VERSATILE AND SYNERGISTIC POTENTIAL OF EUGENOL
Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) is the phenolic component of essential oil and the main constituent of Eugenia caryophyllata, Ocimmum gratissimum and several others medicinal plant. In view of its non-mutagenic and non-carcinogenic properties, eugenol is generally regarded as safe by the Food and Agricultural Organization of the United Nations. Eugenol has been recently shown to be effective for antimicrobials and treatment of different life threatening diseases including sepsis, leishmaniasis, and cancer. However, overall, activity of eugenol is not discussed elsewhere. In this review, we discuss the current understanding of the mechanisms involved the antioxidant, antimicrobial, anticancer and anti-inflammatory potential of eugenol.
2. World Health Organization. Evaluation of Certain Food Additives and Contaminants; Twenty-sixth report of the Joint FAO/WHO Expert Committee on Food Additives, WHO Technical Report Series, No. 683; Geneva, Switzerland; 1982.
3. Kar Mahapatra S, Chakraborty SP, Majumdar S, Bag BG, Roy S. Eugenol protects nicotine-induced superoxide mediated oxidative damage in murine peritoneal macrophages in vitro. Eur J Pharmacol 2009;623:132-40.
4. Yogalakshmi B, Viswanathan P, Anuradha CV. Investigation of anti-oxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats. Toxicology 2010;268:204â€“12.
5. Kar Mahapatra S, Bhattacharjee S, Chakraborty SP, Majumdar S, Roy S. Alteration of immune functions and Th1/Th2 cytokine balance in nicotine-induced murine macrophages: immunomodulatory role of eugenol and N-acetylcysteine. Int Immunopharmacol 2011;11:485-95.
6. Kar Mahapatra S, Roy S. Phytopharmacological approach of free radical scavenging and anti-oxidative potential of eugenol and Ocimum gratissimum Linn. Asian Pac J Trop Med 2014;7S1:S391-7.
7. Harborne JB, Baxter H. Phytochemical Dictionary; Taylor and Francis: London, UK; 1993.
8. WHO; Food Additive Series 17: Eugenol; 1980.
9. Thompson DC, Constantin-Teodosiu D, Moldeus P. Metabolism and cytotoxicity of eugenol in isolated rat hepatocytes. Chem Biol Interact 1991;77:137-47.
10. Bedoukian PZ. Perfumery and Flavouring Synthetics. 3rd ed.; Allured Publishing Corporation: Carol Stream, IL, USA; 1986.
11. Zheng GQ, Kenney PM, Lam LKT. Sesquiterpenes from clove (Eugenia caryophyllata). J Nat Prod 1992;55:999â€“1003.
12. USDA. Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Eugenol. Washington, DC: US Dept Agric, Agric Res Service; 2012. Available from: URL: http://www.ars-grin.gov/duke/. [Last accessed on 20 Apr]
13. Sudarma IM, Ulfa M, Sarkono. Chemical transformation of eugenol isolated from clove oil to 4-allyl-2-methoxy-6-sulfonicphenol and 4-allyl-2-methoxy-6-aminophenol. Indones J Chem 2009;9:267â€“70.
14. Tominaga H, Kobayashi Y, Goto T, Kasemura K, Nomura M. DPPH radical scavenging effect of several phenylpropanoid compounds and their glycoside derivatives. Yakugaku Zasshi 2005;125:371-5.
15. Slamenova D, Horvathova E, Wsolova L, Sramkova M, Navarova J. Investigation of anti-oxidative, cytotoxic, DNA-damaging and DNA-protective effects of plant volatiles eugenol and borneol in human-derived HepG2, Caco-2 and VH10 cell lines. Mutat Res 2009;677:46â€“52.
16. Mahboub R, Memmou F. Antioxidant activity and kinetics studies of eugenol and 6-bromoeugenol. Nat Prod Res 2014;17:1-6.
17. Chogo JB, Crank G. Chemical composition and biological activity of the Tanzanian plant Ocimum suave. J Nat Prod 1981;42:308â€“11.
18. Ito M, Murakami K, Yoshino M. Anti-oxidant action of eugenol compounds: role of metal ion in the inhibition of lipid peroxidation. Food Chem Toxicol 2005;43:461â€“6.
19. Rao M, Kumar MM, Rao MA. In vitro and in vivo effects of phenolic antioxidants against cisplatin-induced nephrotoxicity. J Biochem 1999;125:383â€“90.
20. Rauscher FM, Sanders RA, Watkins 3rd JB. Effect of isoeugenol on oxidative stress pathways in normal and streptozotocin-induced diabetic rats. J Biochem Mol Toxicol 2001;15:159â€“64.
21. Ali S, Prasad R, Mahmood A, Routray I, Shinkafi TS, Sahin K, et al. Eugenol-rich fraction of syzygium aromaticum (Clove) reverses biochemical and histopathological changes in liver cirrhosis and inhibits hepatic cell proliferation. J Cancer Prev 2014;19:288-300.
22. Porto Mde P, da Silva GN, Luperini BC, Bachiega TF, de Castro Marcondes JP, Sforcin JM, et al. Citral and eugenol modulate DNA damage and pro-inflammatory mediator genes in murine peritoneal macrophages. Mol Biol Rep 2014;41:7043-51.
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;388:61-74.
24. Wie MB, Won MH, Lee KH, Shin JH, Lee JC, Suh HW, et al. Eugenol protects neuronal cells from excitotoxic and oxidative injury in primary cortical cultures. Neurosci Lett 1997;225:93-6.
25. Laekeman GM, van Hoof L, Haemers A, Berghe DAV, Herman AG, Vlietinck AJ. Eugenol a valuable compound for in vitro experimental research and worthwhile for further in vivo investigation. Phytother Res 1990;4:90â€“6.
26. Ali SM, Khan AA, Ahmed I, Musaddiq M, Ahmed KS, Polasa H, et al. Antimicrobial activities of eugenol and cinnamaldehyde against the human gastric pathogen Helicobacter pylori. Ann Clin Microbiol Antimicrob 2005;4:20â€“4.
27. Lopez P, Snchez C, Batle R, Nern C. Solid-and vapor-phase antimicrobial activities of six essential oils: susceptibility of selected foodborne bacterial and fungal strains. J Agric Food Chem 2005;53:6939â€“46.
28. van Zyl RL, Seatlholo ST, van Vuuren SF, Viljoen AM. The biological activities of 20 nature identical essential oil constituents. J Essent Oil Res 2006;18:129â€“33.
29. Singh G, Maurya S, DeLampasona MP, Catalan CA. A comparison of chemical, antioxidant and antimicrobial studies of cinnamon leaf and bark volatile oils, oleoresins and their constituents. Food Chem Toxicol 2007;45:1650â€“61.
30. Leite AM, Lima EDO, de Souza EL, Diniz MDFFM, Trajano VN, de Medeiros IA. Inhibitory effect of ÃŸ-pinene, a-pinene and eugenol on the growth of potential infectious endocarditis causing Gram-positive bacteria. Braz J Pharm Sci 2007;43:121â€“6.
31. Hemaiswarya S, Doble M. Synergistic interaction of eugenol with antibiotics against Gram-negative bacteria. Phytomedicine 2009;16:997â€“1005.
32. Oyedemi SO, Okoh AI, Mabinya LV, Pirochenva G, Afolayan AJ. The proposed mechanism of bactericidal action of eugenol, a Î±-terpineol and Î³-terpinene against Listeria monocytogenes, Streptococcus pyogenes, Proteus vulgaris and Escherichia coli. Afr J Biotechnol 2009;8:1280â€“6.
33. Yadav MK, Chae SW, Im GJ, Chung JW, Song JJ. Eugenol: a phyto-compound effective against methicillin-resistant and methicillin-sensitive Staphylococcus aureus clinical strain biofilms. PLoS One 2015;10:e0119564.
34. El abed S, Houari A, Latrache H, Remmal A, Koraichi SI. In vitro activity of four common essential oil components against biofilm-producing Pseudomonas aeruginosa. Res J Microbiol 2011;6:394â€“401.
35. Moon SE, Kim HY, Cha JD. Synergistic effect between clove oil and its major compounds and antibiotics against oral bacteria. Arch Oral Biol 2011;56:907â€“16.
36. Pei RS, Zhou F, Ji BP, Xu J. Evaluation of combined antibacterial effects of eugenol, cinnamaldehyde, thymol and carvacrol against E. coli with an improved method. J Food Sci 2009;74:M379â€“83.
37. Rico-Molina D, Aparicio-Ozores G, Dorantes-Alvarez L, HernÃ¡ndez-Sanchez H. Antimicrobial activity of cinnamate-eugenol: Synergistic potential, evidence of efflux pumps and amino acid effects. Am J Food Technol 2012;7:289â€“300.
38. Qiu J, Feng H, Lu J, Xiang H, Wang D, Dong J, et al. Eugenol reduces the expression of virulence-related exoproteins in Staphylococcus aureus. Appl Environ Microbiol 2010;76:5846â€“51.
39. Zhang P, Zhang E, Xiao M, Chen C, Xu W. Enhanced chemical and biological activities of a newly biosynthesized eugenol glycoconjugate, eugenol Î±-D-glucopyranoside. Appl Microbiol Biotechnol 2013;97:1043-50.
40. Chaieb K, Zmantar T, Ksouri R, Hajlaoui H, Mahdouani K, Abdelly C, et al. Antioxidant properties of the essential oil of Eugenia caryophyllata and its antifungal activity against a large number of clinical Candida species. Mycoses 2007;50:403-6.
41. Abrao PH, Pizi RB, de Souza TB, Silva NC, Fregnan AM, Silva FN, et al. Synthesis and biological evaluation of new eugenol mannich bases as promising antifungal agents. Chem Biol Drug Des 2014;doi: 10.1111/cbdd.12504. [Article in Press].
42. Doke SK, Raut JS, Dhawale S, Karuppayil SM. Sensitization of candida albicans biofilms to fluconazole by terpenoids of plant origin. J Gen Appl Microbiol 2014;60:163-8.
43. De Paula SB, Bartelli TF, Di Raimo V, Santos JP, Morey AT, Bosini MA, et al. Effect of Eugenol on cell surface hydrophobicity, adhesion, and biofilm of Candida tropicalis and Candida dubliniensis isolated from oral cavity of HIV-infected patients. J Evidence Based Complementary Altern Med 2014. doi.org/10.1155/2014/505204. [Article in Press]
44. Khan MS, Ahmad I, Cameotra SS. Phenyl aldehyde and propanoids exert multiple sites of action towards cell membrane and cell wall targeting ergosterol in Candida albicans. AMB Express 2013;3:54.
45. Braga PC, Sasso MD, Culici M, Alfieri M. Eugenol and thymol, alone or in combination, induce morphological alterations in the envelope of Candida albicans. Fitoterapia 2007;78:396-400.
46. Benencia F, Courreges MC. In vitro and in vivo activity of eugenol on human herpesvirus. Phytother Res 2000;14:495-500.
47. Astani A, Reichling J, Schnitzler P. Screening for antiviral activities of isolated compounds from essential oils. J Evidence-Based Complementary Altern Med 2011. doi.org/10.1093/ecam/nep187. [Article in Press]
48. Tragoolpua Y, Jatisatienr A. Anti-herpes simplex virus activities of Eugenia caryophyllus (Spreng.) Bullock and S. G. Harrison and essential oil, eugenol. Phytother Res 2007;21:1153-8.
49. Kurokawa M, Nagasaka K, Hirabayashi T, Uyama S, Sato H, Kageyama T, et al. Efficacy of traditional herbal medicines in combination with acyclovir against herpes simplex virus type 1 infection in vitro and in vivo. Antiviral Res 1995;27:19-37.
50. Yukawa TA, Kurokawa M, Sato H, Yoshida Y, Kageyama S, Hasegawa T, et al. Prophylactic treatment of cytomegalovirus infection with traditional herbs. Antiviral Res 1996;32:63-70.
51. Hussein G, Miyashiro H, Nakamura N, Hattori M, Kakiuchi N, Shimotohno K. Inhibitory effects of sudanese medicinal plant extracts on hepatitis C virus (HCV) protease. Phytother Res 2000;14:510-6.
52. Dai JP, Zhao XF, Zeng J, Wan QY, Yang JC, Li WZ, et al. Drug screening for autophagy inhibitors based on the dissociation of Beclin1-Bcl2 complex using BiFC technique and mechanism of eugenol on anti-influenza A virus activity. PLoS One 2013;8:e61026.
53. Machado M, Dinis AM, Salgueiro L, Custodio JB, Cavaleiro C, Sousa MC. Anti-Giardia activity of Syzygium aromaticum essential oil and eugenol: effects on growth, viability, adherence and ultrastructure. Exp Parasitol 2011;127:732-9.
54. Ueda-Nakamura T, MendonÃ§a-Filho RR, Morgado-Diaz JA, Korehisa Maza P, Prado Dias Filho B, AparÃcio Garcia Cortez D, et al. Antileishmanial activity of Eugenol-rich essential oil from Ocimum. Parasitol Int 2006;55:99-105.
55. Fabri RL, Coimbra gratissimum ES, Almeida AC, Siqueira EP, Alves TM, Zani CL et al. Essential oil of Mitracarpus frigidus as a potent source of bioactive compounds. An Acad Bras Cienc 2012;84:1073-80.
56. Misra P, Kumar A, Khare P, Gupta S, Kumar N, Dube A. Pro-apoptotic effect of the landrace bangla mahoba of piper betle on Leishmania donovani may be due to the high content of eugenol. J Med Microbiol 2009;58:1058-66.
57. de Morais SM, Vila-Nova NS, Bevilaqua CM, Rondon FC, Lobo CH, de Alencar Araripe Noronha Moura A, et al. Thymol and eugenol derivatives as potential antileishmanial agents. Bioorg Med Chem 2014;22:6250â€“5.
58. Santoro GF, Cardoso MG, Guimaraes LG, MendonÃ§a LZ, Soares MJ. Trypanosoma cruzi: activity of essential oils from Achillea millefolium L., Syzygium aromaticum L. and Ocimum basilicum L. on epimastigotes and trypomastigotes. Exp Parasitol 2007;116:283-90.
59. Pisano M, Pagnan G, Loi M, Mura ME, Tilocca MG, Palmieri G, et al. Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells. Molecular Cancer 2007;6:8.
60. Behbahani M. Evaluation of in vitro anticancer activity of Ocimum basilicum, Alhagi maurorum, Calendula officinalis and their parasite Cuscuta campestris. PLoS One 2014;9:e116049.
61. Majeed H, Antoniou J, Fang Z. Apoptotic effects of eugenol-loaded nanoemulsions in human colon and liver cancer cell lines. Asian Pac J Cancer Prev 2014;15:9159-64.
62. Noudogbessi JP, Gary-Bobo M, Adomou A, Adjalian E, Alitonou GA, Avlessi F, et al. Comparative chemical study and cytotoxic activity of Uvariodendron angustifolium essential oils from Benin. Nat Prod Commun 2014;9:261-4.
63. Al-Sharif I, Remmal A, Aboussekhra A. Eugenol triggers apoptosis in breast cancer cells through E2F1/survivin down-regulation. BMC Cancer 2013;13:600.
64. Shamaladevi N, Lyn DA, Shaaban KA, Zhang L, Villate S, Rohr J, et al. Ericifolin-a novel antitumor compound from allspice that silences androgen receptor in prostate cancer. Carcinogenesis 2013;34:1822-32.
65. Koh T, Murakami Y, Tanaka S, Machino M, Onuma H, Kaneko M, et al. Changes of metabolic profiles in an oral squamous cell carcinoma cell line induced by eugenol. In Vivo 2013;27:233-43.
66. 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.
67. Hemaiswarya S, Doble M. Combination of phenylpropanoids with 5-fluorouracil as anti-cancer agents against human cervical cancer (HeLa) cell line. Phytomedicine 2013;20:151-8.
68. Jaganathan SK, Supriyanto E. Antiproliferative and molecular mechanism of eugenol-induced apoptosis in cancer cells. Molecules 2012;17:6290-304.
69. Kim SS, Oh OJ, Min HY, Park EJ, Kim Y, Park HJ, et al. Eugenol suppresses cyclooxygenase-2 expression in lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Life Sci 2003;73:337â€“48.
70. Raghavenra H, Diwakr BT, Lokesh BR, Naidu KA. Eugenolâ€“The active principle from cloves inhibits 5-lipoxygenase activity and leukotriene-C4 in human PMNL cells. Prostaglandins Leukotrienes Essent Fatty Acids 2006;74:23â€“7.