Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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

Preclinical Evidence-based Review on Therapeutic Potential of Eugenol for the Treatment of Brain Disorders

Author(s): Ahsas Goyal*, Ashutosh Solanki and Aanchal Verma

Volume 23, Issue 5, 2023

Published on: 27 July, 2022

Page: [390 - 400] Pages: 11

DOI: 10.2174/1566524022666220525145521

Price: $65

Abstract

The increasing morbidness of brain disorders and conditions, such as anxiety, stress, depression, Alzheimer’s disease, Parkinson’s disease, and others, have become severe. Although researchers have spent a significant amount of time examining these diseases and providing many benefits, there are still limited drugs available to treat these disorders. Eugenol, a dietary component present in numerous plants and herbs, possesses various health benefits. In various preclinical studies, eugenol has provided significant protective effects against a variety of brain disorders. Thus, including eugenol in the diet can fight various diseases and ensure a healthy life. Considering the fruitful impact of this compound, this review focuses on the brain disorders in which eugenol was used, and summarizes the beneficial properties of eugenol and its role in treating various brain diseases.

Keywords: Eugenol, brain disorders, parkinson’s disease, Alzheimer’s disease, stress, analgesia, epilepsy, depression.

« Previous Next »
[1]
Zahiruddin S, Basist P, Parveen A, Parveen R, Khan W. Gaurav; Ahmad, S. Ashwagandha in brain disorders: A review of recent developments. J Ethnopharmacol 2020; 257: 112876.
[2]
Lima Giacobbo B, Doorduin J, Klein HC, Dierckx RAJO, Bromberg E, de Vries EFJ. Brain-derived neurotrophic factor in brain disorders: Focus on neuroinflammation. Mol Neurobiol 2019; 56(5): 3295-312.
[http://dx.doi.org/10.1007/s12035-018-1283-6] [PMID: 30117106]
[3]
Henriques JF, Serra D, Dinis TCP, Almeida LM. The anti-neuroinflammatory role of anthocyanins and their metabolites for the prevention and treatment of brain disorders. Int J Mol Sci 2020; 21(22): 1-31.
[http://dx.doi.org/10.3390/ijms21228653] [PMID: 33212797]
[4]
Singh V, Panwar R. In vivo antioxidative and neuroprotective effect of 4-Allyl-2-methoxyphenol against chlorpyrifos-induced neurotoxicity in rat brain. Mol Cell Biochem 2014; 388(1-2): 61-74.
[http://dx.doi.org/10.1007/s11010-013-1899-9] [PMID: 24292926]
[5]
Barboza JN, da Silva Maia Bezerra Filho C, Silva RO, Medeiros JVR, de Sousa DP. An overview on the anti-inflammatory potential and antioxidant profile of eugenol. Oxid Med Cell Longev 2018; 2018: 3957262.
[http://dx.doi.org/10.1155/2018/3957262]
[6]
Zhang P, Zhang E, Xiao M, Chen C, Xu W. Study of anti-inflammatory activities of α-D-glucosylated eugenol. Arch Pharm Res 2013; 36(1): 109-15.
[http://dx.doi.org/10.1007/s12272-013-0003-z] [PMID: 23325490]
[7]
Fujisawa S, Atsumi T, Kadoma Y, Sakagami H. Antioxidant and prooxidant action of eugenol-related compounds and their cytotoxicity. Toxicology 2002; 177(1): 39-54.
[http://dx.doi.org/10.1016/S0300-483X(02)00194-4] [PMID: 12126794]
[8]
Hemaiswarya S, Doble M. Synergistic interaction of eugenol with antibiotics against gram negative bacteria. Phytomedicine 2009; 16(11): 997-1005.
[http://dx.doi.org/10.1016/j.phymed.2009.04.006] [PMID: 19540744]
[9]
Kim HM, Lee EH, Kim CY, et al. Antianaphylactic properties of eugenol. Pharmacol Res 1997; 36(6): 475-80.
[http://dx.doi.org/10.1006/phrs.1997.0256] [PMID: 9508673]
[10]
Baskaran Y, Periyasamy V, Venkatraman AC. Corrigendum to “Investigation of antioxidant, anti-inflammatory and dnaprotective properties of eugenol in thioacetamide-induced liver injury in rats” Toxicology 268(3): 204-12.
[http://dx.doi.org/10.1016/j.tox.2009.12.018]
[11]
Moreira Vasconcelos CF, da Cunha Ferreira NM, Hardy Lima Pontes N, et al. Eugenol and its association with levodopa in 6-hydroxydopamine-induced hemiparkinsonian rats: Behavioural and neurochemical alterations. Basic Clin Pharmacol Toxicol 2020; 127(4): 287-302.
[http://dx.doi.org/10.1111/bcpt.13425] [PMID: 32353201]
[12]
Rodrigues TG, Fernandes A Jr, Sousa JPB, Bastos JK, Sforcin JM. In vitro and in vivo effects of clove on pro-inflammatory cytokines production by macrophages. Nat Prod Res 2009; 23(4): 319-26.
[http://dx.doi.org/10.1080/14786410802242679] [PMID: 19296372]
[13]
Hui Q, Ammeter E, Liu S, et al. Eugenol attenuates inflammatory response and enhances barrier function during lipopolysaccharide-induced inflammation in the porcine intestinal epithelial cells. J Anim Sci 2020; 98(8): 98.
[http://dx.doi.org/10.1093/jas/skaa245] [PMID: 32735667]
[14]
Pinto E, Vale-Silva L, Cavaleiro C, Salgueiro L. Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species. J Med Microbiol 2009; 58(Pt 11): 1454-62.
[http://dx.doi.org/10.1099/jmm.0.010538-0] [PMID: 19589904]
[15]
Yagura S, Onimaru H, Kanzaki K, Izumizaki M. Inhibitory effects of eugenol on putative nociceptive response in spinal cord preparation isolated from neonatal rats. Exp Brain Res 2018; 236(6): 1767-74.
[http://dx.doi.org/10.1007/s00221-018-5254-y] [PMID: 29654351]
[16]
Barbas LAL, Torres MF, da Costa BMPA, et al. Eugenol induces body immobilization yet evoking an increased neuronal excitability in fish during short-term baths. Aquat Toxicol 2021; 231: 105734.
[http://dx.doi.org/10.1016/j.aquatox.2020.105734] [PMID: 33385846]
[17]
Marchese A, Barbieri R, Coppo E, et al. Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint. Crit Rev Microbiol 2017; 43(6): 668-89.
[http://dx.doi.org/10.1080/1040841X.2017.1295225] [PMID: 28346030]
[18]
Ashrafudoulla M, Mizan MFR, Ha AJ. won; Park SH, Ha S do. Antibacterial and antibiofilm mechanism of eugenol against antibiotic resistance vibrio parahaemolyticus. Food Microbiol 2020; 91: 103500.
[19]
Pessoa LM, Morais SM, Bevilaqua CML, Luciano JHS. Anthelmintic activity of essential oil of Ocimum gratissimum Linn. and eugenol against Haemonchus contortus. Vet Parasitol 2002; 109(1-2): 59-63.
[http://dx.doi.org/10.1016/S0304-4017(02)00253-4] [PMID: 12383625]
[20]
Gülçin İ. Antioxidant activity of eugenol: A structure-activity relationship study. J Med Food 2011; 14(9): 975-85.
[http://dx.doi.org/10.1089/jmf.2010.0197] [PMID: 21554120]
[21]
Magalhães CB, Casquilho NV, Machado MN, et al. The anti-inflammatory and anti-oxidative actions of eugenol improve lipopolysaccharide-induced lung injury. Respir Physiol Neurobiol 2019; 259: 30-6.
[http://dx.doi.org/10.1016/j.resp.2018.07.001] [PMID: 29997055]
[22]
Prasad SN. Evidence of acrylamide induced oxidative stress and neurotoxicity in Drosophila melanogaster - its amelioration with spice active enrichment: Relevance to neuropathy. Neurotoxicology 2012; 33(5): 1254-64.
[http://dx.doi.org/10.1016/j.neuro.2012.07.006] [PMID: 22841601]
[23]
Nikbin S, Derakhshideh A, Kanozi F, et al. Combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by chlorpyrifos. Mol Biol Rep 2020; 47(8): 5985-96.
[http://dx.doi.org/10.1007/s11033-020-05672-4] [PMID: 32780254]
[24]
Ahmad N, Ahmad R, Alam MA, Ahmad FJ. Quantification and brain targeting of eugenol-loaded surface modified nanoparticles through intranasal route in the treatment of cerebral ischemia. Drug Res 2018; 68(10): 584-95.
[http://dx.doi.org/10.1055/a-0596-7288] [PMID: 29669380]
[25]
Said MM. The protective effect of eugenol against gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Fundam Clin Pharmacol 2011; 25(6): 708-16.
[http://dx.doi.org/10.1111/j.1472-8206.2010.00900.x] [PMID: 21105912]
[26]
Manikandan P, Vinothini G, Vidya Priyadarsini R, Prathiba D, Nagini S. Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNG. Invest New Drugs 2011; 29(1): 110-7.
[http://dx.doi.org/10.1007/s10637-009-9345-2] [PMID: 19851710]
[27]
Júnior PLDS, Câmara DAD, Costa AS, et al. Apoptotic effect of eugenol envolves G2/M phase abrogation accompanied by mitochondrial damage and clastogenic effect on cancer cell in vitro. Phytomedicine 2016; 23(7): 725-35.
[http://dx.doi.org/10.1016/j.phymed.2016.03.014] [PMID: 27235711]
[28]
Nam H, Kim MM. Eugenol with antioxidant activity inhibits MMP-9 related to metastasis in human fibrosarcoma cells. Food Chem Toxicol 2013; 55: 106-12.
[http://dx.doi.org/10.1016/j.fct.2012.12.050] [PMID: 23313798]
[29]
Wie MB, Won MH, Lee KH, et al. Eugenol protects neuronal cells from excitotoxic and oxidative injury in primary cortical cultures. Neurosci Lett 1997; 225(2): 93-6.
[http://dx.doi.org/10.1016/S0304-3940(97)00195-X] [PMID: 9147382]
[30]
Kabuto H, Tada M, Kohno M. Eugenol [2-methoxy-4-(2-propenyl)phenol] prevents 6-hydroxydopamine-induced dopamine depression and lipid peroxidation inductivity in mouse striatum. Biol Pharm Bull 2007; 30(3): 423-7.
[http://dx.doi.org/10.1248/bpb.30.423] [PMID: 17329831]
[31]
Pontes KAO, Silva LS, Santos EC, et al. Eugenol disrupts plasmodium falciparum intracellular development during the erythrocytic cycle and protects against cerebral malaria. Biochimica et Biophysica Acta - General Subjects 2021; 1865(3): 129813.
[32]
Adefegha SA, Okeke BM, Oboh G. Antioxidant properties of eugenol, butylated hydroxylanisole, and butylated hydroxyl toluene with key biomolecules relevant to Alzheimer’s diseases-In vitro. J Food Biochem 2021; 45(3): e13276.
[http://dx.doi.org/10.1111/jfbc.13276] [PMID: 32458455]
[33]
National Center for Biotechnology Information. PubChem Compound Summary for CID 3314, Eugenol. 2022. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/ Eugenol
[34]
Garabadu D, Sharma M. Eugenol attenuates scopolamine-induced hippocampal cholinergic, glutamatergic, and mitochondrial toxicity in experimental rats. Neurotox Res 2019; 35(4): 848-59.
[http://dx.doi.org/10.1007/s12640-019-0008-6] [PMID: 30737653]
[35]
Jayasingh Chellammal HS, Veerachamy A, Ramachandran D, Gummadi SB, Manan MM, Yellu NR. Neuroprotective effects of 1‘δ-1′-acetoxyeugenol acetate on Aβ(25-35) induced cognitive dysfunction in mice. Biomed Pharmacother 2019; 109: 1454-61.
[http://dx.doi.org/10.1016/j.biopha.2018.10.189] [PMID: 30551397]
[36]
Liu Z, Niu W, Yang X, Wang Y. Effects of combined acupuncture and eugenol on learning-memory ability and antioxidation system of hippocampus in Alzheimer disease rats via olfactory system stimulation. J Tradit Chin Med 2013; 33(3): 399-402.
[http://dx.doi.org/10.1016/S0254-6272(13)60186-7] [PMID: 24024340]
[37]
Said MM, Rabo MMA. Neuroprotective effects of eugenol against aluminiuminduced toxicity in the rat brain. Arh Hig Rada Toksikol 2017; 68(1): 27-37.
[http://dx.doi.org/10.1515/aiht-2017-68-2878] [PMID: 28365674]
[38]
Jeong KH, Lee DS, Kim SR. Effects of eugenol on granule cell dispersion in a mouse model of temporal lobe epilepsy. Epilepsy Res 2015; 115: 73-6.
[http://dx.doi.org/10.1016/j.eplepsyres.2015.06.001] [PMID: 26220380]
[39]
Joushi S, Salmani ME. Effect of eugenol on lithium-pilocarpine model of epilepsy: Behavioral, histological, and molecular changes. Iran J Basic Med Sci 2017; 20(7): 745-52.
[PMID: 28852438]
[40]
Müller M, Pape HC, Speckmann EJ, Gorji A. Effect of eugenol on spreading depression and epileptiform discharges in rat neocortical and hippocampal tissues. Neuroscience 2006; 140(2): 743-51.
[http://dx.doi.org/10.1016/j.neuroscience.2006.02.036] [PMID: 16563641]
[41]
Gao X feng, Liu Q, Qing H, et al. Development of eugenol-loaded submicron emulsion and its antiepileptic effect through regulating the oxidative stress. Int J Pharm 2020; 587.
[42]
Huang CW, Chow JC, Tsai JJ, Wu SN. Characterizing the effects of eugenol on neuronal ionic currents and hyperexcitability. Psychopharmacology 2012; 221(4): 575-87.
[http://dx.doi.org/10.1007/s00213-011-2603-y] [PMID: 22160139]
[43]
Lionnet L, Beaudry F, Vachon P. Intrathecal eugenol administration alleviates neuropathic pain in male Sprague-Dawley rats. Phytother Res 2010; 24(11): 1645-53.
[http://dx.doi.org/10.1002/ptr.3174] [PMID: 21031622]
[44]
Cho JS, Kim TH, Lim JM, Song JH. Effects of eugenol on Na+ currents in rat dorsal root ganglion neurons. Brain Res 2008; 1243: 53-62.
[http://dx.doi.org/10.1016/j.brainres.2008.09.030] [PMID: 18824159]
[45]
Paula-Freire LIG, Molska GR, Andersen ML, Carlini ELDA. Ocimum gratissimum essential oil and its isolated compounds (eugenol and myrcene) reduce neuropathic pain in mice. Planta Med 2016; 82(3): 211-6.
[PMID: 26584457]
[46]
Yano S, Suzuki Y, Yuzurihara M, et al. Antinociceptive effect of methyleugenol on formalin-induced hyperalgesia in mice. Eur J Pharmacol 2006; 553(1-3): 99-103.
[http://dx.doi.org/10.1016/j.ejphar.2006.09.020] [PMID: 17049512]
[47]
Bahramsoltani R, Farzaei MH, Farahani MS, Rahimi R. Phytochemical constituents as future antidepressants: A comprehensive review. Rev Neurosci 2015; 26(6): 699-719.
[http://dx.doi.org/10.1515/revneuro-2015-0009] [PMID: 26146123]
[48]
do Amaral JF, Silva MIG, de Aquino Neto MR, et al. Antidepressant-like effect of bis-eugenol in the mice forced swimming test: Evidence for the involvement of the monoaminergic system. Fundam Clin Pharmacol 2013; 27(5): 471-82.
[http://dx.doi.org/10.1111/j.1472-8206.2012.01058.x] [PMID: 22827775]
[49]
Irie Y, Itokazu N, Anjiki N, Ishige A, Watanabe K, Keung WM. Eugenol exhibits antidepressant-like activity in mice and induces expression of metallothionein-III in the hippocampus. Brain Res 2004; 1011(2): 243-6.
[http://dx.doi.org/10.1016/j.brainres.2004.03.040] [PMID: 15157811]
[50]
Tao G, Irie Y, Li DJ, Keung WM. Eugenol and its structural analogs inhibit monoamine oxidase A and exhibit antidepressant-like activity. Bioorg Med Chem 2005; 13(15): 4777-88.
[http://dx.doi.org/10.1016/j.bmc.2005.04.081] [PMID: 15936201]
[51]
Norte MCB, Cosentino RM, Lazarini CA. Effects of methyl-eugenol administration on behavioral models related to depression and anxiety, in rats. Phytomedicine 2005; 12(4): 294-8.
[http://dx.doi.org/10.1016/j.phymed.2003.12.007] [PMID: 15898707]
[52]
Dhiman P, Malik N, Khatkar A. Lead optimization for promising monoamine oxidase inhibitor from eugenol for the treatment of neurological disorder: Synthesis and in silico based study. BMC Chem 2019; 13(1): 38.
[http://dx.doi.org/10.1186/s13065-019-0552-4] [PMID: 31384786]
[53]
Garabadu D, Shah A, Ahmad A, et al. Eugenol as an anti-stress agent: Modulation of hypothalamic-pituitary-adrenal axis and brain monoaminergic systems in a rat model of stress. Stress 2011; 14(2): 145-55.
[http://dx.doi.org/10.3109/10253890.2010.521602] [PMID: 21034296]
[54]
Wang X, Chen Y, Wang Q, et al. Support for natural small-molecule phenols as anxiolytics. Molecules 2017; 22(12): 22.
[http://dx.doi.org/10.3390/molecules22122138] [PMID: 29210995]
[55]
Ma L, Mu Y, Zhang Z, Sun Q. Eugenol promotes functional recovery and alleviates inflammation, oxidative stress, and neural apoptosis in a rat model of spinal cord injury. Restor Neurol Neurosci 2018; 36(5): 659-68.
[http://dx.doi.org/10.3233/RNN-180826] [PMID: 30040768]
[56]
Robin O, Alaoui-Ismaïli O, Dittmar A, Vernet-Maury E. Basic emotions evoked by eugenol odor differ according to the dental experience. A neurovegetative analysis. Chem Senses 1999; 24(3): 327-35.
[http://dx.doi.org/10.1093/chemse/24.3.327] [PMID: 10400451]
[57]
Prasad SN. Neuroprotective efficacy of eugenol and isoeugenol in acrylamide-induced neuropathy in rats: Behavioral and biochemical evidence. Neurochem Res 2013; 38(2): 330-45.
[http://dx.doi.org/10.1007/s11064-012-0924-9] [PMID: 23161090]
[58]
Prasad SN, Bharath MS. Neurorestorative effects of eugenol, a spice bioactive: Evidence in cell model and its efficacy as an intervention molecule to abrogate brain oxidative dysfunctions in the streptozotocin diabetic rat. Neurochem Int 2016; 95: 24-36.
[http://dx.doi.org/10.1016/j.neuint.2015.10.012] [PMID: 26519099]
[59]
Guo KF, Dai M, Liu YM, et al. Acute Administration of methyleugenol impairs hippocampus-dependent contextual fear memory and increases anxiety-like behavior in mice. J Agric Food Chem 2020; 68(28): 7490-7.
[http://dx.doi.org/10.1021/acs.jafc.0c01863] [PMID: 32551566]
[60]
Lane BW, Ellenhorn MJ, Hulbert TV, McCarron M. Clove oil ingestion in an infant. Hum Exp Toxicol 1991; 10(4): 291-4.
[http://dx.doi.org/10.1177/096032719101000410] [PMID: 1679654]
[61]
Kabuto H, Yamanushi TT. Effects of zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone] and eugenol [2-methoxy-4-(2-propenyl)phenol] on the pathological progress in the 6-hydroxydopamine-induced Parkinson’s disease mouse model. Neurochem Res 2011; 36(12): 2244-9.
[http://dx.doi.org/10.1007/s11064-011-0548-5] [PMID: 21769642]

Rights & Permissions Print Cite
Article Metrics
7
© 2024 Bentham Science Publishers | Privacy Policy