Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

A Review on Garlic as a Supplement for Alzheimer’s Disease: A Mechanistic Insight into its Direct and Indirect Effects

Author(s): Mohammad Mahdi Ghazimoradi, Mozhgan Ghobadi Pour, Ehsan Ghoushi, Hadise Karimi Ahmadabadi and Mahmoud Rafieian-Kopaei*

Volume 29, Issue 7, 2023

Published on: 15 March, 2023

Page: [519 - 526] Pages: 8

DOI: 10.2174/1381612829666230222093016

Price: $65

Abstract

Alzheimer’s disease (AD) is one of the most complicated neurodegenerative diseases causing dementia in human beings. Aside from that, the incidence of AD is increasing and its treatment is very complicated. There are several known hypotheses regarding the pathology of Alzheimer’s disease, including the amyloid beta hypothesis, tau hypothesis, inflammation hypothesis, and cholinergic hypothesis, which are investigated in different researches to completely elucidate the pathology of AD. Besides, some new mechanisms, such as immune, endocrine, and vagus pathways, as well as bacteria metabolite secretions, are being explained as other causes to be somehow related to AD pathogenesis. There is still no definite treatment for Alzheimer’s disease that can completely cure and eradicate AD. Garlic (Allium sativum) is a traditional herb used as a spice in different cultures, and due to the organosulfur compounds, like allicin, it possesses highly anti-oxidant properties; the benefits of garlic in cardiovascular diseases, like hypertension and atherosclerosis, have been examined and reviewed, although its beneficiary effects in neurodegenerative diseases, such as AD, are not completely understood. In this review, we discuss the effects of garlic based on its components, such as allicin and S-allyl cysteine, on Alzheimer’s disease and the mechanisms of garlic components that can be beneficiary for AD patients, including its effects on amyloid beta, oxidative stress, tau protein, gene expression, and cholinesterase enzymes. Based on the literature review, garlic has been revealed to have beneficiary effects on Alzheimer’s disease, especially in animal studies; however, more studies should be done on humans to find the exact mechanisms of garlic’s effects on AD patients.

Keywords: Alzheimer disease, garlic, allicin, S-allyl cysteine, amyloid beta, tau protein.

« Previous Next »
[1]
Lei P, Ayton S, Bush AI. The essential elements of Alzheimer’s disease. J Biol Chem 2021; 296: 100105.
[http://dx.doi.org/10.1074/jbc.REV120.008207] [PMID: 33219130]
[2]
World Alzheimer Report. Alzheimer’s Disease International (ADI). 2018. Available from: https://www.alzint.org/resource/world-alzheimer-report-2018/
[3]
Rhodius-Meester HFM, Tijms BM, Lemstra AW, et al. Survival in memory clinic cohort is short, even in young-onset dementia. J Neurol Neurosurg Psychiatry 2019; 90(6): 726-8.
[http://dx.doi.org/10.1136/jnnp-2018-318820] [PMID: 30045942]
[4]
Jack CR Jr, Therneau TM, Weigand SD, et al. Prevalence of biologically vs. clinically defined alzheimer spectrum entities using the national institute on aging–Alzheimer’s association research framework. JAMA Neurol 2019; 76(10): 1174-83.
[http://dx.doi.org/10.1001/jamaneurol.2019.1971] [PMID: 31305929]
[5]
Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer’s disease: The IWG-2 criteria. Lancet Neurol 2014; 13(6): 614-29.
[http://dx.doi.org/10.1016/S1474-4422(14)70090-0] [PMID: 24849862]
[6]
Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet 2006; 368(9533): 387-403.
[http://dx.doi.org/10.1016/S0140-6736(06)69113-7] [PMID: 16876668]
[7]
Lashley T, Schott JM, Weston P, Murray CE, Wellington H, Keshavan A, et al. Molecular biomarkers of Alzheimer’s disease: Progress and prospects. Dis Model Mech 2018; 11(5): dmm031781.
[http://dx.doi.org/10.1242/dmm.031781]
[8]
Chaney A, Williams SR, Boutin H. In vivo molecular imaging of neuroinflammation in Alzheimer’s disease. J Neurochem 2019; 149(4): 438-51.
[http://dx.doi.org/10.1111/jnc.14615] [PMID: 30339715]
[9]
Heneka MT, Carson MJ, Khoury J, et al. Neuroinflammation in Alzheimer’s Disease. Lancet Neurol 2015; 14(4): 388.
[http://dx.doi.org/10.1016/S1474-4422(15)70016-5]
[10]
Cao J, Hou J, Ping J, Cai D. Advances in developing novel therapeutic strategies for Alzheimer’s disease. Mol Neurodegener 2018; 13(1): 1-20.
[http://dx.doi.org/10.1186/s13024-018-0299-8]
[11]
Ozben T, Ozben S. Neuro-inflammation and anti-inflammatory treatment options for Alzheimer’s disease. Clin Biochem 2019; 72: 87-9.
[http://dx.doi.org/10.1016/j.clinbiochem.2019.04.001] [PMID: 30954437]
[12]
Lozupone M, Solfrizzi V, D’Urso F, et al. Anti-amyloid-β protein agents for the treatment of Alzheimer’s disease: An update on emerging drugs. Expert Opin Emerg Drugs 2020; 25(3): 319-35.
[http://dx.doi.org/10.1080/14728214.2020.1808621] [PMID: 32772738]
[13]
Zhu Y, Anand R, Geng X, Ding Y. A mini review: Garlic extract and vascular diseases. Neurol Res 2018; 40(6): 421-5.
[http://dx.doi.org/10.1080/01616412.2018.1451269] [PMID: 29557277]
[14]
Ray B, Chauhan NB, Lahiri DK. The “aged garlic extract”: (AGE) and one of its active ingredients S-allyl-L-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer’s disease (AD). Curr Med Chem 2011; 18(22): 3306-13.
[http://dx.doi.org/10.2174/092986711796504664] [PMID: 21728972]
[15]
Du X, Wang X, Geng M. Alzheimer’s disease hypothesis and related therapies. Transl Neurodegener 2018; 7(1): 1-7.
[http://dx.doi.org/10.1186/s40035-018-0107-y]
[16]
Gilman S, Koller M, Black RS, et al. Clinical effects of A immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005; 64(9): 1553-62.
[http://dx.doi.org/10.1212/01.WNL.0000159740.16984.3C] [PMID: 15883316]
[17]
The Lancet Neurology. Solanezumab: Too late in mild Alzheimer’s disease? Lancet Neurol 2017; 16(2): 97.
[http://dx.doi.org/10.1016/S1474-4422(16)30395-7] [PMID: 28102152]
[18]
Musiek ES, Holtzman DM. Three dimensions of the amyloid hypothesis: Time, space and “wingmen”. Nat Neurosci 2015; 18(6): 800-6.
[19]
Brier MR, Gordon B, Friedrichsen K, et al. Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease. Sci Transl Med 2016; 8(338): 338ra66.
[http://dx.doi.org/10.1126/scitranslmed.aaf2362] [PMID: 27169802]
[20]
Meyer PF, Tremblay-Mercier J, Leoutsakos J, et al. INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease. Neurology 2019; 92(18): e2070-80.
[http://dx.doi.org/10.1212/WNL.0000000000007232] [PMID: 30952794]
[21]
Belkaid Y, Harrison OJ. Homeostatic immunity and the microbiota. Immunity 2017; 46(4): 562.
[http://dx.doi.org/10.1016/j.immuni.2017.04.008]
[22]
Jiang X, Shi D, Hu S. Research progress in anti-inflammation of vagus nerve and neurotransmitter. 2003. Available from: https://europepmc.org/article/med/12852822 [Accessed on: 2022 May 13].
[23]
Das UN. Vagus nerve stimulation, depression, and inflammation. Neuropsychopharmacol 2007; 32(9): 2053-4.
[24]
Browning KN, Verheijden S, Boeckxstaens GE. The vagus nerve in appetite regulation, mood, and intestinal inflammation. Gastroenterology 2017; 152(4): 730-44.
[http://dx.doi.org/10.1053/j.gastro.2016.10.046] [PMID: 27988382]
[25]
Mitchell RW, On NH, Del Bigio MR, Miller DW, Hatch GM. Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells. J Neurochem 2011; 117(4): 735-46.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07245.x] [PMID: 21395585]
[26]
Frost G, Sleeth ML, Sahuri-Arisoylu M, Lizarbe B, Cerdan S, Brody L, et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun 5; (1): 1-11.
[http://dx.doi.org/10.1038/ncomms4611]
[27]
Quigley EMM. Microbiota-brain-gut axis and neurodegenerative diseases. Curr Neurol Neurosci Rep 2017; 17(12): 94.
[http://dx.doi.org/10.1007/s11910-017-0802-6] [PMID: 29039142]
[28]
Saini N, Kadian M. Therapeutic potential of Allium sativum against the Aβ(1-40)-induced oxidative stress and mitochondrial dysfunction in the Wistar rats. Am J Neurodegener Dis 2021; 10(2): 13.
[29]
Kaur S, Raj K, Gupta YK, Singh S. Allicin ameliorates aluminium- and copper-induced cognitive dysfunction in Wistar rats: Relevance to neuro-inflammation, neurotransmitters and Aβ(1–42) analysis. J Biol Inorg Chem 2021; 26(4): 495-510.
[http://dx.doi.org/10.1007/s00775-021-01866-8] [PMID: 34023945]
[30]
Okkay U, Ferah Okkay I. In vitro neuroprotective effects of allicin on Alzheimer’s disease model of neuroblastoma cell line. Journal of Surgery and Medicine 2022; 6(2): 209-12.
[http://dx.doi.org/10.28982/josam.1068336]
[31]
Zhang H, Wang P, Xue Y, Liu L, Li Z, Liu Y. Allicin ameliorates cognitive impairment in APP/PS1 mice via Suppressing oxidative stress by Blocking JNK Signaling Pathways. Tissue Cell 2018; 50: 89-95.
[http://dx.doi.org/10.1016/j.tice.2017.11.002] [PMID: 29429523]
[32]
Xiang Q. Allicin attenuates tunicamycin-induced cognitive deficits in rats via its synaptic plasticity regulatory activity. Iran J Basic Med Sci 2017; 20(6): 676-82.
[33]
Hao Z, Hai P, Yue W. Effect of allicin on the expression of tau protein in transgenic mice brain with Alzheimer’s disease. Nat Prod Res Dev 2016; 28(5): 685.
[34]
Kumar S. Dual inhibition of acetylcholinesterase and butyrylcholinesterase enzymes by allicin. Indian J Pharmacol 2015; 47(4): 444.
[http://dx.doi.org/10.4103/0253-7613.161274]
[35]
Thorajak P, Pannangrong W, Welbat JU, Chaijaroonkhanarak W, Sripanidkulchai K, Sripanidkulchai B. Effects of aged garlic extract on cholinergic, glutamatergic and gabaergic systems with regard to cognitive impairment in aβ-induced rats. Nutrients 2017; 9(7): 686.
[http://dx.doi.org/10.3390/nu9070686] [PMID: 28671572]
[36]
Zhu YF, Li XH, Yuan ZP, et al. Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway. Eur J Pharmacol 2015; 762(1): 239-46.
[http://dx.doi.org/10.1016/j.ejphar.2015.06.002] [PMID: 26049013]
[37]
Ray B, Chauhan NB, Lahiri DK. Oxidative insults to neurons and synapse are prevented by aged garlic extract and S-allyl-l-cysteine treatment in the neuronal culture and APP-Tg mouse model. J Neurochem 2011; 117(3): 388-402.
[http://dx.doi.org/10.1111/j.1471-4159.2010.07145.x] [PMID: 21166677]
[38]
Li X-H, Li C-Y, Xiang Z-G, Zhong F, Chen Z-Y, Lu J-M. Allicin can reduce neuronal death and ameliorate the spatial memory impairment in Alzheimers disease models. Neurosci J 2010; 15(4)
[39]
Dairam A, Fogel R, Daya S, Limson JL. Antioxidant and iron-binding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate. J Agric Food Chem 2008; 56(9): 3350-6.
[http://dx.doi.org/10.1021/jf0734931] [PMID: 18422331]
[40]
Gupta VB, Rao KSJ. Anti-amyloidogenic activity of S-allyl-l-cysteine and its activity to destabilize Alzheimer’s β-amyloid fibrils in vitro. Neurosci Lett 2007; 429(2-3): 75-80.
[http://dx.doi.org/10.1016/j.neulet.2007.09.042] [PMID: 18023978]
[41]
Chauhan NB. Effect of aged garlic extract on APP processing and tau phosphorylation in Alzheimer’s transgenic model Tg2576. J Ethnopharmacol 2006; 108(3): 385-94.
[http://dx.doi.org/10.1016/j.jep.2006.05.030] [PMID: 16842945]
[42]
Peng Q, Buz’Zard AR, Lau BHS. Neuroprotective effect of garlic compounds in amyloid-beta peptide-induced apoptosis in vitro. Med Sci Monit 2002; 8(8): BR328-37.
[PMID: 12165737]
[43]
Iadecola C, Gottesman RF. Neurovascular and cognitive dysfunction in hypertension: Epidemiology, pathobiology and treatment. Circ Res 2019; 124(7): 1025.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.313260]
[44]
Gottesman RF, Schneider ALC, Albert M, et al. Midlife hypertension and 20-year cognitive change: The atherosclerosis risk in communities neurocognitive study. JAMA Neurol 2014; 71(10): 1218-27.
[http://dx.doi.org/10.1001/jamaneurol.2014.1646] [PMID: 25090106]
[45]
Freitag MH, Peila R, Masaki K, et al. Midlife pulse pressure and incidence of dementia: The honolulu-asia aging study. Stroke 2006; 37(1): 33-7.
[http://dx.doi.org/10.1161/01.STR.0000196941.58869.2d] [PMID: 16339468]
[46]
Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ. The association between midlife blood pressure levels and late-life cognitive function. The honolulu-asia aging study. JAMA 1995; 274(23): 1846-51.
[http://dx.doi.org/10.1001/jama.1995.03530230032026] [PMID: 7500533]
[47]
Kaess BM, Rong J, Larson MG, et al. Aortic stiffness, blood pressure progression, and incident hypertension. JAMA 2012; 308(9): 875-81.
[http://dx.doi.org/10.1001/2012.jama.10503] [PMID: 22948697]
[48]
Capone C, Faraco G, Peterson JR, et al. Central cardiovascular circuits contribute to the neurovascular dysfunction in angiotensin II hypertension. J Neurosci 2012; 32(14): 4878-86.
[http://dx.doi.org/10.1523/JNEUROSCI.6262-11.2012] [PMID: 22492044]
[49]
Chen CY, Tsai TY, Chen BH. Effects of black garlic extract and nanoemulsion on the deoxy corticosterone acetate-salt induced hypertension and its associated mild cognitive impairment in rats. Antioxidants 2021; 10(10): 1611.
[http://dx.doi.org/10.3390/antiox10101611]
[50]
Al-Qattan KK, Thomson M, Jayasree D, Ali M. Garlic attenuates plasma and kidney ACE-1 and AngII modulations in early streptozotocin-induced diabetic rats: Renal clearance and blood pressure implications. Evid Based Complement Alternat Med 2016; 2016
[51]
Bonaz B, Bazin T, Pellissier S. The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front Neurosci 2018; 12(FEB): 49.
[http://dx.doi.org/10.3389/fnins.2018.00049] [PMID: 29467611]
[52]
Wang HX, Wang YP. Gut microbiota-brain axis. Chin Med J (Engl) 2016; 129(19): 2373-80.
[http://dx.doi.org/10.4103/0366-6999.190667] [PMID: 27647198]
[53]
Dinan TG, Cryan JF. The microbiome-gut-brain axis in health and disease. Gastroenterol Clin North Am 2017; 46(1): 77-89.
[http://dx.doi.org/10.1016/j.gtc.2016.09.007] [PMID: 28164854]
[54]
Galland L. The gut microbiome and the brain. J Med Food 2014; 17(12): 1261.
[55]
Alam R, Abdolmaleky HM, Zhou JR. Microbiome, inflammation, epigenetic alterations, and mental diseases. Am J Med Genet B Neuropsychiatr Genet 2017; 174(6): 651-60.
[http://dx.doi.org/10.1002/ajmg.b.32567] [PMID: 28691768]
[56]
Roubaud-Baudron C, Krolak-Salmon P, Quadrio I, Mégraud F, Salles N. Impact of chronic Helicobacter pylori infection on Alzheimer’s disease: Preliminary results. Neurobiol Aging 2012; 33(5): 1009.e11.
[http://dx.doi.org/10.1016/j.neurobiolaging.2011.10.021] [PMID: 22133280]
[57]
Angelucci F, Cechova K, Amlerova J, Hort J. Antibiotics, gut microbiota, and Alzheimer’s disease. J Neuroinflammation 2019; 16(1): 108.
[http://dx.doi.org/10.1186/s12974-019-1494-4] [PMID: 31118068]
[58]
Sunu P, Sunarti D, Mahfudz LD, Yunianto VD. Prebiotic activity of garlic (Allium sativum) extract on Lactobacillus acidophilus. Vet World 2019; 12(12): 2046-51.
[http://dx.doi.org/10.14202/vetworld.2019.2046-2051] [PMID: 32095058]
[59]
Lu X, Li N, Zhao R, Zhao M, Cui X, Xu Y, et al. In vitro prebiotic properties of garlic polysaccharides and its oligosaccharide mixtures obtained by acid hydrolysis. Front Nutr 2021; 8
[http://dx.doi.org/10.3389/fnut.2021.798450]
[60]
Bi J, Wang W, Du J, Chen K, Cheng K. Structure-activity relationship study and biological evaluation of SAC-Garlic acid conjugates as novel anti-inflammatory agents. Eur J Med Chem 2019; 179: 233-45.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.059] [PMID: 31255924]
[61]
Kim JM, Chang HJ, Kim WK, Chang N, Chun HS. Structure-activity relationship of neuroprotective and reactive oxygen species scavenging activities for allium organosulfur compounds. J Agric Food Chem 2006; 54(18): 6547-53.
[http://dx.doi.org/10.1021/jf060412c] [PMID: 16939308]

Rights & Permissions Print Cite
Article Metrics
30
2
Wayfinder Image
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy