.T.; Chun, W.Y.; Shin, D.M. Vitamin C supplementation promotes mental vitality in healthy young adults: Results from a cross-sectional analysis and a randomized, double-blind, placebo-controlled trial. Eur. J. Nutr., 2022, 61(1), 447-459.
[http://dx.doi.org/10.1007/s00394-021-02656-3] [PMID: 34476568]

Lanyau-Domínguez, Y.; Macías-Matos, C.; Jesús, J.; María, G.; Suárez-Medina, R.; Eugenia, M.; Noriega-Fernández, L.; Guerra-Hernández, M.; Calvo-Rodríguez, M.; Sánchez-Gil, Y.; García-Klibanski, M.; Herrera-Javier, D.; Arocha-Oriol, C.; Díaz-Domínguez, M. Levels of vitamins and homocysteine in older adults with Alzheimer disease or mild cognitive impairment in Cuba. MEDICC Rev., 2020, 22(4), 40-47.
[http://dx.doi.org/10.37757/MR2020.V22.N4.14] [PMID: 33295319]

Uabundit, N.; Wattanathorn, J.; Mucimapura, S.; Ingkaninan, K. Cognitive enhancement and neuroprotective effects of Bacopa monnieri in Alzheimer’s disease model. J. Ethnopharmacol., 2010, 127(1), 26-31.
[http://dx.doi.org/10.1016/j.jep.2009.09.056] [PMID: 19808086]

Akter, F.; Haque, M.; Islam, J.; Rahaman, A.; Bhowmick, S.; Hossain, S. Chronic administration of Curcuma longa extract improves spatial memory-related learning ability in aged rats by inhibiting brain cortico-hippocampal oxidative stress and TNFα. Adv. Alzheimer Dis., 2015, 4(3), 78-89.
[http://dx.doi.org/10.4236/aad.2015.43008]

Lee, J.; Torosyan, N.; Silverman, D.H. Examining the impact of grape consumption on brain metabolism and cognitive function in patients with mild decline in cognition: A double-blinded placebo controlled pilot study. Exp. Gerontol., 2017, 87(Pt A), 121-128.
[http://dx.doi.org/10.1016/j.exger.2016.10.004] [PMID: 27856335]

Alaei, H.; Pilehvarian, A.A.; Siahmard, Z.; Reisi, P. The effect of red grape juice on Alzheimer′s disease in rats. Adv. Biomed. Res., 2012, 1(1), 63.
[http://dx.doi.org/10.4103/2277-9175.100188] [PMID: 23326794]

Najwa, F.R.; Azrina, A. Comparison of vitamin C content in citrus fruits by titration and high performance liquid chromatography (HPLC) methods. Int. Food Res. J., 2017, 24(2), 726.

Semwal, B.C.; Verma, M.; Murti, Y.; Yadav, H.N. Neuroprotective activity of Sesbania grandifolara seeds extract against celecoxib induced amnesia in mice. Pharmacogn. J., 2018, 10(4), 747-752.
[http://dx.doi.org/10.5530/pj.2018.4.125]

Abu Almaaty, A.H.; Mosaad, R.M.; Hassan, M.K.; Ali, E.H.A.; Mahmoud, G.A.; Ahmed, H.; Anber, N.; Alkahtani, S.; Abdel-Daim, M.M.; Aleya, L.; Hammad, S. Urtica dioica extracts abolish scopolamine-induced neuropathies in rats. Environ. Sci. Pollut. Res. Int., 2021, 28(14), 18134-18145.
[http://dx.doi.org/10.1007/s11356-020-12025-y] [PMID: 33405105]

Jayachitra, A.; Padma, P.R. Non-enzymic antioxidant activity of Clitoria ternatea leaf extracts in vitro. Biosci. Biotechnol. Res. Asia, 2016, 7(1), 209-218.

Damodaran, T.; Tan, B.W.L.; Liao, P.; Ramanathan, S.; Lim, G.K.; Hassan, Z. Clitoria ternatea L. root extract ameliorated the cognitive and hippocampal long-term potentiation deficits induced by chronic cerebral hypoperfusion in the rat. J. Ethnopharmacol., 2018, 224, 381-390.
[http://dx.doi.org/10.1016/j.jep.2018.06.020] [PMID: 29920356]

Tan, M.A.; Sharma, N.; An, S.S.A. Multi-target approach of Murraya koenigii leaves in treating neurodegenerative diseases. Pharmaceuticals (Basel), 2022, 15(2), 188.
[http://dx.doi.org/10.3390/ph15020188] [PMID: 35215300]

Valšíková, M.; Mezeyová, I.; Rehuš, M.; Šlosár, M. Changes of vitamin C content in celery and parsley herb after processing. Potravinárstvo, 2016.

Chonpathompikunlert, P.; Boonruamkaew, P.; Sukketsiri, W.; Hutamekalin, P.; Sroyraya, M. The antioxidant and neurochemical activity of Apium graveolens L. and its ameliorative effect on MPTP-induced Parkinson-like symptoms in mice. BMC Complement. Altern. Med., 2018, 18(1), 103.
[http://dx.doi.org/10.1186/s12906-018-2166-0] [PMID: 29558946]

Ahmad, L.; Mujahid, M.; Mishra, A.; Rahman, M.A. Protective role of hydroalcoholic extract of Cajanus cajan Linn leaves against memory impairment in sleep deprived experimental rats. J. Ayurveda Integr. Med., 2020, 11(4), 471-477.
[http://dx.doi.org/10.1016/j.jaim.2018.08.003] [PMID: 30661946]

Ercisli, S.; Orhan, E. Chemical composition of white (Morus alba), red (Morus rubra) and black (Morus nigra) mulberry fruits. Food Chem., 2007, 103(4), 1380-1384.
[http://dx.doi.org/10.1016/j.foodchem.2006.10.054]

Kaewkaen, P.; Tong-un, T.; Wattanathorn, J.; Muchimapura, S.; Kaewrueng, W.; Wongcharoenwanakit, S. Mulberry fruit extract protects against memory impairment and hippocampal damage in animal model of vascular dementia. Evid. Based Complement. Alternat. Med., 2012, 2012, 1-9.
[http://dx.doi.org/10.1155/2012/263520] [PMID: 22952555]

Sadeghi-Aliabadi, H.; Momtazi-borojeni, A.A.; Rabbani, M.; Ghannadi, A.; Abdollahi, E. Cognitive enhancing of pineapple extract and juice in scopolamine-induced amnesia in mice. Res. Pharm. Sci., 2017, 12(3), 257-264.
[http://dx.doi.org/10.4103/1735-5362.207198] [PMID: 28626484]

Sarkar, T.; Salauddin, M.; Hazra, S.K.; Chakraborty, R. The impact of raw and differently dried pineapple (Ananas comosus) fortification on the vitamins, organic acid and carotene profile of dairy rasgulla (sweetened cheese ball). Heliyon, 2020, 6(10), e05233.
[http://dx.doi.org/10.1016/j.heliyon.2020.e05233] [PMID: 33102856]

Santana, L.F.; Inada, A.C.; Espirito Santo, B.L.S.; Filiú, W.F.O.; Pott, A.; Alves, F.M.; Guimarães, R.C.A.; Freitas, K.C.; Hiane, P.A. Nutraceutical potential of Carica papaya in metabolic syndrome. Nutrients, 2019, 11(7), 1608.
[http://dx.doi.org/10.3390/nu11071608] [PMID: 31315213]

Bindhu, K.H.; Vijayalakshmi, A. Neuroprotective effect of Carica papaya leaf extract against aluminium toxicity: An experimental study on cognitive dysfunction and biochemical alterations in rats. Indian J Pharmaceut Edu Res, 2019, 53(3s), s392-s398.
[http://dx.doi.org/10.5530/ijper.53.3s.111]

Chiteva, R.; Wairagu, N. Chemical and nutritional content of Opuntiaficus-indica (L.). Afr. J. Biotechnol., 2013, 12(21)

Han, E.H.; Lim, M.K.; Lee, S.; Lee, S.H.; Yun, S.M.; Yu, H.J.; Ryu, S.H.; Lim, Y.H. Efficacy of ethanolic extract of Opuntiaficus-indica var. saboten stems for improving cognitive function in elderly subjects 55–85 years of age: A randomized, double-blind, placebo-controlled study. J. Med. Food, 2020, 23(11), 1146-1154.
[http://dx.doi.org/10.1089/jmf.2019.4678] [PMID: 33006504]

Jang, H.; Srichayet, P.; Park, W.J.; Heo, H.J.; Kim, D.O.; Tongchitpakdee, S.; Kim, T.J.; Jung, S.H.; Lee, C.Y. Phyllanthus emblica L. (Indian gooseberry) extracts protect against retinal degeneration in a mouse model of amyloid beta-induced Alzheimer’s disease. J. Funct. Foods, 2017, 37, 330-338.
[http://dx.doi.org/10.1016/j.jff.2017.07.056]

Kandeda, A.K.; Nguedia, D.; Ayissi, E.R.; Kouamouo, J.; Dimo, T. Ziziphus jujuba (rhamnaceae) alleviates working memory impairment and restores neurochemical alterations in the prefrontal cortex of D-galactose-treated rats. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-15.
[http://dx.doi.org/10.1155/2021/6610864] [PMID: 34194520]

Otong, E.S.; Musa, S.A.; Danborno, B.; Sambo, S.J. Adansoniadigitata ameliorates lead-induced memory impairments in rats by reducing glutamate concentration and oxidative stress. Egypt J Basic Appl Sci., 2022, 9(1), 1-0.

Azevêdo, J.C.S.; Borges, K.C.; Genovese, M.I.; Correia, R.T.P.; Vattem, D.A. Neuroprotective effects of dried camu-camu (Myrciaria dubia HBK McVaugh) residue in C. elegans. Food Res. Int., 2015, 73, 135-141.
[http://dx.doi.org/10.1016/j.foodres.2015.02.015]

Li, H.; Lei, T.; Zhang, J.; Yan, Y.; Wang, N.; Song, C.; Li, C.; Sun, M.; Li, J.; Guo, Y.; Yang, J.; Kang, T. Longan (Dimocarpus longan Lour.) Aril ameliorates cognitive impairment in AD mice induced by combination of D-gal/AlCl3 and an irregular diet via RAS/MEK/ERK signaling pathway. J. Ethnopharmacol., 2021, 267, 113612.
[http://dx.doi.org/10.1016/j.jep.2020.113612] [PMID: 33249246]

Zhang, S.; Yu, Z.; Sun, L.; Ren, H.; Zheng, X.; Liang, S.; Qi, X. An overview of the nutritional value, health properties, and future challenges of Chinese bayberry. PeerJ, 2022, 10, e13070.
[http://dx.doi.org/10.7717/peerj.13070] [PMID: 35265403]

Cho, C.H.; Jung, Y.S.; Kim, J.M.; Nam, T.G.; Lee, S.H.; Cho, H.S.; Song, M.C.; Heo, H.J.; Kim, D.O. Neuroprotective effects of Actinidia eriantha cv. Bidan kiwifruit on amyloid beta-induced neuronal damages in PC-12 cells and ICR mice. J. Funct. Foods, 2021, 79, 104398.
[http://dx.doi.org/10.1016/j.jff.2021.104398]

Jones, J.R.; Lebar, M.D.; Jinwal, U.K.; Abisambra, J.F.; Koren, J., III; Blair, L.; O’Leary, J.C.; Davey, Z.; Trotter, J.; Johnson, A.G.; Weeber, E.; Eckman, C.B.; Baker, B.J.; Dickey, C.A. The diarylheptanoid (+)-aR,11S-myricanol and two flavones from bayberry (Myrica cerifera) destabilize the microtubule-associated protein tau. J. Nat. Prod., 2011, 74(1), 38-44.
[http://dx.doi.org/10.1021/np100572z] [PMID: 21141876]

Sato, A.; Tagai, N.; Ogino, Y.; Uozumi, H.; Kawakami, S.; Yamamoto, T.; Tanuma, S.; Maruki-Uchida, H.; Mori, S.; Morita, M. Passion fruit seed extract protects beta-amyloid-induced neuronal cell death in a differentiated human neuroblastoma SH‐SY5Y cell model. Food Sci. Nutr., 2022, 10(5), 1461-1468.
[http://dx.doi.org/10.1002/fsn3.2757] [PMID: 35592293]

Temviriyanukul, P.; Kittibunchakul, S.; Trisonthi, P.; Kunkeaw, T.; Inthachat, W.; Siriwan, D.; Suttisansanee, U. Mangifera indica ‘Namdokmai’ prevents neuronal cells from amyloid peptide toxicity and inhibits BACE-1 activities in a Drosophila model of Alzheimer’s amyloidosis. Pharmaceuticals (Basel), 2022, 15(5), 591.
[http://dx.doi.org/10.3390/ph15050591] [PMID: 35631418]