Identification

Name
Clove oil
Accession Number
DB11338
Type
Small Molecule
Groups
Approved, Nutraceutical
Description

Clove oil is obtained by extraction from the dried flower buds of the clove plant. Traditionally, it has been used as a flavouring spice in foods, or as a fragrance. It is also found in topical analgesics. Clove oil has shown to exert some antimicrobial activities. The antioxidant and antimicrobial activity of clove is higher than that of many fruits, vegetables, and other spices [2].

Clove is native of Indonesia but is now cultured in several parts of the world, including Brazil in the state of Bahia. This plant represents one of the richest source of phenolic compounds such as eugenol, eugenol acetate and gallic acid and has great potential for pharmaceutical, cosmetic, food and agricultural applications [2].

Interestingly, clove oil has been studied for its potential benefit in treating neuropathic pain, as well as vaginal candidiasis with promising results [4], [5].

The FDA categorizes clove oil as generally recognized as safe (GRAS) for use in dental cement or as a food additive [13].

Synonyms
  • Caryophylii floris aetheroleum
  • Caryophyllus aromaticus bud oil
  • Clove bud oil
  • Clove volatile oil
  • Ding xiang bud oil
  • Eugenia aromatica bud oil
  • Eugenia caryophyllata bud oil
  • Eugenia caryophyllus (clove) bud oil
  • Eugenia caryophyllus (clove) flower oil
  • Nelken oel
  • Syzygium aromaticum bud oil
  • Syzygium aromaticum oil
External IDs
Fema no. 2323
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Clove OilLiquidDentalD.C. Labs Limited1951-12-312003-07-11Canada
Clove OilLiquid100 %DentalStanley Pharmaceuticals, A Division Of Vita Health Products Inc.1965-12-312002-07-31Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Arhtri PlusClove oil (0.25 g/100g) + Eucalyptus oil (0.72 g/100g) + Menthol (2.5 g/100g)SprayTopicalDistributions Ar?Mes D`espagne Enr2014-10-30Not applicableUs
Dentalgar LiqClove oil (1.98 ml) + Benzocaine (54 mg) + Camphor (1.98 g) + Guaiacol (1.98 g) + Menthol (54 mg)LiquidDentalProduits Marc O (1987) Inc., Division Of Technilab Inc.1982-05-311999-09-17Canada
Denture Orajel GelClove oil (0.2 %) + Benzocaine (7.5 %) + Benzyl alcohol (1 %)GelBuccal; TopicalCommerce Pharmaceutics Inc.1997-12-172004-07-20Canada
Gouttes DentairesClove oil (6.6 ml) + Benzocaine (180 mg) + Camphor (6.6 g) + Guaiacol (6.6 g) + Menthol (180 mg)LiquidDentalLab Valmo EnregistrÉ, Division Of Technilab Inc.1983-12-312000-08-24Canada
New Skin Clear Liquid BandageClove oil (.8 %) + Oxyquinoline (1 %)LiquidTopicalMedtech Laboratories, Inc.1969-12-311998-07-08Canada
New Skin Clear Spray BandageClove oil (.8 %) + Oxyquinoline (1 %)AerosolTopicalMedtech Laboratories, Inc.1969-12-311998-07-08Canada
Categories
UNII
578389D6D0
CAS number
8000-34-8
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Clove oil is primarily indicated in conditions like colic, flatulence, and toothache [9].

Pharmacodynamics

Clove (Eugenia caryophyllata Thunb. [Myrtaceae]) essential oil (CEO) has been demonstrated to possess antimicrobial, antifungal, antiviral, antioxidant, anti-inflammatory, anti-histamine, and anticancer properties. However, few studies have focused on its topical use [2], [10].

Clove essential oil, used as an antiseptic in oral infections, inhibits gram-negative and gram-positive bacteria as well as yeast [1].

Mechanism of action

The chief constituent present in clove oil is the phenol "eugenol" which is present in amounts up to 85%. Clove oil acts as a germicide [9] to Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa [1].

Clove oil is thought to inhibit prostaglandin synthesis, thereby reducing painful symptoms [6].

Eugenol, the main constituent of clove oil is purported to have anticancer action. In one study, eugenol-treated HL-60 cells showed features of apoptosis including DNA fragmentation and formation of DNA ladders in agarose gel electrophoresis. It was observed that eugenol transduced the apoptotic signal via reactive oxygen species (ROS) generation, inducing mitochondrial permeability transition (MPT), decreasing anti-apoptotic protein bcl-2 level, inducing cytochrome c release to the cytosol, and subsequent apoptotic cell death. When taken together, the study showed that ROS plays a critical role in eugenol-induced apoptosis in HL-60, and this is the first report on the mechanism of the anticancer effect of eugenol [7].

TargetActionsOrganism
UVascular cell adhesion protein 1
antagonist
Human
UC-X-C motif chemokine 10Not AvailableHuman
UCollagen alpha-1(I) chainNot AvailableHuman
UGranulocyte-macrophage colony-stimulating factor receptor subunit alphaNot AvailableHuman
Absorption

Clove oil is rapidly absorbed through the skin and is used in patented systems for dermal drug delivery to enhance drug uptake from skin patch delivery systems [13].

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

In the rat, 20-30% of eugenol is metabolized to homovanillic acid and 4-hydroxy-3-methoxymandelic acid [10].

In a pharmacokinetic study in man, 95% of the ingested eugenol dose was recovered in the urine, most of which (greater than 99%) consisted of phenolic conjugates; 50% of the conjugated metabolites were eugenol-glucuronide and sulfate. Other metabolic routes observed were the epoxide-diol pathway, synthesis of a thiophenol and of a substituted propionic acid, allylic oxidation, and migration of the double bond [8].

Route of elimination

In a pharmacokinetic study, the metabolism of eugenol (the primary constituent of clove oil) was investigated in healthy male and female volunteers. It was quickly absorbed and metabolized after oral administration and was almost completely excreted in the urine within 24 hours of ingestion [8].

Half life

In a pharmacokinetic study, average half-life values of eugenol in plasma and blood were long (14.0 and 18.3 h, respectively), suggesting a potential accumulation of the drug following repeated administrations [4].

Clearance
Not Available
Toxicity

Acute oral toxicity (LD50): 2650 mg/kg [Rat] [MSDS].

Clove oil is considered safe in small quantities (< 1,500 ppm) as a food additive [13]. the lethal oral dose is 3.75 g per kg body weight in humans [13].

Contact with skin or soft tissue may cause transient irritation, contact dermatitis, inflammation of the lips, and inflammation or ulceration of the mouth. The eugenol present in clove oil may act as an irritant to skin and mucous membranes; it may also cause hypersensitivity and is reported to inhibit prostaglandin synthesis. Patients may become sensitive to clove oil [10].

After oral administration of 5-10 ml of clove oil in children below 2 years of age, life-threatening conditions were observed. Adverse effects included coma, acidosis, a generalized seizure, disordered blood clotting, and acute liver damage [13].

Overdose may lead to CNS depression, urinary abnormalities, anion-gap acidosis, deterioration of liver function, coma, seizure and low blood glucose levels. Treatment should be supportive and symptomatic; there have been reports in the literature that N-acetylcysteine has been successfully used as an antidote [10].

There are no epidemiological studies of potential adverse human health effects related to exposure to clove leave oil or eugenol from any human exposure scenarios. Nor are there any studies of agricultural use, either in workers or those with bystander exposure or other applications. There are no occupational exposure standards for clove leaf oil or eugenol including OSHA PEL (Permissible Exposure Limit) or AGIHA TLVs (Threshold Limit Value) in air [13].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Clove oil which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Clove oil which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Clove oil which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Clove oil which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Clove oil which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Clove oil which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Clove oil which could result in a higher serum level.
AcrivastineAcrivastine may decrease the excretion rate of Clove oil which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Clove oil which could result in a higher serum level.
AdefovirAdefovir may decrease the excretion rate of Clove oil which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Nunez L, Aquino MD: Microbicide activity of clove essential oil (Eugenia caryophyllata). Braz J Microbiol. 2012 Oct;43(4):1255-60. doi: 10.1590/S1517-83822012000400003. Epub 2012 Jun 1. [PubMed:24031950]
  2. Cortes-Rojas DF, de Souza CR, Oliveira WP: Clove (Syzygium aromaticum): a precious spice. Asian Pac J Trop Biomed. 2014 Feb;4(2):90-6. doi: 10.1016/S2221-1691(14)60215-X. [PubMed:25182278]
  3. Han X, Parker TL: Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts. Pharm Biol. 2017 Dec;55(1):1619-1622. doi: 10.1080/13880209.2017.1314513. [PubMed:28407719]
  4. Guenette SA, Ross A, Marier JF, Beaudry F, Vachon P: Pharmacokinetics of eugenol and its effects on thermal hypersensitivity in rats. Eur J Pharmacol. 2007 May 7;562(1-2):60-7. doi: 10.1016/j.ejphar.2007.01.044. Epub 2007 Feb 1. [PubMed:17321520]
  5. Ahmad N, Alam MK, Shehbaz A, Khan A, Mannan A, Hakim SR, Bisht D, Owais M: Antimicrobial activity of clove oil and its potential in the treatment of vaginal candidiasis. J Drug Target. 2005 Dec;13(10):555-61. doi: 10.1080/10611860500422958 . [PubMed:16390816]
  6. Pongprayoon U, Baeckstrom P, Jacobsson U, Lindstrom M, Bohlin L: Compounds inhibiting prostaglandin synthesis isolated from Ipomoea pes-caprae. Planta Med. 1991 Dec;57(6):515-8. doi: 10.1055/s-2006-960196. [PubMed:1818340]
  7. Yoo CB, Han KT, Cho KS, Ha J, Park HJ, Nam JH, Kil UH, Lee KT: Eugenol isolated from the essential oil of Eugenia caryophyllata induces a reactive oxygen species-mediated apoptosis in HL-60 human promyelocytic leukemia cells. Cancer Lett. 2005 Jul 8;225(1):41-52. doi: 10.1016/j.canlet.2004.11.018. Epub 2004 Dec 15. [PubMed:15922856]
  8. Fischer IU, von Unruh GE, Dengler HJ: The metabolism of eugenol in man. Xenobiotica. 1990 Feb;20(2):209-22. [PubMed:2333717]
  9. Drug Infosys: Clove Oil [Link]
  10. Medicines UK Document, Clove Oil [Link]
  11. Eugenol Overview [Link]
  12. Clove oil, FDA Document [File]
  13. Chapter 6- Eugenol [File]
External Links
PubChem Substance
347911190
ChEMBL
CHEMBL2108247
Wikipedia
Clove_oil
MSDS
Download (47.3 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SprayTopical
LiquidDental
LiquidDental100 %
LiquidDental
GelBuccal; Topical
LiquidTopical
AerosolTopical
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
boiling point (°C)250MSDS
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Primary amine oxidase activity
Specific Function
Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with integrin alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both adhesion and si...
Gene Name
VCAM1
Uniprot ID
P19320
Uniprot Name
Vascular cell adhesion protein 1
Molecular Weight
81275.43 Da
References
  1. Han X, Parker TL: Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts. Pharm Biol. 2017 Dec;55(1):1619-1622. doi: 10.1080/13880209.2017.1314513. [PubMed:28407719]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor binding
Specific Function
Chemotactic for monocytes and T-lymphocytes. Binds to CXCR3.
Gene Name
CXCL10
Uniprot ID
P02778
Uniprot Name
C-X-C motif chemokine 10
Molecular Weight
10880.915 Da
References
  1. Han X, Parker TL: Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts. Pharm Biol. 2017 Dec;55(1):1619-1622. doi: 10.1080/13880209.2017.1314513. [PubMed:28407719]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Platelet-derived growth factor binding
Specific Function
Type I collagen is a member of group I collagen (fibrillar forming collagen).
Gene Name
COL1A1
Uniprot ID
P02452
Uniprot Name
Collagen alpha-1(I) chain
Molecular Weight
138941.105 Da
References
  1. Han X, Parker TL: Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts. Pharm Biol. 2017 Dec;55(1):1619-1622. doi: 10.1080/13880209.2017.1314513. [PubMed:28407719]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor activity
Specific Function
Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells.
Gene Name
CSF2RA
Uniprot ID
P15509
Uniprot Name
Granulocyte-macrophage colony-stimulating factor receptor subunit alpha
Molecular Weight
46206.185 Da
References
  1. Han X, Parker TL: Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts. Pharm Biol. 2017 Dec;55(1):1619-1622. doi: 10.1080/13880209.2017.1314513. [PubMed:28407719]

Drug created on December 03, 2015 09:52 / Updated on November 02, 2018 07:09