Many Gram-positive and Gram-negative bacteria, such as Salmonella type B, Bacillus licheniformis, Micrococcus luteus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, are susceptible to isoeugenol's antibacterial action[1].

Absorption, Distribution and Excretion
Following a single oral dose of (14) C-isoeugenol (156 mg/kg, 50 uCi/kg), over 85% of the administered dose was excreted in the urine primarily as sulfate or glucuronide metabolites within 72 hours. Approximately 10% was recovered in feces, and less than 0.1% was recovered as CO₂ or exhaled organic matter. Parent isoeugenol was not detected in blood at any of the analytical time points. Following intravenous administration (15.6 mg/kg, 100 uCi/kg), isoeugenol rapidly disappeared from the blood. The half-life was 12 minutes, and the clearance rate was 1.9 L/min/kg. Excretion characteristics were similar to those of oral administration. Less than 0.25% of the administered dose remained in selected tissues within 72 hours after oral or intravenous administration. These results indicate that isoeugenol is rapidly metabolized and primarily excreted in the urine as a phase II conjugate of the parent compound.

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Metabolism/Metabolites
Following a single oral dose of (14)C-isoeugenol (156 mg/kg, 50 uCi/kg), over 85% of the administered dose was excreted in the urine primarily as sulfate or glucuronide metabolites within 72 hours. Approximately 10% was recovered in feces, and less than 0.1% was recovered as CO₂ or exhaled organic matter. Parent isoeugenol was not detected in the blood at any of the analytical time points. Following intravenous administration of isoeugenol (15.6 mg/kg, 100 μCi/kg), isoeugenol was rapidly cleared from the blood. The half-life was 12 minutes, and the clearance rate (Cl(s)) was 1.9 L/min/kg. Its excretion characteristics were similar to those of oral administration. The total radioactivity remaining in specific tissues within 72 hours after oral or intravenous administration was less than 0.25% of the administered dose. These findings indicate that isoeugenol is rapidly metabolized, primarily excreted in the urine as a phase II conjugate of the parent compound. Known metabolites of trans-isoeugenol include trans-isoeugenol-O-glucuronide. The half-life of isoeugenol (15.6 mg/kg, 100 uCi/kg) after intravenous injection is 12 minutes.

Non-Human Toxicity Values

Oral LD50 in rats: 1560 mg/kg
Oral LD50 in guinea pigs: 1410 mg/kg

[1]. Isoeugenol has a non-disruptive detergent-like mechanism of action.Front Microbiol. 2015 Jul 28;6:754.

Isoeugenol is a pale yellow, oily liquid with a spicy clove-like odor. Its freezing point is -10°C (14°F). Its density is 1.08 g/cm³. It is found in ylang-ylang essential oil and other essential oils. Isoeugenol is a phenylpropanoid compound, an isomer of eugenol in which the allyl substituent is replaced by a propenyl group. It is a sensitizer and allergen. It belongs to the phenylpropanoid and alkenylbenzene classes. Its function is similar to guaiacol. Isoeugenol is a commonly used fragrance ingredient added to many commercially available products and is naturally found in the essential oils of plants such as ylang-ylang. It is also an important skin sensitizer and allergen; therefore, according to guidelines issued by the fragrance industry, its content has been limited to 200 ppm since 1998. Allergic reactions to isoeugenol can be identified through patch testing. Isoeugenol has been reported to be found in perilla, datura, and other organisms with relevant data. Isoeugenol is a clear to pale yellow oily liquid extracted from certain essential oils, especially clove oil and cinnamon oil. It is slightly soluble in water and readily soluble in organic solvents. It has a pungent clove odor and taste. Isoeugenol can be prepared by heating eugenol. Eugenol is used in perfumes, flavorings, essential oils, and pharmaceuticals (topical disinfectants and analgesics). It is used to produce isoeugenol, which in turn is used to manufacture vanillin. Eugenol derivatives, or more broadly, methoxyphenol derivatives, are used in perfumes and flavorings. They are used to formulate insect attractants and UV absorbers, analgesics, bactericides, and preservatives. They are also used to manufacture stabilizers and antioxidants for plastics and rubber. Isoeugenol is used in the manufacture of perfumes, flavorings, essential oils (odor description: clove, spicy, sweet, woody), and pharmaceuticals (topical disinfectants and analgesics), and vanillin is also used for this purpose. (A7915).
E-4-propenyl-2-methoxyphenol is a metabolite found or produced in Saccharomyces cerevisiae.
See also: cis-isoeugenol (note moved to).
Drug Indications
Isoeugenol is FDA approved for use in allergic skin patch testing for the auxiliary diagnosis of allergic contact dermatitis (ACD) in individuals aged 6 years and older.
Mechanism of Action
/Researchers/Previously demonstrated in the human promyelocytic cell line THP-1 that, except for the pre-hapten isoeugenol, all tested allergens induced dose-dependent release of interleukin-8 (IL-8). This study aimed to investigate whether this aberrant behavior is regulated by the AU-rich binding protein HuR and t-tetraproline protein (TTP) or the downstream molecule cytokine signaling inhibitory factor (SOCS)-3. Contact allergens isoeugenol, diethyl maleate (DEM), and 2,4-dinitrochlorobenzene (DNCB), along with the irritant salicylic acid, were used as reference compounds. The concentrations of all chemicals used were designed to reduce cell viability by 20% (assessed by propidium iodide staining), specifically: isoeugenol 100 μg/mL (0.61 mM), DEM 100 μg/mL (0.58 mM), DNCB 3 μg/mL (14.8 μM), and salicylic acid 250 μg/mL (1.81 mM). Time-course assays of IL-8 mRNA expression and assessment of IL-8 mRNA half-life showed decreased IL-8 mRNA stability in isoeugenol-treated cells. We found that the combination and regulation of HuR and TTP after allergen exposure led to different changes in IL-8 mRNA half-life and release. Increased TTP expression in isoeugenol-treated THP-1 cells resulted in IL-8 mRNA instability, which could explain the loss of IL-8 release. Conversely, while the potent allergen DNCB induced HuR expression, it failed to upregulate TTP, leading to a prolonged IL-8 mRNA half-life and increased protein release. SOCS-3 was induced only in cells treated with isoeugenol; however, its regulation did not rescue the loss of IL-8 release, indicating that SOCS-3 is unlikely to be involved in IL-8 production. Finally, the destabilizing effect of isoeugenol on IL-8 mRNA expression and its inhibitory effect on SOCS-3 expression led to an anti-inflammatory effect, as evidenced by isoeugenol's ability to regulate LPS- or iomycin-induced cytokine release. Isoeugenol and its structural analogue eugenol inhibited the lymphocyte proliferation response stimulated by concanavalin A in B6C3F1 mouse spleen cell cultures. Isoeugenol inhibited IL-2 mRNA expression and protein secretion in B6C3F1 mouse spleen cells and EL4.IL-2 mouse T cells induced by phorbol 12-myristate 13-acetate (PMA) and iomycin (Io), as confirmed by real-time RT-PCR and ELISA, respectively. To further elucidate the inhibitory mechanism of isoeugenol at the transcriptional level, we used electrophoretic mobility shift analysis to detect the DNA-binding activity of IL-2 transcription factors. The results showed that isoeugenol reduced the binding activity of NF-AT and NF-κB in PMA/Io-stimulated EL4.IL-2 cells, but had no significant effect on the binding activity of AP-1 or Oct. Western blot analysis indicated that isoeugenol also reduced the nuclear translocation of cytoplasmic NF-AT and NF-κB. These results suggest that isoeugenol inhibits IL-2 production by reducing IL-2 mRNA expression, and that this inhibition is at least partially mediated by downregulating NF-AT and NF-κB. Eugenol and isoeugenol are phenolic derivatives naturally found in various fragrance essential oils and are commonly used as flavorings. Recent data suggest that the growth-inhibiting effects of these substances on keratinocytes may be mediated through aryl hydrocarbon receptor (AhR) interactions. This study investigated the effects of eugenol and isoeugenol on the intracellular localization of AhR, expression of AhR target genes, AhR-dependent cell cycle regulation, and proliferation in HaCaT cells. Both compounds rapidly and significantly promoted AhR translocation to the nucleus, induced the expression of AhR target genes cytochrome P-450 1A1 (CYP1A1) and AhR repressor (AhRR), and inhibited HaCaT cell proliferation. Among G1 phase cell cycle-related proteins, the levels of retinoblastoma protein (RB) and cyclin-dependent kinase (CDK) 6, which are known to interact with AhR, were decreased by eugenol and isoeugenol, while the homeostatic levels of CDK2 and CDK4 remained unaffected. The protein level of the CDK inhibitor (CKI) p27 (KIP1) is known to be AhR-dependently regulated; its protein level increased after treatment with both substances. In conclusion, the data indicate that the antiproliferative effects of eugenol and isoeugenol in HaCaT cells are mediated by AhR… We analyzed the effects of eugenol compounds on nitric oxide (NO) production in RAW264.7 macrophages and linked this to the anti-inflammatory effects of these compounds. Both eugenol and isoeugenol inhibited lipopolysaccharide (LPS)-dependent NO production by suppressing the synthesis of inducible nitric oxide synthase (iNOS) protein. Isoeugenol showed the strongest inhibitory effect, while eugenol showed a weaker inhibitory effect. Isoeugenol also significantly inhibited LPS-dependent cyclooxygenase-2 (COX-2) protein expression, while eugenol showed a weaker inhibitory effect. The anti-inflammatory effects of eugenol compounds may be related to their inhibition of the pro-inflammatory mediators NO production and COX-2 expression. For more complete data on the mechanisms of action of isoeugenols (a total of 8 compounds), please visit the HSDB record page.

C10H12O2

164.2011

164.083

97-54-1

63661-65-4 (sodium salt)

853433

Colorless to light yellow liquid

1.1±0.1 g/cm3

266.6±20.0 °C at 760 mmHg

-10 °C

122.9±6.7 °C

0.0±0.6 mmHg at 25°C

1.578

2.45

1

2

2

12

154

0

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

BJIOGJUNALELMI-ONEGZZNKSA-N

InChI=1S/C10H12O2/c1-3-4-8-5-6-9(11)10(7-8)12-2/h3-7,11H,1-2H3/b4-3+

2-methoxy-4-[(E)-prop-1-enyl]phenol

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: ≥ 2.5 mg/mL (15.23 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (15.23 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 25.0 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: ≥ 2.5 mg/mL (15.23 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 25.0 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.)