Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Review Article

A Review of Eugenol-based Nanomedicine: Recent Advancements

Author(s): Mohammed A. Jahangir, Mohamad Taleuzzaman*, Sarwar Beg, Surajpal Verma, Sadaf J. Gilani and Perwaiz Alam

Volume 17, Issue 3, 2021

Published on: 25 May, 2020

Page: [214 - 219] Pages: 6

DOI: 10.2174/1573407216999200525145633

Price: $65

Abstract

Eugenol is a bioactive compound commonly found in many herbal plants. The different reported sources of eugenol are clove, cinnamon, holy basil, and pepper. Several therapeutic activities of eugenol like antioxidant, antimicrobial, anesthetic, anti-inflammatory, anti-carcinogenic, neuroprotective agent, anti-diabetic and anti-cancer activities have been reported. However, due to limited aqueous solubility, it has poor bioavailability. Its therapeutic potential can be enhanced by developing eugenol nano-formulations like liposome, nanoparticles, microemulsions and micelles. This article extensively reviews the chemical and pharmacological properties of eugenol and its nano-formulations along with their biological activities.

Keywords: Eugenol, nano formulation, microemulsions, micelles, pharmacological properties, pharmacokinetics.

Graphical Abstract

[1]
National Center for Biotechnology Information. PubChem Database., Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Eugenol [Accessed on 30th Sept 2019].
[2]
Barnes, J.; Anderson, L.; Phillipson, D. Herbal Medicine, 3rd ed.; Pharmaceutical Press: London, 2007.
[3]
Oyedemi, S.O.; Okoh, A.I.; Mabinya, L.V.; Pirochenva, G.; Afolayan, A.J. The Proposed mechanism of bactericidal action of eugenol, α-terpineol and terpinene against Listeria monocytogenes, Streptococcus pyogenes, Proteus vulgaris and Escherichia coli. Afr. J. Biotechnol., 2009, 8, 1280-1286.
[4]
Barceloux, D.G. Medical Toxicology of Natural Substances: Foods, Fungi, Medicinal Herbs, Plants and Venomous Animals; Wiley: Hoboken, New Jersey, 2008.
[http://dx.doi.org/10.1002/9780470330319]
[5]
Raja, M.R.C.; Srinivasan, V.; Selvaraj, S.; Mahapatra, S.K. Versatile and synergistic potential of eugenol: A review. Pharm. Anal. Acta, 2015, 6(5), 1-6.
[6]
Yadav, M.K.; Chae, S.W. Eugenol: A phyto-compound effective against methicillin resistant and methicillin-sensitive Staphylococcus aureus clinical strain biofilms. PLoS One, 2015, 17, 10 3.
[7]
Amin, S.; Khan, H. Revival of natural products: Utilization of modern technologies. Curr. Bioact. Compd., 2016, 1(12), 103-106.
[http://dx.doi.org/10.2174/1573407212666160314195845]
[8]
Chapter 6-Clove Oil (Eugenol). Available from: https://www.marinwater.org/Document Center/View/253
[9]
Khalil, A.A.; Rahman, U.; Khan, M.R.; Sahar, A.; Mehmood, T.; Khan, M. Essential oil eugenol: Sources, extraction techniques and nutraceutical perspectives. RSC Adv., 2017, 7, 32669.
[http://dx.doi.org/10.1039/C7RA04803C]
[10]
Zardo, D.M.; Alvarez, L.V.; Los, F.G.; Ito, V.C.; Travalini, A.P.; Cardoso, T.; Wojeicchoski, J.P.; Alberti, A.; Zielinski, A.A.; Esmerino, L.; Nogueira, A. In vitro assessment of the antibacterial and antioxidant properties of essential oils. Curr. Bioact. Compd., 2019, 15(5), 592-599.
[http://dx.doi.org/10.2174/1573407214666180720123150]
[11]
Rehman, S.; Khan, H. Advances in antioxidant potential of natural alkaloids. Curr. Bioact. Compd., 2017, 13(2), 101-108.
[http://dx.doi.org/10.2174/1573407212666160614075157]
[12]
Bouzid, W.; Yahia, M.; Benkiki, N.; Hachemi, M.; Meziti, A.; Haba, H. Antioxidant, anti-inflammatory, analgesic, and antipyretic effects of Urospermum dalechampii (L.) Scop. ex FW schmidt. Curr. Bioact. Compd., 2018, 14(3), 264-272.
[http://dx.doi.org/10.2174/1573407213666170221153848]
[13]
Prakash, P.; Gupta, N. Therapeutic uses of Ocimum sanctum Linn (Tulsi) with a note on eugenol and its pharmacological actions: A short review. Indian J. Physiol. Pharmacol., 2005, 49(2), 125-131.
[PMID: 16170979]
[14]
Kamatou, G.P.; Vermaak, I.; Viljoen, A.M. Eugenol-From the remote Maluku Islands to the international market place: A review of a remarkable and versatile molecule. Molecules, 2012, 17(6), 6953-6981.
[http://dx.doi.org/10.3390/molecules17066953] [PMID: 22728369]
[15]
Emerich, D.F.; Thanos, C.G. The pinpoint promise of nanoparticle-based drug delivery and molecular diagnosis. Biomol. Eng., 2006, 23(4), 171-184.
[http://dx.doi.org/10.1016/j.bioeng.2006.05.026] [PMID: 16843058]
[16]
Kohane, D.S. Microparticles and nanoparticles for drug delivery. Biotechnol. Bioeng., 2007, 96(2), 203-209.
[http://dx.doi.org/10.1002/bit.21301] [PMID: 17191251]
[17]
Fireman, S.; Toledano, O.; Neimann, K.; Loboda, N.; Dayan, N. A look at emerging delivery systems for topical drug products. Dermatol. Ther. (Heidelb.), 2011, 24(5), 477-488.
[http://dx.doi.org/10.1111/j.1529-8019.2012.01464.x] [PMID: 22353154]
[18]
Contri, R.V.; Frank, L.A.; Kaiser, M.; Pohlmann, A.R.; Guterres, S.S. The use of nanoencapsulation to decrease human skin irritation caused by capsaicinoids. Int. J. Nanomedicine, 2014, 9, 951-962.
[PMID: 24611011]
[19]
Siqueira, N.M.; Contri, R.V.; Paese, K.; Beck, R.C.; Pohlmann, A.R.; Guterres, S.S. Innovative sunscreen formulation based on benzophenone-3-loaded chitosan-coated polymeric nanocapsules. Skin Pharmacol. Physiol., 2011, 24(3), 166-174.
[http://dx.doi.org/10.1159/000323273] [PMID: 21273804]
[20]
Yogalakshmi, B.; Viswanathan, P.; Anuradha, C.V. Investigation of antioxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats. Toxicology, 2010, 268(3), 204-212.
[http://dx.doi.org/10.1016/j.tox.2009.12.018] [PMID: 20036707]
[21]
Irie, Y. Effects of eugenol on the central nervous system: its possible application to treatment of alzheimer’s disease, depression, and parkinson’s disease. Curr. Bioact. Compd., 2006, 2(1), 57-66.
[http://dx.doi.org/10.2174/1573407210602010057]
[22]
HuuDinha. Aci-quinone compounds from eugenoxyacetic acid and methyleugenol: Preparation and reaction. Curr. Org. Synth., 2016, 13(2), 300-305.
[23]
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]
[24]
Rauscher, F.M.; Sanders, R.A.; Watkins, J.B., III Effects of isoeugenol on oxidative stress pathways in normal and streptozotocin-induced diabetic rats. J. Biochem. Mol. Toxicol., 2001, 15(3), 159-164.
[http://dx.doi.org/10.1002/jbt.13] [PMID: 11424226]
[25]
Basch, E.; Gasparyan, A.; Giese, N.; Hashmi, S.; Miranda, M.; Sollars, D.; Seamon, E.; Tanguay-Colucci, S.; Ulbricht, C.; Varghese, M.; Vora, M.; Weissner, W. Clove (Eugenia aromatica) and clove oil (eugenol). Natural standard monograph (www.naturalstandard.com) copyright©. J. Diet Suppl., 2008, 5(2), 117-146.
[26]
Carrasco, H.A.; Espinoza, L.C.; Cardile, V.; Gallardo, C.; Cardona, W.; Lombardo, L.; Catalán, K.M.; Cuellar, M.F.; Russo, A. Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I). J. Braz. Chem. Soc., 2008, 19(3), 543-548.
[http://dx.doi.org/10.1590/S0103-50532008000300024]
[27]
Ito, M.; Murakami, K.; Yoshino, M. Antioxidant action of eugenol compounds: Role of metal ion in the inhibition of lipid peroxidation. Food Chem. Toxicol., 2005, 43(3), 461-466.
[http://dx.doi.org/10.1016/j.fct.2004.11.019] [PMID: 15680683]
[28]
Hamed, S.F.; Sadek, Z.; Edris, A. Antioxidant and antimicrobial activities of clove bud essential oil and eugenol nanoparticles in alcohol-free microemulsion. J. Oleo Sci., 2012, 61(11), 641-648.
[http://dx.doi.org/10.5650/jos.61.641] [PMID: 23138253]
[29]
Radünz, M.; da Trindade, M.L.M.; Camargo, T.M.; Radünz, A.L.; Borges, C.D.; Gandra, E.A.; Helbig, E. Antimicrobial and antioxidant activity of unencapsulated and encapsulated clove (Syzygium aromaticum, L.) essential oil. Food Chem., 2019, 276, 180-186.
[http://dx.doi.org/10.1016/j.foodchem.2018.09.173] [PMID: 30409582]
[30]
Benencia., F.; Courreges, M.C. In vitro and in vivo activity of eugenol on human herpes virus. Phytother. Res., 2000, 14, 495-500.
[http://dx.doi.org/10.1002/1099-1573(200011)14:7<495::AID-PTR650>3.0.CO;2-8] [PMID: 11054837]
[31]
Kim, S.S.; Oh, O.J. Eugenol suppresses cyclooxygenase-2 expression in lipo-polysaccharide stimulated mouse macrophage RAW264.7 cells. Life Sci., 2003, 6-73(3), 337-348.
[32]
Vidhya, N.; Devaraj, S.N. Induction of apoptosis by eugenol in human breast cancer cells. Indian J. Exp. Biol., 2011, 49(11), 871-878.
[PMID: 22126019]
[33]
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), 423-427.
[http://dx.doi.org/10.1248/bpb.30.423] [PMID: 17329831]
[34]
Garabadu, D.; Shah, A.; Ahmad, A.; Joshi, V.B.; Saxena, B.; Palit, G.; Krishnamurthy, S. 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), 145-155.
[http://dx.doi.org/10.3109/10253890.2010.521602] [PMID: 21034296]
[35]
Karthikesan, K.; Pari, L.; Menon, V.P. Protective effect of tetrahydrocurcumin and chlorogenic acid against streptozotocin–Nicotinamide generated oxidative stress induced diabetes. J. Funct. Foods, 2010, 2, 134-142.
[http://dx.doi.org/10.1016/j.jff.2010.04.001]
[36]
Singh, P.; Jayaramaiah, R.H.; Agawane, S.B.; Vannuruswamy, G.; Korwar, A.M.; Anand, A.; Dhaygude, V.S.; Shaikh, M.L.; Joshi, R.S.; Boppana, R.; Kulkarni, M.J.; Thulasiram, H.V.; Giri, A.P. Potential dual role of eugenol in inhibiting advanced glycation end products in diabetes: Proteomic and mechanistic insights. Sci. Rep., 2016, 6, 18798.
[http://dx.doi.org/10.1038/srep18798] [PMID: 26739611]
[37]
Venkadeswaran, K.; Muralidharan, A.R.; Annadurai, T.; Ruban, V.V.; Sundararajan, M.; Anandhi, R.; Thomas, P.A. Antihypercholesterolemic and antioxidative potential of an extract of the plant, Piper betle, and its active constituent, eugenol. Triton WR-1339-induced hypercholesterolemia in experimental rats; Evid. Based Complement. Altern. Med., 2014, 2014, 478973.
[38]
Jin, S.; Cho, K.H. Water extracts of cinnamon and clove exhibits potent inhibition of protein glycation and anti-atherosclerotic activity in vitro and in vivo hypolipidemic activity in zebrafish. Food Chem. Toxicol., 2011, 49(7), 1521-1529.
[http://dx.doi.org/10.1016/j.fct.2011.03.043] [PMID: 21443916]
[39]
Criddle, D.N.; Madeira, S.V.; Soares de Moura, R. Endothelium-dependent and -Independent vasodilator effects of eugenol in the rat mesenteric vascular bed. J. Pharm. Pharmacol., 2003, 55(3), 359-365.
[http://dx.doi.org/10.1211/002235702694] [PMID: 12724042]
[40]
Damiani, C.E.; Rossoni, L.V.; Vassallo, D.V. Vasorelaxant effects of eugenol on rat thoracic aorta. Vascul. Pharmacol., 2003, 40(1), 59-66.
[http://dx.doi.org/10.1016/S1537-1891(02)00311-7] [PMID: 12646411]
[41]
Thompson, D.; Eling, T. Mechanism of inhibition of prostaglandin H synthase by eugenol and other phenolic peroxidase substrates. Mol. Pharmacol., 1989, 36(5), 809-817.
[PMID: 2511429]
[42]
Han, X.; Parker, T.L. Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts. Pharm. Biol., 2017, 55(1), 1619-1622.
[http://dx.doi.org/10.1080/13880209.2017.1314513] [PMID: 28407719]
[43]
Dallmeier Zelger, K.R.; Zelger, J.L.; Carlini, E.A.; Carlini, A. New anticonvulsants derived from 4-allyl-2-methoxyphenol (Eugenol): Comparison with common antiepileptics in mice. Pharmacology, 1983, 27(1), 40-49.
[http://dx.doi.org/10.1159/000137828] [PMID: 6611647]
[44]
Guenette, S.A.; Beaudry, F.; Marier, J.F.; Vachon, P. Pharmacokinetics and anesthetic activity of eugenol in male Sprague-Dawley rats. J. Vet. Pharmacol. Ther., 2006, 29(4), 265-270.
[http://dx.doi.org/10.1111/j.1365-2885.2006.00740.x] [PMID: 16846463]
[45]
Schmidt, E.; Jirovetz, L.; Wlcek, K.; Buchbauer, G.; Gochev, V.; Girova, T.; Stoyanova, A.; Geissler, M. Antifungal activity of eugenol and various eugenol-containing essential oils against 38 clinical isolates of Candida albicans. J. Essent. Oil-Bear. Plants, 2007, 10(5), 421-429.
[http://dx.doi.org/10.1080/0972060X.2007.10643575]
[46]
Sebaaly, C.; Jraij, A.; Fessi, H.; Charcosset, C.; Greige-Gerges, H. Preparation and characterization of clove essential oil-loaded liposomes. Food Chem., 2015, 178, 52-62.
[http://dx.doi.org/10.1016/j.foodchem.2015.01.067] [PMID: 25704683]
[47]
Sebaaly, C.; Charcosset, C.; Stainmesse, S.; Fessi, H.; Greige-Gerges, H. Clove essential oil-in-cyclodextrin-in-liposomes in the aqueous and lyophilized states: From laboratory to large scale using a membrane contactor. Carbohydr. Polym., 2016, 138, 75-85.
[http://dx.doi.org/10.1016/j.carbpol.2015.11.053] [PMID: 26794740]
[48]
Ahmad, N.; Ahmad, R.; Alam, M.A.; Ahmad, F.J. Quantification and brain targeting of eugenol-loaded surface modified nanoparticles through intranasal route in the treatment of Cerebral ischemia. Drug Res. (Stuttg.), 2018, 68(10), 584-595.
[http://dx.doi.org/10.1055/a-0596-7288] [PMID: 29669380]
[49]
Shao, Y.; Wu, C.; Wu, T.; Li, Y.; Chen, S.; Yuan, C.; Hu, Y. Eugenol-chitosan nanoemulsions by ultrasound-mediated emulsification: Formulation, characterization and antimicrobial activity. Carbohydr. Polym., 2018, 193, 144-152.
[http://dx.doi.org/10.1016/j.carbpol.2018.03.101] [PMID: 29773366]
[50]
Al-Okbi, S.Y.; Mohamed, D.A.; Hamed, T.E.; Edris, A.E. Protective effect of clove oil and eugenol microemulsions on fatty liver and dyslipidemia as components of metabolic syndrome. J. Med. Food, 2014, 17(7), 764-771.
[http://dx.doi.org/10.1089/jmf.2013.0033] [PMID: 24611461]
[51]
Esmaeili, F.; Rajabnejhad, S.; Partoazar, A.R.; Mehr, S.E.; Faridi-Majidi, R.; Sahebgharani, M.; Syedmoradi, L.; Rajabnejhad, M.R.; Amani, A. Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system. Pharm. Dev. Technol., 2016, 21(7), 887-893.
[http://dx.doi.org/10.3109/10837450.2015.1078353] [PMID: 26365132]
[52]
Ghosh, V.; Mukherjee, A.; Chandrasekaran, N. Eugenol-loaded antimicrobial nanoemulsion preserves fruit juice against, microbial spoilage. Colloids Surf. B Biointerfaces, 2014, 114, 392-397.
[http://dx.doi.org/10.1016/j.colsurfb.2013.10.034] [PMID: 24252231]
[53]
Jadhav, B.K.; Khandelwal, K.R.; Ketkar, A.R.; Pisal, S.S. Formulation and evaluation of mucoadhesive tablets containing eugenol for the treatment of periodontal diseases. Drug Dev. Ind. Pharm., 2004, 30(2), 195-203.
[http://dx.doi.org/10.1081/DDC-120028715] [PMID: 15089054]
[54]
Garg, A.; Singh, S. Enhancement in antifungal activity of eugenol in immunosuppressed rats through lipid nanocarriers. Colloids Surf. B. Biointerfaces, 2011, 87(2), 280-288.
[http://dx.doi.org/10.1016/j.colsurfb.2011.05.030]
[55]
Garg, A.; Singh, S. Targeting of eugenol-loaded solid lipid nanoparticles to the epidermal layer of human skin. Nanomedicine (Lond.), 2014, 9(8), 1223-1238.
[http://dx.doi.org/10.2217/nnm.13.33] [PMID: 23987096]
[56]
Zhao, X.; Chen, D.; Gao, P.; Ding, P.; Li, K. Synthesis of ibuprofen eugenol ester and its microemulsion formulation for parenteral delivery. Chem. Pharm. Bull. (Tokyo), 2005, 53(10), 1246-1250.
[http://dx.doi.org/10.1248/cpb.53.1246] [PMID: 16204978]
[57]
Shen, Q.; Wang, Y.; Zhang, Y. Improvement of colchicine oral bioavailability by incorporating eugenol in the nanoemulsion as an oil excipient and enhancer. Int. J. Nanomedicine, 2011, 6, 1237-1243.
[http://dx.doi.org/10.2147/IJN.S20903] [PMID: 21753875]
[58]
da Silva Gündel, S.; Dos Reis, T.R.; Copetti, P.M.; Favarin, F.R.; Sagrillo, M.R.; da Silva, A.S.; Segat, J.C.; Baretta, D.; Ourique, A.F. Evaluation of cytotoxicity, genotoxicity and ecotoxicity of nanoemulsions containing Mancozeb and Eugenol. Ecotoxicol. Environ. Saf., 2019, 169, 207-215.
[http://dx.doi.org/10.1016/j.ecoenv.2018.11.023] [PMID: 30448703]
[59]
Gomes, C.; Moreira, R.G.; Castell-Perez, E. Poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped trans-cinnamaldehyde and eugenol for antimicrobial delivery applications. J. Food Sci., 2011, 76(2), N16-N24.
[http://dx.doi.org/10.1111/j.1750-3841.2010.01985.x] [PMID: 21535781]
[60]
Seo, E.J.; Min, S.G.; Choi, M.J. Release characteristics of freeze-dried eugenol encapsulated with beta-cyclodextrin by molecular inclusion method. J. Microencapsul., 2010, 27(6), 496-505.
[http://dx.doi.org/10.3109/02652041003681398] [PMID: 20214546]
[61]
Schecter, A.; Lucier, G.W.; Cunningham, M.L.; Abdo, K.M.; Blumenthal, G.; Silver, A.G.; Melnick, R.; Portier, C.; Barr, D.B.; Barr, J.R.; Stanfill, S.B.; Patterson, D.G., Jr; Needham, L.L.; Stopford, W.; Masten, S.; Mignogna, J.; Tung, K.C. Human consumption of methyleugenol and its elimination from serum. Environ. Health Perspect., 2004, 112(6), 678-680.
[http://dx.doi.org/10.1289/ehp.6766] [PMID: 15121510]
[62]
Smith, R.L.; Adams, T.B.; Doull, J.; Feron, V.J.; Goodman, J.I.; Marnett, L.J.; Portoghese, P.S.; Waddell, W.J.; Wagner, B.M.; Rogers, A.E.; Caldwell, J.; Sipes, I.G. Safety assessment of allylalkoxybenzene derivatives used as flavouring substances - Methyl eugenol and estragole. Food Chem. Toxicol., 2002, 40(7), 851-870.
[http://dx.doi.org/10.1016/S0278-6915(02)00012-1] [PMID: 12065208]
[63]
Thompson, D.C.; Constantin-Teodosiu, D.; Moldéus, P. Metabolism and cytotoxicity of eugenol in isolated rat hepatocytes. Chem. Biol. Interact., 1991, 77(2), 137-147.
[http://dx.doi.org/10.1016/0009-2797(91)90069-J] [PMID: 1991333]

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