Antibacterial; anthelmintic; antioxidant; Pesticide active substance; Flavoring Agents

O. Eugenol and gratissimum essential oil both work well to prevent H from changing into another species. contortus eggs, indicating possible application in the management of small ruminant gastrointestinal helminthiasis. Eugenol and essential oils had the strongest inhibitory impact at a concentration of 0.50% [1]. Eugenol inhibits the xanthine-xanthine oxidase system's ability to produce superoxide anions by 50% at a dose of 250 μM. Additionally, ethanol can reduce the synthesis of hydroxyl free radicals by 70%. The measurement of OH radical generation involves hydroxylating salicylate to 2,3-dihydroxybenzoate, and 46% of OH radical formation is inhibited by 250 μM eugenol [2]. Eugenol has antioxidant properties, but it also modulates the brain's monoaminergic pathways and HPA axis, which may help avoid gastrointestinal dysfunction similar to IBS that is brought on by RS. Like ondansetron, eugenol (50 mg/kg) decreased the rise in fecal particles brought on by RS by 80%. Eugenol affects the PFC and amygdala's serotonin pathway and reduces stress-induced increases in plasma corticosterone by 80%. Eugenol strengthens antioxidant defense mechanisms throughout the brain and reduces norepinephrine alterations brought on by stress [3].

Eugenol (33 mg/kg) given orally for two days considerably reduced knee edema, which persisted to do so at the conclusion of the treatment. After two days, rats with mycobacterial arthritis treated with eugenol showed a considerable reduction in paw swelling [4].

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Eugenol (50 mg/kg) reduced 80% of RS-induced increase in fecal pellets similar to that of ondansetron. Eugenol attenuated 80% of stress-induced increase in plasma corticosterone and modulated the serotonergic system in the PFC and amygdala. Eugenol attenuated stress-induced changes in norepinephrine and potentiated the antioxidant defense system in all brain regions. Conclusion: Eugenol protected against RS-induced development of IBS-like gastrointestinal dysfunction through modulation of HPA-axis and brain monoaminergic pathways apart from its antioxidant effect.[3]

The spice principles curcumin (from turmeric) and eugenol (from cloves) are good inhibitors of lipid peroxidation. Lipid peroxidation is known to be initiated by reactive oxygen species. The effect of curcumin and eugenol on the generation of reactive oxygen species in model systems were investigated. Both curcumin and eugenol inhibited superoxide anion generation in xanthine-xanthine oxidase system to an extent of 40% and 50% at concentrations of 75 microM and 250 microM respectively. Curcumin and eugenol also inhibited the generation of hydroxyl radicals (.OH) to an extent of 76% and 70% as measured by deoxyribose degradation. The .OH-radical formation measured by the hydroxylation of salicylate to 2,3-dihydroxy benzoate was inhibited to an extent of 66% and 46%, respectively, by curcumin and eugenol at 50 microM and 250 microM. These spice principles also prevented the oxidation of Fe2+ in Fentons reaction which generates .OH radicals.[2]

Preparation of tested materials[1]
The essential oil and eugenol were diluted in aqueous solution of Tween 20 (0.5%) in the following concentrations: 0.0625, 0.12, 0.25, 0.5 and 1.0% to be used in the egg hatch test.

Evaluation of anthelmintic activity[1]
The egg hatching test in vitro to evaluate the ovicidal activity was based on the method described by Coles et al. (1992). A suspension of 300 μl containing approximately 250 fresh eggs, recovered from feces of goats and sheep experimentally infected with H. contortus, were distributed and mixed with the same volume of the essential oil in different concentrations. These tests had three controls: distilled water, Tween 20 (0.5% aqueous solution) and thiabendazole (0.5% aqueous solution). The eggs were incubated for 48 h at room temperature. After 48 h, lugol was added to stop the egg hatch. All the eggs and first-stage larvae (L1) were counted. The test was repeated five times for each treatment and control. The values obtained were analyzed using ANOVA and the Duncan test at the 0.05% significance level.

Eugenol (12.5, 25, and 50 mg/kg), ondansetron (4.0 mg/kg, p.o.), and vehicle were administered to rats for 7 consecutive days before exposure to 1 h RS. One control group was not exposed to RS-induction. The effect of eugenol (50 mg/kg) with and without RS exposure was evaluated for mechanism of action and per se effect, respectively. The hypothalamic-pituitary-adrenal cortex (HPA)-axis function was evaluated by estimating the plasma corticosterone level. The levels of brain monoamines, namely serotonin, norepinephrine, dopamine, and their metabolites were estimated in stress-responsive regions such as hippocampus, hypothalamus, pre-frontal cortex (PFC), and amygdala. Oxidative damage and antioxidant defenses were also assessed in brain regions.[3]

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This study examined the effect of eugenol and ginger oil on severe chronic adjuvant arthritis in rats. Severe arthritis was induced in the right knee and right paw of male Sprague-Dawley rats by injecting 0.05 ml of a fine suspension of dead Mycobacterium tuberculosis bacilli in liquid paraffin (5 mg/ml). Eugenol (33 mg/kg) and ginger oil (33 mg/kg), given orally for 26 days, caused a significant suppression of both paw and joint swelling. These findings suggest that eugenol and ginger oil have potent antiinflammatory and/or antirheumatic properties.[4]

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The ovicidal activity of the essential oil of Ocimum gratissimum Linn. (Labideae) and its main component eugenol was evaluated against Haemonchus contortus, gastrointestinal parasite of small ruminants. The oil and eugenol were diluted in Tween 20 (0.5%) at five different concentrations. In the egg hatch test, H. contortus eggs were obtained from feces of goats experimentally infected. At 0.50% concentration, the essential oil and eugenol showed a maximum eclodibility inhibition. These results suggest a possible utilization of the essential oil of O. gratissimum as an aid to the control of gastrointestinal helmintosis of small ruminants.[1]

Absorption, Distribution and Excretion
Intraperitoneal injection of a single 450 mg/kg dose of (14)C methoxy labelled eugenol resulted in rapid distribution to all organs. Both ether- and water soluble materials were recovered from most tissues and excretions. Only 0.2-1.0% of the dose was eliminated as expired (14)CO2. Over 70% of a lethal dose of eugenol was recovered on death, from the urine of rabbits.
No penetration of mouse skin was demonstrated after dermal application of eugenol.

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Metabolism / Metabolites
Following ip injection of (14)C eugenol into rats, ... the presence of (14)CO2 in expired air indicated the demethylation of eugenol.
The metabolism and toxic effects of eugenol were studied in isolated rat hepatocytes. Incubation of hepatocytes with eugenol resulted in the formation of conjugates with sulfate, glucuronic acid and glutathione. The major metabolite formed was the glucuronic acid conjugate. Covalent binding to cellular protein was observed using (3)H eugenol. Loss of intracellular glutathione and cell death were also observed in these incubations. Concentrations of 1 mM eugenol caused a loss of over 90% of intracellular glutathione and resulted in approximately 85% cell death over a 5 hr incubation period. The loss of the majority of glutathione occurred prior to the onset of cell death (2 hr). The effects of eugenol were concentration dependent. The addition of 1 mM N-acetylcysteine to incubations containing 1 mM eugenol was able to completely prevent glutathione loss and cell death as well as inhibit the covalent binding of eugenol metabolites to protein. Conversely, pretreatment of hepatocytes with diethylmaleate to deplete intracellular glutathione increased the cytotoxic effects of eugenol. These results demonstrate that eugenol is actively metabolized in hepatocytes and suggest that the cytotoxic effects of eugenol are due to the formation of a reactive intermediate, possibly a quinone methide.
Two metabolites of eugenol, 3-piperidyl-1-(3'-methoxy-4'-hydroxyphenyl)-1-propanone and 3-pyrrolidinyl-1-(3'-methoxy-4'-hydroxyphenyl)-1-propanone, have been isolated from rat urine.
Epoxidation of eugenol by rat liver cell cultures has been reported. The dihydrodiol metabolite of eugenol has been isolated from liver homogenates and urine of rats pretreated with eugenol.
For more Metabolism/Metabolites (Complete) data for EUGENOL (9 total), please visit the HSDB record page.
Eugenol has known human metabolites that include Hydroxychavicol and (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-(2-methoxy-4-prop-2-enylphenoxy)oxane-2-carboxylic acid.

Hepatotoxicity
The low concentrations of eugenol and clove extracts used topically and in herbal products have not been convincingly linked to instances of liver injury, either in the form of serum enzyme elevations or clinically apparent liver injury. In high doses, however, eugenol appears to be a direct cytotoxin and several instances of severe acute liver and kidney injury have been reported after accidental overdose of eugenol containing herbal products, largely in children. Overdoses have been marked by the onset of agitation, decrease in consciousness and coma arising within hours on ingestion (10-30 mL of clove oil). There is typically an accompanying acidosis, respiratory depression and severe hypoglycemia requiring ventilation and intravenous glucose. Liver injury arises 12 to 24 hours after ingestion with marked elevations in serum aminotransferase levels and early coagulation abnormalities. Signs of hepatic failure arise rapidly, and jaundice can develop and deepen. The overall clinical presentation is typical of acute hepatic necrosis and similar to that of acetaminophen, iron or copper overdose. The liver injury generally worsens for several days but then rapidly improves and ultimately resolves within 1 to 3 weeks. Renal dysfunction may also occur but rarely requires intervention or dialysis. Long term injury or effects have not been described. Cases described in the literature have been in infants who swallowed clove oil being used by parents.
Likelihood score: C[H] (probable cause of clinically apparent liver injury in overdoses).

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Toxicity Data
LC50 > 2,580 mg/m3/4hr

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Interactions
Mice treated with eugenol (400-600 mg/kg, orally) in combination with an inhibitor of glutathione synthesis, buthionine sulfoximine (1 hr before eugenol, 4 mmol/kg, ip) developed hepatotoxicity characterized by increases in relative liver weight and serum glutamic-pyruvic transaminase, hepatic congestion, and centrilobular necrosis of hepatocytes. Eugenol (up to 600 mg/kg) alone produced no hepatotoxicity. Drug metabolism inhibitors such as carbon disulfide, methoxsalen, and piperonyl butoxide prevented or significantly reduced the hepatotoxic effect of eugenol given in combination with buthionine sulfoximine.
The present study was undertaken to evaluate the chemopreventive potential of eugenol alone and in combination with a chemotherapeutic agent such as gemcitabine. Eugenol showed dose-dependent selective cytotoxicity toward HeLa cells in comparison to normal cells, pointing to its safe cytotoxicity profile. A combination of eugenol and gemcitabine induced growth inhibition and apoptosis at lower concentrations, compared with the individual drugs. The analysis of the data using a combination index showed combination index values of <1 indicating strong synergistic interaction. The combination thus may enhance the efficacy of gemcitabine at lower doses and minimize the toxicity on normal cells. In addition, the expression analysis of genes involved in apoptosis and inflammation revealed significant downregulation of Bcl-2, COX-2, and IL-1beta on treatment with eugenol. Thus, the results suggest that eugenol exerts its anticancer activities via apoptosis induction and anti-inflammatory properties and also provide the first evidence demonstrating synergism between eugenol and gemcitabine, which may enhance the therapeutic index of prevention and/or treatment of cervical cancer.
The biochemical mechanisms underlying the increased toxicity of several plant essential oils (thymol, eugenol, pulegone, terpineol, and citronellal) against fourth instar of Aedes aegypti L. when exposed simultaneously with piperonyl butoxide (PBO) were examined. Whole body biotransformational enzyme activities including cytochrome P450-mediated oxidation (ethoxyresorufin O-dethylase (EROD)), glutathione S-transferase (GST), and beta-esterase activity were measured in control, essential oil-exposed only (single chemical), and essential oil + PBO (10 mg/liter) exposed larvae. At high concentrations, thymol, eugenol, pulegone, and citronellal alone reduced EROD activity by 5-25% 16 h postexposure. Terpineol at 10 mg/liter increased EROD activity by 5 +/- 1.8% over controls. The essential oils alone reduced GST activity by 3-20% but PBO exposure alone did not significantly affect the activity of any of the measured enzymes. All essential oils in combination with PBO reduced EROD activity by 58-76% and reduced GST activity by 3-85% at 16 hr postexposure. This study indicates a synergistic interaction between essential oils and PBO in inhibiting the cytochrome P450 and GST detoxification enzymes in Ae. aegypti.
... Swiss albino mice were administered different doses of eugenol (75,150 and 300 mg/kg) before exposure to 1.5 Gy of gamma radiation. The micronucleus test was carried out to determine the genetic damage in bone marrow. Our results demonstrated significant reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) with all three eugenol doses. Eugenol (150 mg/kg) was also tested against different doses of radiation (0.5, 1, 1.5, and 2 Gy) and was found to afford significant radioprotection. Reduction in the incidence of MnPCEs could be noticed up to 72 hr postirradiation (1.5 Gy). Moreover, the level of peroxidative damage and the specific activities of lactate dehydrogenase (LDH) and methylglyoxalase I (Gly I) were observed in the liver of mice treated with eugenol for seven days in comparison to untreated mice.
For more Interactions (Complete) data for EUGENOL (7 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Guinea pig oral 2130 mg/kg
LD50 Mouse ip 1109 mg/kg (7.5% eugenol in saline)
LD50 Rat oral 1930 mg/kg
LD50 Mouse intraperitoneal 500 mg/kg
For more Non-Human Toxicity Values (Complete) data for EUGENOL (6 total), please visit the HSDB record page.

[1]. Anthelmintic activity of essential oil of Ocimum gratissimum Linn. and eugenol against Haemonchus contortus. Vet Parasitol. 2002 Oct 16;109(1-2):59-63.

[2]. Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygenspecies and the oxidation of ferrous iron. Mol Cell Biochem. 1994 Aug 17;137(1):1-8.

[3]. Protective effect of eugenol against restraint stress-induced gastrointestinal dysfunction: Potential use in irritable bowel syndrome. Pharm Biol. 2015 Jul;53(7):968-74.

[4]. Suppressive effects of eugenol and ginger oil on arthritic rats. Pharmacology. 1994 Nov;49(5):314-8.

Therapeutic Uses
... Has been used as an antipyretic but it is relatively ineffective. /Eugenol/ has... been used in medicine for the study of mucous secretion /and/ gastric cytology, without gastric resection or gastroenterostomy. It has been shown to have anthelmintic properties. /SRP: Former use/
Nonprescription medicines for toothache commonly contain eugenol, and some products for canker-sore may do so also.
Eugenol is used as a component of several dental materials (e.g., dental cements, impression pastes and surgical pastes). Such products are principally combinations of zinc oxide and eugenol in varying ratios. They are reported to be widely used in dentistry as temporary filing materials, cavity liners for pulp protection, capping materials, temporary cementation of fixed protheses, impression materials and major ingredients of endodontic sealers. In addition, eugenol has been used in dentistry for disinfecting root canals.
Analgesic (dental)

C10H12O2

164.2011

164.083

C, 73.15; H, 7.37; O, 19.49

97-53-0

Eugenol-d3;1335401-17-6

3314

Colorless to light yellow liquid

1.1±0.1 g/cm3

255.0±0.0 °C at 760 mmHg

−12-−10 °C(lit.)

119.8±8.1 °C

0.0±0.5 mmHg at 25°C

1.536

2.2

1

2

3

12

145

0

OC1C(OC)=CC(CC=C)=CC=1

OC1=CC=C(CC=C)C=C1OC

InChI=1S/C10H12O2/c1-3-4-8-5-6-9(11)10(7-8)12-2/h3,5-7,11H,1,4H2,2H3

Phenol, 2-methoxy-4-(2-propen-1-yl)-; 2-methoxy-4-prop-2-enylphenol

4-Allyl-2-methoxyphenol; 4-Allylguaiacol; Eugenic acid; Allylguaiacol; p-Eugenol; Caryophyllic acid;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~609.01 mM)

Solubility in Formulation 1: ≥ 3.25 mg/mL (19.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 3.25 mg/mL (19.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 3.25 mg/mL (19.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)