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eugenol |
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CHEBI:4917 |
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A phenylpropanoid formally derived from guaiacol with an allyl chain substituted para to the hydroxy group. It is a major component of clove essential oil, and exhibits antibacterial, analgesic and antioxidant properties. It has been widely used in dentistry to treat toothache and pulpitis. |
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This entity has been manually annotated by the ChEBI Team.
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ChemicalBook:CB7208326, eMolecules:500709, ZINC000000001411 |
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Molfile
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more structures >>
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Eugenol is an allyl chain-substituted guaiacol, a member of the allylbenzene class of chemical compounds. It is a colorless to pale yellow, aromatic oily liquid extracted from certain essential oils especially from clove, nutmeg, cinnamon, basil and bay leaf. It is present in concentrations of 80–90% in clove bud oil and at 82–88% in clove leaf oil. Eugenol has a pleasant, spicy, clove-like scent. The name is derived from Eugenia caryophyllata, the former Linnean nomenclature term for cloves. The currently accepted name is Syzygium aromaticum. |
Read full article at Wikipedia
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InChI=1S/C10H12O2/c1-3-4-8-5-6-9(11)10(7-8)12-2/h3,5-7,11H,1,4H2,2H3 |
RRAFCDWBNXTKKO-UHFFFAOYSA-N |
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Syzygium aromaticum
(NCBI:txid219868)
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See:
DOI
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Homo sapiens
(NCBI:txid9606)
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Found in
blood
(UBERON:0000178).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
saliva
(UBERON:0001836).
See:
PubMed
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radical scavenger
A role played by a substance that can react readily with, and thereby eliminate, radicals.
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sensitiser
A chemical compound that causes a substantial proportion of exposed people or animals to develop an allergic reaction in normal tissue after repeated exposure to the compound.
human blood serum metabolite
Any metabolite (endogenous or exogenous) found in human blood serum samples.
allergen
A chemical compound, or part thereof, which causes the onset of an allergic reaction by interacting with any of the molecular pathways involved in an allergy.
volatile oil component
Any plant metabolite that is found naturally as a component of a volatile oil.
flavouring agent
A food additive that is used to added improve the taste or odour of a food.
EC 1.4.3.4 (monoamine oxidase) inhibitor
An EC 1.4.3.* (oxidoreductase acting on donor CH-NH2 group, oxygen as acceptor) inhibitor that interferes with the action of monoamine oxidase (EC 1.4.3.4).
antibacterial agent
A substance (or active part thereof) that kills or slows the growth of bacteria.
apoptosis inducer
Any substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms.
analgesic
An agent capable of relieving pain without the loss of consciousness or without producing anaesthesia. In addition, analgesic is a role played by a compound which is exhibited by a capability to cause a reduction of pain symptoms.
voltage-gated sodium channel blocker
Any sodium channel blocker that interferes with the activity of voltage-gated sodium channels.
NF-kappaB inhibitor
An inhibitor of NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells), a protein complex involved in the transcription of DNA.
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flavouring agent
A food additive that is used to added improve the taste or odour of a food.
antineoplastic agent
A substance that inhibits or prevents the proliferation of neoplasms.
anaesthetic
Substance which produces loss of feeling or sensation.
analgesic
An agent capable of relieving pain without the loss of consciousness or without producing anaesthesia. In addition, analgesic is a role played by a compound which is exhibited by a capability to cause a reduction of pain symptoms.
anti-inflammatory agent
Any compound that has anti-inflammatory effects.
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View more via ChEBI Ontology
2-methoxy-4-(prop-2-en-1-yl)phenol
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1,3,4-Eugenol
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NIST Chemistry WebBook
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1-allyl-3-methoxy-4-hydroxybenzene
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ChEBI
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1-allyl-4-hydroxy-3-methoxybenzene
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ChEBI
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1-Hydroxy-2-methoxy-4-allylbenzene
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ChemIDplus
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1-Hydroxy-2-methoxy-4-prop-2-enylbenzene
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ChemIDplus
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1-Hydroxy-2-methoxy-4-propenylbenzene
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ChemIDplus
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2-Hydroxy-5-allylanisole
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NIST Chemistry WebBook
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2-Methoxy-1-hydroxy-4-allylbenzene
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ChemIDplus
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2-Methoxy-4-(2-propen-1-yl)phenol
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ChemIDplus
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2-méthoxy-4-(2-propèn-1-yl)phénol
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ChEBI
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2-Methoxy-4-(2-propenyl)phenol
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HMDB
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2-Methoxy-4-allylphenol
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ChemIDplus
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2-methoxy-4-prop-2-enyl-phenol
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PDBeChem
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2-Methoxy-4-prop-2-enylphenol
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ChemIDplus
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4-Allyl-1-hydroxy-2-methoxybenzene
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ChemIDplus
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4-Allyl-2-methoxyphenol
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HMDB
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4-allyl-2-methoxyphenol
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IUPAC
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4-Allylcatechol-2-methyl ether
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NIST Chemistry WebBook
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4-Allylguaiacol
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ChemIDplus
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4-Hydroxy-3-methoxy-1-allylbenzene
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ChemIDplus
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Allylguaiacol
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ChemIDplus
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Caryophyllic acid
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ChemIDplus
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Eugenic acid
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ChemIDplus
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eugenol
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UniProt
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Eugenol
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KEGG COMPOUND
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p-Allylguaiacol
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ChemIDplus
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p-Eugenol
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ChemIDplus
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13876103
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ChemSpider
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2008
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BPDB
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4648
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DrugCentral
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C00000619
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KNApSAcK
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C10453
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KEGG COMPOUND
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CPD-6481
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MetaCyc
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D04117
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KEGG DRUG
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EOL
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PDBeChem
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Eugenol
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Wikipedia
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FDB012171
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FooDB
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HMDB0005809
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HMDB
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LSM-2720
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LINCS
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View more database links |
1366759
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Reaxys Registry Number
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Reaxys
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97-53-0
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CAS Registry Number
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NIST Chemistry WebBook
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97-53-0
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CAS Registry Number
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ChemIDplus
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Ulanowska M, Olas B (2021) Biological Properties and Prospects for the Application of Eugenol-A Review. International journal of molecular sciences 22, 3671 [PubMed:33916044] [show Abstract] Eugenol is a phenolic aromatic compound obtained mainly from clove oil. Due to its known antibacterial, antiviral, antifungal, anticancer, anti-inflammatory and antioxidant properties, it has long been used in various areas, such as cosmetology, medicine, and pharmacology. However, high concentrations can be toxic. A dose of 2.5 mg/kg body weight is regarded as safe. This paper reviews the current state of knowledge regarding the activities and application of eugenol and its derivatives and recent research of these compounds. This review is based on information concerning eugenol characteristics and recent research from articles in PubMed. Eugenol remains of great interest to researchers, since its multidirectional action allows it to be a potential component of drugs and other products with therapeutic potential against a range of diseases. | González-Lugo OE, Pozos-Guillén A, Ponce-Peña P, Lares-Asseff I, Escobar-García DM, Campos-Cantón I, Vértiz-Hernández AA (2020) Synergistic interaction between 4-allyl-1-hydroxy-2-methoxybenzene (eugenol) and diclofenac: An isobolograpic analysis in Wistar rats. Drug development research 81, 978-984 [PubMed:32737935] [show Abstract] Clinical and preclinical research that contributes pain palliation has suggested that drugs favor the expected effects and minimize the adverse effects. Among the most widely used strategies is the combination of analgesic drugs among those in the same group, with those in another group of analgesics or with co-adjuvants (nonanalgesic drugs or elements of traditional medicine). This work aims to evaluate the interaction between eugenol (EUG) and diclofenac (DFC) on nociception in the presence of a noxious stimulus through the formalin test and isobolographic analysis. The results indicate that EUG, DFC, or the combination of both produce an antinociceptive effect in rodents (p ≤ 0.05). Local co-administration of EUG and DFC gave a theoretical effective dose (Zadd ) 2,936.27 ± 155.33 μg/kg (p ≤ 0.05) significantly higher as compared to the effective experimental doses (Zmix ) of 866.89 ± 0.02 μg/kg in phase 1 and 292.88 ± 0.05 μg/kg in phase 2, with an interaction index of 0.29 and 0.09, respectively. These data allow concluding that the interaction derived from the joint administration of EUG and DFC, in the rodent at a local level, is synergistic. | Fernandes MJG, Pereira RB, Pereira DM, Fortes AG, Castanheira EMS, Gonçalves MST (2020) New Eugenol Derivatives with Enhanced Insecticidal Activity. International journal of molecular sciences 21, E9257 [PubMed:33291666] [show Abstract] Eugenol, the generic name of 4-allyl-2-methoxyphenol, is the major component of clove essential oil, and has demonstrated relevant biological potential with well-known antimicrobial and antioxidant actions. New O-alkylated eugenol derivatives, bearing a propyl chain with terminals like hydrogen, hydroxyl, ester, chlorine, and carboxylic acid, were synthesized in the present work. These compounds were later subjected to epoxidation conditions to give the corresponding oxiranes. All derivatives were evaluated against their effect upon the viability of insect cell line Sf9 (Spodoptera frugiperda), demonstrating that structural changes elicit marked effects in terms of potency. In addition, the most promising molecules were evaluated for their impact in cell morphology, caspase-like activity, and potential toxicity towards human cells. Some molecules stood out in terms of toxicity towards insect cells, with morphological assessment of treated cells showing chromatin condensation and fragmentation, which are compatible with the occurrence of programmed cell death, later confirmed by evaluation of caspase-like activity. These findings point out the potential use of eugenol derivatives as semisynthetic insecticides from plant natural products. | Gibbs S, Kosten I, Veldhuizen R, Spiekstra S, Corsini E, Roggen E, Rustemeyer T, Feilzer AJ, Kleverlaan CJ (2018) Assessment of metal sensitizer potency with the reconstructed human epidermis IL-18 assay. Toxicology 393, 62-72 [PubMed:29079364] [show Abstract] According to the new EU Medical Devices (MDR) legislation coming into effect in 2017, manufactures will have to comply with higher standards of quality and safety for medical devices in order to meet common safety concerns regarding such products. Metal alloys are extensively used in dentistry and medicine (e.g. orthopedic surgery and cardiology) even though clinical experience suggests that many metals are sensitizers. The aim of this study was to further test the applicability domain of the in vitro reconstructed human epidermis (RhE) IL-18 assay developed to identify contact allergens and in doing so: i) determine whether different metal salts, representing leachables from metal alloys used in medical devices, could be correctly labelled and classified; and ii) assess the ability of different salts for the same metal to penetrate the skin stratum corneum. Twenty eight chemicals including 15 metal salts were topically exposed to RhE. Nickel, chrome, gold, palladium were each tested in two different salt forms, and titanium in 4 different salt forms. Metal salts were labelled (YES/NO) as sensitizer if a threshold of more than 5 fold IL18 release was reached. The in vitro estimation of expected sensitization induction level (potency) was assessed by interpolating in vitro EC50 and IL-18 SI2 with LLNA EC3 and human NOEL values from standard reference curves generated using DNCB (extreme) and benzocaine (weak). Metal salts, in contrast to other chemical sensitizers and with the exception of potassium dichromate (VI) and cobalt (II) chloride, were not identified as contact allergens since they only induced a small or no increase in IL-18 production. This finding was not related to a lack of stratum corneum skin penetration since EC50 values (decrease in metabolic activity; MTT assay) were obtained after topical RhE exposure to 8 of the 15 metal salts. For nickel, gold and palladium salts, differences in EC50 values between two salts for the same metal could not be attributed to differences in molarity or valency. For chrome salts the difference in EC50 values may be explained by different valencies (VI vs. III), but not by molarity. In general, metal salts were classified as weaker sensitizers than was indicated from in vivo LLNA EC3 and NOEL data. Our in vitro results show that metals are problematic chemicals to test, in line with the limited number of standardized human and animal studies, which are not currently considered adequate to predict systemic hypersensitivity or autoimmunity, and despite clinical experience, which clearly shows that many metals are indeed a risk to human health. | Martínez-Herrera A, Pozos-Guillén A, Ruiz-Rodríguez S, Garrocho-Rangel A, Vértiz-Hernández A, Escobar-García DM (2016) Effect of 4-Allyl-1-hydroxy-2-methoxybenzene (Eugenol) on Inflammatory and Apoptosis Processes in Dental Pulp Fibroblasts. Mediators of inflammation 2016, 9371403 [PubMed:28044068] [show Abstract] Eugenol (mixed with zinc oxide powder) is widely used as direct capping material during pulp therapy in primary teeth. The aim of the present study was to evaluate the effect of eugenol on diverse genes involved in inflammatory and cell apoptosis processes. The regulatory effect of eugenol on the expression of inflammation and apoptotic genes was evaluated in dental pulp fibroblasts from extracted third molars, cultured under concentration of eugenol of 13 μM. Eugenol allowed the expression of inflammatory and apoptotic genes when compared with positive and negative controls. Eugenol is a proinflammatory agent when it is in direct contact with healthy tissues and behaves as an anti-inflammatory agent in tissues undergoing inflammatory/apoptotic processes, as in cases of pulp inflammation in primary teeth. These findings are relevant for dentistry, when considering the application of safer pulp treatments to grossly carious children's teeth. | Wang C, Fan Y (2014) Eugenol enhances the resistance of tomato against tomato yellow leaf curl virus. Journal of the science of food and agriculture 94, 677-682 [PubMed:23852671] [show Abstract]
BackgroundTomato yellow leaf curl virus disease (TYLCVD) causes severe to economic losses in tomato crops in China. The control of TYLCVD is based primarily on the use of synthetic insecticide to control its vector whitefly (Bemisia tabaci). To look for an alternative method for disease control, we investigated the effect of eugenol on controlling TYLCVD. The potential of eugenol to trigger systemic acquired resistance (SAR) in tomato (Jiangsu 14) plants against TYLCV was also investigated.ResultsIn greenhouse experiments, eugenol significantly reduced disease severity when applied as a foliar spray, thus demonstrating a systemic effect. The disease spread rapidly in control plants and by the end of the experiment almost all control plants showed severe symptoms. Eugenol also induced H₂O₂ accumulation in tomato plants. Activities of peroxidase (POD), polyphenol oxidase (PPO) and phenylalanine ammonia lyase (PAL) were significantly induced compared with those of control plants. As further consequences, increase of salicylic acid (SA) levels and expression of PR-1 proteins, a molecular marker of SAR in tomato, could also be observed.ConclusionThis is the first report of eugenol as an elicitor and its ability to suppress plant virus diseases under greenhouse conditions. It is suggested that eugenol has the potential to be an effective biocontrol agent against TYLCV in tomato plants. | Yadav MK, Park SW, Chae SW, Song JJ, Kim HC (2013) Antimicrobial activities of Eugenia caryophyllata extract and its major chemical constituent eugenol against Streptococcus pneumoniae. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 121, 1198-1206 [PubMed:23594212] [show Abstract] In this study, we investigate the antimicrobial activities of both Eugenia caryophyllata (Ec) extract and its major component eugenol (4-allyl-2-methoxyphenol) against Streptococcus pneumoniae. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by microdilution method. Pneumococcal biofilms were detected by crystal-violet microtiter plate assay, followed by colony-forming unit counts and visualized by scanning electron microscope (SEM). The synergistic effect of eugenol and penicillin was determined by checker-board method. Both the eugenol and the Ec extract inhibited pneumococcal growth in a concentration-dependent manner. The MIC and MBC of eugenol were 0.06% and 0.12%, respectively. Eugenol at a concentration of 0.12% completely killed S. pneumoniae within 60 min of exposure. The kill rate of planktonic cells was most rapid during the first 15 min of contact with eugenol. The addition of eugenol or Ec extract inhibited in vitro biofilm formation. In already established biofilms, the inhibitory effect of eugenol or Ec extract was more significant in terms of cell viability than in terms of disruption of the biofilm matrix. SEM analysis revealed non-viable and disruptive action of eugenol on the cell membrane of bacteria of biofilms. It was found that eugenol and penicillin produced a synergistic effect against S. pneumoniae. In conclusion, eugenol and Ec extract efficiently inhibited S. pneumoniae in planktonic growth and within biofilms. | Narayanan A, Neera, Mallesha, Ramana KV (2013) Synergized antimicrobial activity of eugenol incorporated polyhydroxybutyrate films against food spoilage microorganisms in conjunction with pediocin. Applied biochemistry and biotechnology 170, 1379-1388 [PubMed:23666640] [show Abstract] Biopolymers and biopreservatives produced by microorganisms play an essential role in food technology. Polyhydroxyalkanoates and bacteriocins produced by bacteria are promising components to safeguard the environment and for food preservation applications. Polyhydroxybutyrate (PHB)-based antimicrobial films were prepared incorporating eugenol, from 10 to 200 μg/g of PHB. The films were evaluated for antimicrobial activity against foodborne pathogens, spoilage bacteria, and fungi such as Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Bacillus cereus, Aspergillus flavus, Aspergillus niger, Penicillium sp., and Rhizopus sp. The synergistic antimicrobial activity of the films in the presence of crude pediocin was also investigated. The broth system containing pediocin (soluble form) as well as antimicrobial PHB film demonstrated an extended lag phase and a significant growth reduction at the end of 24 h against the bacteria. Crude pediocin alone could not elicit antifungal activity, while inhibition of growth and sporulation were observed in the presence of antimicrobial PHB film containing eugenol (80 μg/g) until 7 days in the case of molds, i.e., A. niger, A. flavus, Penicillium sp., and Rhizopus sp. in potato dextrose broth. In the present study, we identified that use of pediocin containing broth in conjunction with eugenol incorporated PHB film could function in synergized form, providing effective hurdle toward food contaminating microorganisms. Furthermore, tensile strength, percent crystallinity, melting point, percent elongation to break, glass transition temperature, and seal strength of the PHB film with and without eugenol incorporation were investigated. The migration of eugenol on exposure to different liquid food simulants was also analyzed using Fourier transform infrared spectroscopy. The study is expected to provide applications for pediocin in conjunction with eugenol containing PHB film to enhance the shelf life of foods in the food industry. | Zhang P, Zhang E, Xiao M, Chen C, Xu W (2013) Enhanced chemical and biological activities of a newly biosynthesized eugenol glycoconjugate, eugenol α-D-glucopyranoside. Applied microbiology and biotechnology 97, 1043-1050 [PubMed:22923067] [show Abstract] Eugenol, the essential component (over 90 %) of clove oil from Eugenia caryophyllata Thunb. (Myrtaceae), is a phenolic compound well known for its versatile pharmacological actions, including analgesic, local anesthetic, anti-inflammatory, antimicrobial, antitumor, and hair-growing effects. However, the application of eugenol is greatly limited mainly because of its unwanted physicochemical properties, such as low solubility, liability to sublimation, and pungent odor. Since glycosylation has been suggested to improve the physicochemical and biological properties of the parental compound, we have previously developed a novel and efficient way to biosynthesize highly purified eugenol α-D-glucopyranoside (α-EG). In light of the widely acknowledged importance of pure eugenol and the potential superiority of the glycosylation, it is crucial to further explore and compare the physicochemical and biological properties of these two phenolic compounds. In this study, we demonstrate that glucosylation is a promising method for modification of phenolic compound, and that α-EG is superior over its parent eugenol, in all of the tested aspects, including physicochemical properties, antioxidation activity, and antimicrobial and antitumor activities. These results strongly suggest that α-EG, as a novel prodrug, may serve as a useful probe and potential therapeutic drug in both fundamental research and clinical application in the coming future. | Zhang P, Zhang E, Xiao M, Chen C, Xu W (2013) Study of anti-inflammatory activities of α-D-glucosylated eugenol. Archives of pharmacal research 36, 109-115 [PubMed:23325490] [show Abstract] Inflammation is an immune response against a variety of noxious stimuli, such as infection, chemicals, and physical injury. Eugenol, a natural phenolic extract, has drawn much attention for its various desirable pharmacological functions and is, therefore, broadly used in our daily life and medical practice. However, further usage of eugenol is greatly limited due to its unwanted properties, such as physicochemical instability, poor solubility, and high-dose cytotoxicity. In hopes of extending its applicability through glycosylation, we previously reported a novel, efficient, and high throughput way to biosynthesize α-D-glucosylated eugenol (α-EG). In this study, we further explored the potential superior properties of α-EG to its parent eugenol in terms of anti-inflammatory activities. We demonstrated that α-EG was an effective anti-inflammatory mediator in both non-cellular and cellular environments. In addition, the non-cellular inhibitory effect of α-EG could be amplified by α-glucosidase, which ubiquitously exists in cytoplasm. Furthermore, α-EG exhibited a superior anti-inflammatory effect to its parent eugenol in a cellular environment. In words, our findings collectively suggest that α-EG is a stronger anti-inflammatory mediator and may thereby serve as a desirable substitute for eugenol and a potential therapeutic prodrug in treating inflammatory diseases in the future. | Devi KP, Sakthivel R, Nisha SA, Suganthy N, Pandian SK (2013) Eugenol alters the integrity of cell membrane and acts against the nosocomial pathogen Proteus mirabilis. Archives of pharmacal research 36, 282-292 [PubMed:23444040] [show Abstract] Eugenol, a member of the phenylpropanoids class of chemical compounds, is a clear to pale yellow oily liquid extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, and bay leaf. The antibacterial activity of eugenol and its mechanism of bactericidal action against Proteus mirabilis were evaluated. Treatment with eugenol at their minimum inhibitory concentration [0.125 % (v/v)] and minimum bactericidal concentration [0.25 % (v/v)] reduced the viability and resulted in complete inhibition of P. mirabilis. A strong bactericidal effect on P. mirabilis was also evident, as eugenol inactivated the bacterial population within 30 min exposure. Chemo-attractant property and the observance of highest antibacterial activity at alkaline pH suggest that eugenol can work more effectively when given in vivo. Eugenol inhibits the virulence factors produced by P. mirabilis as observed by swimming motility, swarming behavior and urease activity. It interacts with cellular membrane of P. mirabilis and makes it highly permeable, forming nonspecific pores on plasma membrane, which in turn directs the release of 260 nm absorbing materials and uptake of more crystal violet from the medium into the cells. SDS-polyacrylamide gel, scanning electron microscopy and Fourier transform infrared analysis further proves the disruptive action of eugenol on the plasma membrane of P. mirabilis. The findings reveal that eugenol shows an excellent bactericidal activity against P. mirabilis by altering the integrity of cell membrane. | Koeduka T, Suzuki S, Iijima Y, Ohnishi T, Suzuki H, Watanabe B, Shibata D, Umezawa T, Pichersky E, Hiratake J (2013) Enhancement of production of eugenol and its glycosides in transgenic aspen plants via genetic engineering. Biochemical and biophysical research communications 436, 73-78 [PubMed:23707945] [show Abstract] Eugenol, a volatile phenylpropene found in many plant species, exhibits antibacterial and acaricidal activities. This study attempted to modify the production of eugenol and its glycosides by introducing petunia coniferyl alcohol acetyltransferase (PhCFAT) and eugenol synthase (PhEGS) into hybrid aspen. Gas chromatography analyses revealed that wild-type hybrid aspen produced small amount of eugenol in leaves. The heterologous overexpression of PhCFAT alone resulted in up to 7-fold higher eugenol levels and up to 22-fold eugenol glycoside levels in leaves of transgenic aspen plants. The overexpression of PhEGS alone resulted in a subtle increase in either eugenol or eugenol glycosides, and the overexpression of both PhCFAT and PhEGS resulted in significant increases in the levels of both eugenol and eugenol glycosides which were nonetheless lower than the increases seen with overexpression of PhCFAT alone. On the other hand, overexpression of PhCFAT in transgenic Arabidopsis and tobacco did not cause any synthesis of eugenol. These results indicate that aspen leaves, but not Arabidopsis and tobacco leaves, have a partially active pathway to eugenol that is limited by the level of CFAT activity and thus the flux of this pathway can be increased by the introduction of a single heterologous gene. | Zhou L, Zheng H, Tang Y, Yu W, Gong Q (2013) Eugenol inhibits quorum sensing at sub-inhibitory concentrations. Biotechnology letters 35, 631-637 [PubMed:23264268] [show Abstract]
UnlabelledIn bacteria, quorum sensing (QS) is a process of chemical communication involving the production, release, and subsequent detection of signaling molecules. QS regulates the production of key virulence factors in pathogens. During the screening of herbal extracts, clove extract was found to inhibit QS-controlled gene expression in Pseudomonas aeruginosa QSIS-lasI and Chromobacterium violaceum CV026 biosensors. Using a bioautographic TLC assay, preparative TLC, and HPLC analysis, eugenol, the major constituent of clove extract, exhibited QS inhibitory activity. Eugenol at sub-inhibitory concentrations inhibited the production of virulence factors, including violacein, elastase, pyocyanin, and biofilm formation. Using two Escherichia coli biosensors, MG4/pKDT17 and pEAL08-2, we confirmed that eugenol inhibited the las and pqs QS systems. Our data identified eugenol as a novel QS inhibitor.Purpose of the workThe purpose of this study was to track the quorum sensing inhibitor (QSI) in herbal extracts by effective screening systems and evaluate its biological activity. The QSIs from herbal extracts are potential agents for the treatment of bacterial infections. | Woranuch S, Yoksan R (2013) Eugenol-loaded chitosan nanoparticles: I. Thermal stability improvement of eugenol through encapsulation. Carbohydrate polymers 96, 578-585 [PubMed:23768603] [show Abstract] The objective of the present work was to improve the thermal stability of eugenol by encapsulating into chitosan nanoparticles via an emulsion-ionic gelation crosslinking method. The influences of the initial eugenol content and tripolyphosphate (TPP) concentration on the loading capacity (LC), encapsulation efficiency (EE), morphology and surface charge of the eugenol-loaded chitosan nanoparticles were also investigated. LC and EE tended to increase with increasing initial eugenol content and decreasing TPP concentration. Particles with LC of 12% and EE of 20% exhibited a spherical shape with an average size of less than 100 nm. Thermal stability of the encapsulated eugenol was verified through its extrusion at 155°C with a model plastic, i.e. thermoplastic flour (TPF). TPF containing encapsulated eugenol showed 8-fold higher remaining eugenol content and 2.7-fold greater radical scavenging activity than that containing naked eugenol. The results suggest the possible use of eugenol-loaded chitosan nanoparticles as antioxidants in bioactive plastics for food packaging. | Woranuch S, Yoksan R (2013) Eugenol-loaded chitosan nanoparticles: II. Application in bio-based plastics for active packaging. Carbohydrate polymers 96, 586-592 [PubMed:23768604] [show Abstract] The aim of the present research was to study the possibility of using eugenol-loaded chitosan nanoparticles as antioxidants for active bio-based packaging material. Eugenol-loaded chitosan nanoparticles were incorporated into thermoplastic flour (TPF) - a model bio-based plastic - through an extrusion process at temperatures above 150°C. The influences of eugenol-loaded chitosan nanoparticles on crystallinity, morphology, thermal properties, radical scavenging activity, reducing power, tensile properties and barrier properties of TPF were investigated. Although the incorporation of 3% (w/w) of eugenol-loaded chitosan nanoparticles significantly reduced the extensibility and the oxygen barrier property of TPF, it provided antioxidant activity and improved the water vapor barrier property. In addition, TPF containing eugenol-loaded chitosan nanoparticles exhibited superior radical scavenging activity and stronger reducing power compared with TPF containing naked eugenol. The results suggest the applicability of TPF containing eugenol-loaded chitosan nanoparticles as an antioxidant active packaging material. | Koch T, Peutzfeldt A, Malinovskii V, Flury S, Häner R, Lussi A (2013) Temporary zinc oxide-eugenol cement: eugenol quantity in dentin and bond strength of resin composite. European journal of oral sciences 121, 363-369 [PubMed:23841789] [show Abstract] Uptake of eugenol from eugenol-containing temporary materials may reduce the adhesion of subsequent resin-based restorations. This study investigated the effect of duration of exposure to zinc oxide-eugenol (ZOE) cement on the quantity of eugenol retained in dentin and on the microtensile bond strength (μTBS) of the resin composite. The ZOE cement (IRM Caps) was applied onto the dentin of human molars (21 per group) for 1, 7, or 28 d. One half of each molar was used to determine the quantity of eugenol (by spectrofluorimetry) and the other half was used for μTBS testing. The ZOE-exposed dentin was treated with either OptiBond FL using phosphoric acid (H₃PO₄) or with Gluma Classic using ethylenediaminetetraacetic acid (EDTA) conditioning. One group without conditioning (for eugenol quantity) and two groups not exposed to ZOE (for eugenol quantity and μTBS testing) served as controls. The quantity of eugenol ranged between 0.33 and 2.9 nmol mg⁻¹ of dentin (median values). No effect of the duration of exposure to ZOE was found. Conditioning with H₃PO₄ or EDTA significantly reduced the quantity of eugenol in dentin. Nevertheless, for OptiBond FL, exposure to ZOE significantly decreased the μTBS, regardless of the duration of exposure. For Gluma Classic, the μTBS decreased after exposure to ZOE for 7 and 28 d. OptiBond FL yielded a significantly higher μTBS than did Gluma Classic. Thus, ZOE should be avoided in cavities later to be restored with resin-based materials. | Xu JS, Li Y, Cao X, Cui Y (2013) The effect of eugenol on the cariogenic properties of Streptococcus mutans and dental caries development in rats. Experimental and therapeutic medicine 5, 1667-1670 [PubMed:23837051] [show Abstract] Eugenol has been widely used in medicine due to its antibacterial, anti-inflammatory, antioxidant, anticancer and analgesic properties. The present study was designed to investigate the effects of eugenol on the cariogenic properties of Streptococcus mutans and dental caries development in rats. Eugenol demonstrated significant inhibitory effects against acid production by S. mutans. The synthesis of water-insoluble glucans by glucosyltransferases was reduced by eugenol. Eugenol also markedly suppressed the adherence of S. mutans to saliva-coated hydroxyapatite beads. Furthermore, topical application of eugenol reduced the incidence and severity of carious lesions in rats. These results suggest that the natural compound eugenol may be a useful therapeutic agent for dental caries. | Nam H, Kim MM (2013) Eugenol with antioxidant activity inhibits MMP-9 related to metastasis in human fibrosarcoma cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 55, 106-112 [PubMed:23313798] [show Abstract] The oxidative damage of lipid, protein and DNA is known to be involved in chronic inflammation as well as metastasis. It has been highlighted for searching natural compounds without toxicity to prevent development of these diseases. Thus, it was investigated whether eugenol can inhibit matrix metalloproteinase (MMP) expression and activity as well as antioxidant effect. Eugenol was contained as a major ingredient in herbs such as clove and Magnoliae Flos. The direct scavenging effects of eugenol on DPPH radical, hydrogen peroxide, reducing power, lipid peroxidation and genomic DNA damage related to oxidative stress were evaluated in cell free system. It was observed that eugenol specifically exhibited higher inhibitory effect on hydrogen peroxide than other reactive oxygen species, and also blocked DNA oxidation and lipid peroxidation induced by hydroxyl radical. In addition, the inhibitory effects of eugenol on the activity and expression of MMP-9 activity related to metastasis were determined using gelatin zymography and western-blot. The data showed that it inhibited MMP-9 activities in PMA-stimulated HT1080 cells. Furthermore, it was found that eugenol exerts inhibitory effects on MMP-9 via inactivation of ERK. Therefore, these results suggest that eugenol could be available as an excellent agent for prevention of metastasis related to oxidative stress. | Koh T, Murakami Y, Tanaka S, Machino M, Onuma H, Kaneko M, Sugimoto M, Soga T, Tomita M, Sakagami H (2013) Changes of metabolic profiles in an oral squamous cell carcinoma cell line induced by eugenol. In vivo (Athens, Greece) 27, 233-243 [PubMed:23422484] [show Abstract]
BackgroundWe have recently reported that eugenol exerted indiscriminate cytotoxicity towards normal oral cells and oral squamous cell carcinoma (OSCC) cell lines without induction of apoptosis markers. In order to investigate the underlying mechanisms of cytotoxicity induction, we investigated the effect of short-term treatment with eugenol on the metabolic profiles of a human OSCC cell line (HSC-2).Materials and methodsThe viable cell number was determined by direct cell counting with a hemocytometer after trypsinization. After washing with 5% D-mannitol solution (found to retain the highest amounts of intracellular metabolites among several washing conditions), cellular metabolites were extracted with methanol with internal markers and then subjected to metabolomic analysis.ResultsCytotoxic concentrations of eugenol induced the reduction of ATP utilization (assessed by a significant reduction of the AMP/ATP and ADP/ATP ratio), of oxidative stress (assessed by the increase in oxidized form of glutathione, cysteine-glutathione disulfide and methionine sulfoxide), and an increase in the polyamines and glycolytic metabolites.ConclusionThe metabolic changes observed in this study suggest the induction of non-apoptotic cell death by eugenol. | Koh T, Murakami Y, Tanaka S, Machino M, Sakagami H (2013) Re-evaluation of anti-inflammatory potential of eugenol in IL-1β-stimulated gingival fibroblast and pulp cells. In vivo (Athens, Greece) 27, 269-273 [PubMed:23422489] [show Abstract]
BackgroundWe recently reported that eugenol exerted comparable cytotoxicity towards human normal and tumor cells. In the present study, we investigated the effect of eugenol on interleukin-8 (IL-8) production by IL-1β-stimulated oral cells.Materials and methodsThe viable cell number was determined by direct cell counting with a hemocytometer after trypsinization. IL-8 released into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA).ResultsIL-1β (5 ng/ml) induced two orders of magnitude higher production of IL-8 by human cultured cells than unstimulated cells. Upon IL-1β stimulation, both gingival fibroblasts (HGF) and periodontal ligament fibroblasts (HPLF) produced the greatest amounts of IL-8 (approximately 200-300 ng/ml), followed by pulp cells (HPCs) (approximately 40-50 ng/ml), whereas skin keratinocyte (HaCat) and oral squamous cell carcinoma cells (HSC-2, HSC-4) produced much less IL-8 (less than 15 ng/ml). The production of IL-8 depended on growth factor(s), since the omission of fetal bovine serum from the culture medium resulted in an approximately 90% decline of IL-8 production. Eugenol (5-500 μM) significantly stimulated IL-8 production in HGF cells, but had bi-modal effects on HPCs, causing slight stimulation at lower concentration (5 μM) and a significant inhibition at higher concentration (500 μM), regardless of the presence or absence of serum. Eugenol exerted similar effects on lipopolysaccharide-stimulated HGFs and HPCs.ConclusionThese results demonstrate that an anti-inflammatory effect of eugenol is observed in HPCs, but not in HGFs. The narrow therapeutic range of eugenol suggests the importance of careful usage of this compound for dental treatment. | Shah B, Davidson PM, Zhong Q (2013) Nanodispersed eugenol has improved antimicrobial activity against Escherichia coli O157:H7 and Listeria monocytogenes in bovine milk. International journal of food microbiology 161, 53-59 [PubMed:23261812] [show Abstract] There has been great interest in intervention strategies based on plant essential oils to control pathogens such as Escherichia coli O157:H7 and Listeria monocytogenes (Lm). However, the poor solubility of essential oils in water makes it difficult to disperse evenly in food matrices, impacting food quality and antimicrobial efficacy. In the present study, eugenol was dispersed in nanocapsules prepared with conjugates of whey protein isolate (WPI) and maltodextrin (MD, of various chain lengths). When eugenol was encapsulated in the conjugate made with MD40 at a WPI:MD mass ratio of 1:2, the nanodispersion was transparent and was characterized for antimicrobial efficacy against E. coli O157:H7 strains ATCC 43889 and 43894, and Lm strains Scott A and 101 in tryptic soy broth (TSB) and milk with different fat levels (whole, 2% reduced fat, and skim) at 35 or 32 °C, with comparison to the same levels of free eugenol. In TSB, antimicrobial efficacy of nanodispersed eugenol against E. coli O157:H7 and Lm was not improved, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values being 0.25 g/L higher than those of free eugenol. Free eugenol performed better in TSB because there was no interfering compound and the MIC and MBC were below the solubility of eugenol. In milk, nanodispersed eugenol was consistently observed to be more effective than free eugenol, with MIC and MBC values above the solubility limit of eugenol. The nanodispersed eugenol was speculated to be evenly distributed in food matrices at concentrations above the solubility limit and supplied the antimicrobial locally when the binding caused eugenol level below the inhibition requirement. Nanodispersed eugenol thus provides a novel approach for incorporation in foods to improve antimicrobial efficacy without changing turbidity. | de Oliveira Pereira F, Mendes JM, de Oliveira Lima E (2013) Investigation on mechanism of antifungal activity of eugenol against Trichophyton rubrum. Medical mycology 51, 507-513 [PubMed:23181601] [show Abstract] Trichophyton rubrum is a worldwide agent responsible for chronic cases of dermatophytosis which have high rates of resistance to antifungal drugs. Attention has been drawn to the antimicrobial activity of aromatic compounds because of their promising biological properties. Therefore, we investigated the antifungal activity of eugenol against 14 strains of T. rubrum which involved determining its minimum inhibitory concentration (MIC) and effects on mycelial growth (dry weight), conidial germination and morphogenesis. The effects of eugenol on the cell wall (sorbitol protect effect) and the cell membrane (release of intracellular material, complex with ergosterol, ergosterol synthesis) were investigated. Eugenol inhibited the growth of 50% of T. rubrum strains employed in this study at an MIC = 256 μg/ml, as well as mycelial growth and conidia germination. It also caused abnormalities in the morphology of the dermatophyte in that we found wide, short, twisted hyphae and decreased conidiogenesis. The results of these studies on the mechanisms of action suggested that eugenol exerts antifungal effects on the cell wall and cell membrane of T. rubrum. Eugenol act on cell membrane by a mechanism that seems to involve the inhibition of ergosterol biosynthesis. The lower ergosterol content interferes with the integrity and functionality of the cell membrane. Finally, our studies support the potential use of the eugenol as an antifungal agent against T. rubrum. | Klein AH, Carstens MI, Carstens E (2013) Eugenol and carvacrol induce temporally desensitizing patterns of oral irritation and enhance innocuous warmth and noxious heat sensation on the tongue. Pain 154, 2078-2087 [PubMed:23791894] [show Abstract] Eugenol and carvacrol, from the spices clove and oregano, respectively, are agonists of TRPV3, which is implicated in transduction of warmth and possibly heat pain. We investigated the temporal dynamics of lingual irritation elicited by these agents, and their effects on innocuous warmth and heat pain, using a half-tongue method in human subjects. The irritant sensation elicited by both eugenol and carvacrol decreased across repeated applications at a 1-minute interstimulus interval (self-desensitization) which persisted for at least 10 minutes. Both agents also cross-desensitized capsaicin-evoked irritation. Eugenol and carvacrol significantly increased the magnitude of perceived innocuous warmth (44 °C) for >10 minutes, and briefly (<5 minutes) enhanced heat pain elicited by a 49 °C stimulus. Similar albeit weaker effects were observed when thermal stimuli were applied after the tongue had been desensitized by repeated application of eugenol or carvacrol, indicating that the effect is not due solely to summation of chemoirritant and thermal sensations. Neither chemical affected sensations of innocuous cool or cold pain. A separate group of subjects was asked to subdivide eugenol and carvacrol irritancy into subqualities, the most frequently reported being numbing and warmth, with brief burning, stinging/pricking, and tingle, confirming an earlier study. Eugenol, but not carvacrol, reduced detection of low-threshold mechanical stimuli. Eugenol and carvacrol enhancement of innocuous warmth may involve sensitization of thermal gating of TRPV3 expressed in peripheral warm fibers. The brief heat hyperalgesia following eugenol may involve a TRPV3-mediated enhancement of thermal gating of TRPV1 expressed in lingual polymodal nociceptors. | Rastogi S, Kumar R, Chanotiya CS, Shanker K, Gupta MM, Nagegowda DA, Shasany AK (2013) 4-coumarate: CoA ligase partitions metabolites for eugenol biosynthesis. Plant & cell physiology 54, 1238-1252 [PubMed:23677922] [show Abstract] Biosynthesis of eugenol shares its initial steps with that of lignin, involving conversion of hydroxycinnamic acids to their corresponding coenzyme A (CoA) esters by 4-coumarate:CoA ligases (4CLs). In this investigation, a 4CL (OS4CL) was identified from glandular trichome-rich tissue of Ocimum sanctum with high sequence similarity to an isoform (OB4CL_ctg4) from Ocimum basilicum. The levels of OS4CL and OB4CL_ctg4-like transcripts were highest in O. sanctum trichome, followed by leaf, stem and root. The eugenol content in leaf essential oil was positively correlated with the expression of OS4CL in the leaf at different developmental stages. Recombinant OS4CL showed the highest activity with p-coumaric acid, followed by ferulic, caffeic and trans-cinnamic acids. Transient RNA interference (RNAi) suppression of OS4CL in O. sanctum leaves caused a reduction in leaf eugenol content and trichome transcript level, with a considerable increase in endogenous p-coumaric, ferulic, trans-cinnamic and caffeic acids. A significant reduction in the expression levels was observed for OB4CL_ctg4-related transcripts in suppressed trichome compared with transcripts similar to the other four isoforms (OB4CL_ctg1, 2, 3 and 5). Sinapic acid and lignin content were also unaffected in RNAi suppressed leaf samples. Transient expression of OS4CL-green fluorescent protein fusion protein in Arabidopsis protoplasts was associated with the cytosol. These results indicate metabolite channeling of intermediates towards eugenol by a specific 4CL and is the first report demonstrating the involvement of 4CL in creation of virtual compartments through substrate utilization and committing metabolites for eugenol biosynthesis at an early stage of the pathway. | Spinelli S, Lagarde A, Iovinella I, Legrand P, Tegoni M, Pelosi P, Cambillau C (2012) Crystal structure of Apis mellifera OBP14, a C-minus odorant-binding protein, and its complexes with odorant molecules. Insect biochemistry and molecular biology 42, 41-50 [PubMed:22075131] [show Abstract] Apis mellifera (Amel) relies on its olfactory system to detect and identify new-sources of floral food. The Odorant-Binding Proteins (OBPs) are the first proteins involved in odorant recognition and interaction, before activation of the olfactory receptors. The Amel genome possess a set of 21 OBPs, much fewer compared to the 60-70 OBPs found in Diptera genomes. We have undertaken a structural proteomics study of Amel OBPs, alone or in complex with odorant or model compounds. We report here the first 3D structure of a member of the C-minus class OBPs, AmelOBP14, characterized by only two disulfide bridges of the three typical of classical OBPs. We show that AmelOBP14 possesses a core of 6 α-helices comparable to that of classical OBPs, and an extra exposed C-terminal helix. Its binding site is located within this core and is completely closed. Fluorescent experiments using 1-NPN displacement demonstrate that AmelOBP14 is able to bind several compounds with sub micromolar dissociation constants, among which citralva and eugenol exhibit the highest affinities. We have determined the structures of AmelOBP14 in complex with 1-NPN, eugenol and citralva, explaining their strong binding. Finally, by introducing a double cysteine mutant at positions 44 and 97, we show that a third disulfide bridge was formed in the same position as in classical OBPs without disturbing the fold of AmelOBP14. | Soini HA, Klouckova I, Wiesler D, Oberzaucher E, Grammer K, Dixon SJ, Xu Y, Brereton RG, Penn DJ, Novotny MV (2010) Analysis of volatile organic compounds in human saliva by a static sorptive extraction method and gas chromatography-mass spectrometry. Journal of chemical ecology 36, 1035-1042 [PubMed:20809147] [show Abstract] Human saliva not only helps control oral health (with anti-microbial proteins), but it may also play a role in chemical communication. As is the case with other mammalian species, human saliva contains peptides, proteins, and numerous volatile organic compounds (VOCs). A high-throughput analytical method is described for profiling a large number of saliva samples to screen the profiles of VOCs. Saliva samples were collected in a non-stimulated fashion. The method utilized static stir bar extraction followed by gas chromatography-mass spectrometry (GC-MS). The method provided excellent reproducibility for a wide range of salivary compounds, including alcohols, aldehydes, ketones, carboxylic acids, esters, amines, amides, lactones, and hydrocarbons. Furthermore, substantial overlap of salivary VOCs and the previously reported skin VOCs in the same subject group was found in this study by using pattern recognition analyses. Sensitivity, precision, and reproducibility of the method suggest that this technique has potential in physiological, metabolomic, pharmacokinetic, forensic, and toxicological studies of small organic compounds where a large number of human saliva samples are involved. | Chung G, Rhee JN, Jung SJ, Kim JS, Oh SB (2008) Modulation of CaV2.3 calcium channel currents by eugenol. Journal of dental research 87, 137-141 [PubMed:18218839] [show Abstract] Eugenol, a natural congener of capsaicin, is a routine analgesic agent in dentistry. We have recently demonstrated the inhibition of Ca(V)2.2 calcium channel and sodium channel currents to be molecular mechanisms underlying the analgesic effect of eugenol. We hypothesized that Ca(V)2.3 channels are also modulated by eugenol and investigated its mode of action using the whole-cell patch-clamp technique in a heterologous expression system. Eugenol inhibited calcium currents in the E52 cell line, stably expressing the human Ca(V)2.3 calcium channels, where TRPV1 is not endogenously expressed. The extent of current inhibition was not significantly different between naïve E52 cells and TRPV1-expressing E52 cells, suggesting no involvement of TRPV1. In contrast, TRPV1 activation is prerequisite for the inhibition of Ca(V)2.3 calcium channels by capsaicin. The results indicate that eugenol has mechanisms distinct from those of capsaicin for modulating Ca(V)2.3 channels. We suggest that inhibition of Ca(V)2.3 channels by eugenol might contribute to its analgesic effect. | Ghosh R, Nadiminty N, Fitzpatrick JE, Alworth WL, Slaga TJ, Kumar AP (2005) Eugenol causes melanoma growth suppression through inhibition of E2F1 transcriptional activity. The Journal of biological chemistry 280, 5812-5819 [PubMed:15574415] [show Abstract] Metastatic malignant melanoma is an extremely aggressive cancer, with no currently viable therapy. 4-Allyl-2-methoxyphenol (eugenol) was tested for its ability to inhibit proliferation of melanoma cells. Eugenol but not its isomer, isoeugenol (2-methoxy-4-propenylphenol), was found to be a potent inhibitor of melanoma cell proliferation. In a B16 xenograft study, eugenol treatment produced a significant tumor growth delay (p = 0.0057), an almost 40% decrease in tumor size, and a 19% increase in the median time to end point. More significantly, 50% of the animals in the control group died from metastatic growth, whereas none in the treatment group showed any signs of invasion or metastasis. Eugenol was well tolerated as determined by measurement of bodyweights. Examination of the mechanism of the antiproliferative action of eugenol in the human malignant melanoma cell line, WM1205Lu, showed that it arrests cells in the S phase of the cell cycle. Flow cytometry coupled with biochemical analyses demonstrated that eugenol induced apoptosis. cDNA array analysis showed that eugenol caused deregulation of the E2F family of transcription factors. Transient transfection assays and electrophoretic mobility shift assays showed that eugenol inhibits the transcriptional activity of E2F1. Overexpression of E2F1 restored about 75% of proliferation ability in cultures. These results indicate that deregulation of E2F1 may be a key factor in eugenol-mediated melanoma growth inhibition both in vitro and in vivo. Since the E2F transcription factors provide growth impetus for the continuous proliferation of melanoma cells, these results suggest that eugenol could be developed as an E2F-targeted agent for melanoma treatment. | Takeyoshi M, Noda S, Yamazaki S, Kakishima H, Yamasaki K, Kimber I (2004) Assessment of the skin sensitization potency of eugenol and its dimers using a non-radioisotopic modification of the local lymph node assay. Journal of applied toxicology : JAT 24, 77-81 [PubMed:14745850] [show Abstract] Allergic contact dermatitis is a serious health problem. There is a need to identify and characterize skin sensitization hazards, particularly with respect to relative potency, so that accurate risk assessments can be developed. For these purposes the murine local lymph node assay (LLNA) was developed. Here, we have investigated further a modi fi cation of this assay, non-radioisotopic LLNA, which in place of tritiated thymidine to measure lymph node cell proliferation employs incorporation of 5-bromo-2'-deoxyuridine. Using this method we have examined the skin sensitizing activity of eugenol, a known human contact allergen, and its dimers 2,2'-dihydroxyl-3,3'-dimethoxy-5,5'-diallyl-biphenyl (DHEA) and 4,5'-diallyl-2'-hydroxy-2,3'-dimethoxy phenyl ether (DHEB). Activity in the guinea pig maximization test (GPMT) also measured. On the basis of GPMT assays, eugenol was classified as a mild skin sensitizer, DHEA as a weak skin sensitizer and DHEB as an extreme skin sensitizer. In the non-radioisotopic LLNA all chemicals were found to give positive responses insofar as each was able to provoke a stimulation index (SI) of >or=3 at one or more test concentrations. The relative skin sensitizing potency of these chemicals was evaluated in the non-radioisotopic LLNA by derivation of an ec(3) value (the concentration of chemical required to provoke an SI of 3). The ec(3) values calculated were 25.1% for eugenol, >30% for DHEA and 2.3% for DHEB. Collectively these data suggest that assessments of relative potency deriving from non-radioisotopic LLNA responses correlate well with evaluations based on GPMT results. These investigations provide support for the proposal that the non-radioisotopic LLNA may serve as an effective alternative to the GPMT where there is a need to avoid the use of radioisotopes. | Fujisawa S, Okada N, Muraoka E (2001) Comparative effects of eugenol to bis-eugenol on oral mucous membranes. Dental materials journal 20, 237-242 [PubMed:11806158] [show Abstract] The purpose of this study was to evaluate the histopathological effect of eugenol and bis-eugenol on oral mucous membranes at the tissue organ level. Oral mucous membranes of mice were applied with three reagents, eugenol, bis-eugenol, and acetone (as the control). The control group showed a normal architecture. The eugenol group showed severe hyperkeratosis, parakeratosis, cellular edema, patchy chronic inflammation, pleomorphism and hyperchromatism of basal layer cells, indicating high mitotic activity. Comparatively, the bis-eugenol group showed mild hyperkeratosis, parakeratosis, however, the shape or arrangement of basal layer cells were normal. Bis-eugenol was considerably less toxic than eugenol. | Guironnet G, Dalbiez-Gauthier C, Rousset F, Schmitt D, Péguet-Navarro J (2000) In vitro human T cell sensitization to haptens by monocyte-derived dendritic cells. Toxicology in vitro : an international journal published in association with BIBRA 14, 517-522 [PubMed:11033063] [show Abstract] We previously reported that in vitro primary sensitization of hapten-specific T cells by cultured human epidermal Langerhans cells (LC) provides an alternative approach to discriminate strong contact sensitizers from irritants (Krasteva et al., 1996; Moulon et al., 1993). However, this LC-based immunoassay was limited by the availability of human skin samples. In the present study, we used monocyte-derived dendritic cells (DC) to analyse the autologous proliferative T cell response to several allergens. Monocytes were purified from the peripheral blood of healthy donors and cultured for 6-8 days in the presence of GM/CSF and IL-4 and then for 2 days in the presence of GM/CSF and TNFalpha. The resulting cells exhibited the phenotype of mature DC, as assessed by the strong expression of HLA-DR, CD80, CD83 and CD86 antigens. We showed that trinitrophenyl (TNP)-treated mature DC induced a significant T cell proliferative response in all experiments, while fluorescein isothiocyanate (FITC) gave positive results in about half of them. The prohaptens eugenol and isoeugenol induced significant proliferation in one out of eight and in four out of 12 experiments, respectively. Interestingly, in 16 assays T cells never proliferated in the presence of sodium lauryl sulfate (SLS)-treated DC. Thus, this in vitro model allows discrimination between strong contact sensitizers and irritants. It might be very useful, therefore, for restriction of animal experimentation. | Bertrand F, Basketter DA, Roberts DW, Lepoittevin JP (1997) Skin sensitization to eugenol and isoeugenol in mice: possible metabolic pathways involving ortho-quinone and quinone methide intermediates. Chemical research in toxicology 10, 335-343 [PubMed:9084914] [show Abstract] With the aim of providing further mechanistic insights into the mode of action of eugenol (4-allyl-2-methoxyphenol) and isoeugenol (4-propenyl-2-methoxyphenol), we have synthesized two series of modified compounds which were tested in the mouse local lymph node assay for their skin sensitizing potential. The replacement of the methoxy group by an isopropoxy group led to a complete loss of sensitization for the eugenol derivative 6a, while no significant effect was observed for the isoeugenol derivative 6b. In the eugenol series, when methyl groups were present in the 3-, 5-, or 6-position a significant reduction in sensitization potential was observed while in the isoeugenol series only methyl substitution in the 3- and 5-position had a discernable effect. Introduction of three methyl groups on the aromatic ring of eugenol (3,5,6-trimethyl-4-allyl-2-methoxyphenol, 7) and of a tert-butyl substituent at the gamma-position of the alkyl chain of isoeugenol (4-[3',3',3'-trimethylpropenyl]-2-methoxyphenol, 8) led to a strong decrease of the sensitizing capacity. Our findings indicate that, at least in the mouse, eugenol could sensitize via a demethylation pathway followed by oxidation to the o-quinone which could act directly as a hapten even if we cannot exclude a reaction via its tautomeric p-quinone methide. Isoeugenol, on the other hand, could act via a mechanism not involving demethylation and for which the evidence is consistent with a direct oxidation to the p-quinone methide. | Naidu KA (1995) Eugenol--an inhibitor of lipoxygenase-dependent lipid peroxidation. Prostaglandins, leukotrienes, and essential fatty acids 53, 381-383 [PubMed:8596779] [show Abstract] The effect of eugenol on enzymatic lipid peroxidation catalyzed by soybean lipoxygenase was studied in an in vitro system. Lipid peroxidation was inhibited by eugenol in a concentration-dependent manner. The half-maximal inhibition (IC50) was found to be 380 microM eugenol. Enzyme kinetic studies showed that eugenol non-competitively inhibited lipid peroxidation by altering the maximum velocity (Vmax) and without any change in Michaelis-Menten constant (Km) values. The inhibitory mechanism implies that eugenol does not inactivate the enzyme directly but may interfere with fatty acid radical intermediates due to its hydroxy radical scavenging ability and thus play a role in inhibiting the propagation of lipid peroxidation. | Fischer IU, Dengler HJ (1990) Sensitive high-performance liquid chromatographic assay for the determination of eugenol in body fluids. Journal of chromatography 525, 369-377 [PubMed:2329164] [show Abstract] The high-performance liquid chromatographic assay described permitted a simple, rapid, sensitive, selective and precise quantitative determination of eugenol in body fluids (serum, urine and bile) without derivatization. Amounts in the range 0.02-100 micrograms of eugenol per millilitre of body fluid were determined with intra-assay coefficients of variation below 4% (3.72-1.13%). The short analysis time for each sample and the selectivity even at low concentrations made this assay suitable for pharmacokinetic studies. Eugenol undergoes a pronounced first-pass effect; in serum, unconjugated eugenol was not detected after an oral dose of 150 mg. The kinetics of eugenol conjugates were measured. More than 80% of the dose was excreted within 6 h after oral administration. |
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