Carvacrol has multiple targets. It is a potent activator of the human ion channels TRPV3 and TRPA1. It also acts as a neurotoxin, an antagonist of GABA, and an inhibitor of acetylcholinesterase (AchE). Furthermore, it downregulates Notch-1 and Jagged-1, and induces apoptosis.

In vitro, Carvacrol causes cell cycle arrest in the G0/G1 phase. It inhibits COX1 with an IC50 of 4000 nM and shows agonist activity at the human TRPA1 channel with an EC50 of 7000 nM. It also binds to human UDP glucuronosyltransferase 1A4.

In vivo, Carvacrol (20, 40, and 80 mg/kg, intragastric) reduces inflammation in rats by reducing serum pro-inflammatory molecules. Its antimicrobial properties make it effective against a range of bacterial and fungal pathogens.

The in vitro receptor binding assay for Carvacrol measures its activity on TRP channels. This is typically done using calcium flux assays in cells overexpressing TRPV3 or TRPA1, where the compound's ability to induce calcium influx is measured.

In vitro cell-based assays are performed in various cell lines to study its effects on cell cycle and apoptosis. Cells are treated with Carvacrol, and cell cycle distribution is analyzed by flow cytometry. Apoptosis is assessed by measuring markers like caspase activation.

In vivo activity is evaluated in animal models of inflammation, such as the rat model. Carvacrol is administered via intragastric gavage, and serum levels of pro-inflammatory cytokines are measured to assess its anti-inflammatory effect.

Absorption, Distribution and Excretion
Carvacrol appears to be slowly absorbed from the intestines in rabbits, as approximately 30% of a 1.5 g dose remained in the gastrointestinal tract 22 hours after administration, and approximately 25% was excreted in the urine. Carvacrol applied to the intact shaved abdominal skin of mice was not absorbed within 2 hours. Metabolism/Metabolites When fed to rabbits, the substituted monophenols thymol and carvacrol, present in plant essential oils, bind with glucuronic acid, acid, and sulfate. Carvacrol is metabolized by binding with glucuronic acid and sulfate. Known human metabolites of carvacrol include (2-methyl-5-prop-2-ylphenyl) hydrogen sulfate and (2S,3S,4S,5R)-3,4,5-trihydroxy-6-(2-methyl-5-prop-2-ylphenoxy)oxacyclohexane-2-carboxylic acid.
The pharmacokinetic properties of Carvacrol are not extensively detailed. As a volatile monoterpene, it is readily absorbed and distributed. It undergoes metabolism, primarily via glucuronidation, as indicated by its binding to UGT1A4.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Oregano (Origanum vulgare) leaves and oil contain carvacrol, thymol, eugenol, and rosmarinic acid. Oregano has been used to treat respiratory and gastrointestinal ailments and has antibacterial properties. Oregano oil has been recommended for treating nipple candidiasis during lactation; however, no clinical studies have confirmed its safety and efficacy. In Turkey, oregano has been used as a galactagogue. Currently, there is no data on whether oregano components are excreted into breast milk, or on the safety and efficacy of oregano for breastfeeding mothers or infants. Oregano and oregano oil are classified as "Generally Recognized As Safe" (GRAS) food ingredients by the U.S. Food and Drug Administration (FDA). Oregano is generally well tolerated, but gastrointestinal upset and allergic skin reactions have been reported in rare cases. Due to a lack of data, breastfeeding women should avoid consuming oregano in amounts exceeding those used as food flavorings. Dietary supplements do not require premarket approval from the U.S. Food and Drug Administration (FDA). Manufacturers are responsible for ensuring product safety but are not required to prove the safety and efficacy of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and the ingredients listed on the label often differ from the actual ingredients or amounts. Manufacturers may commission independent organizations to verify the quality of the product or its ingredients, but this does not guarantee the product's safety and efficacy. Given the above, clinical trial results for one product may not apply to other products. For more detailed information on dietary supplements, please visit other pages on the LactMed website.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.
Detailed toxicological data for Carvacrol is not available in standard research literature. As a natural compound with a long history of use as a food flavoring agent, it is generally recognized as safe (GRAS) at low concentrations. High doses may cause skin and eye irritation.

[1]. Carvacrol Induced Program Cell Death and Cell Cycle Arrest in Androgen-Independent Human Prostate Cancer Cells via Inhibition of Notch Signaling. Anticancer Agents Med Chem. 2019 Jul 31.

[2]. The bioactivity and toxicological actions of carvacrol. Crit Rev Food Sci Nutr. 2015;55(3):304-18.

[3]. Supplemental carvacrol can reduce the severity of inflammation by influencing the production of mediators of inflammation. Inflammation. 2015;38(3):1020-7.

Carvacrol is a phenolic compound and a natural monoterpene derivative of p-cymene. It inhibits bacterial growth and is therefore used as a food additive. Carvacrol is a potent activator of transient receptor potential V3 (TRPV3) and A1 (TRPA1) ion channels in the human body. It is used as a volatile oil component, flavoring agent, antibacterial agent, agrochemical, and TRPA1 channel agonist. Carvacrol belongs to the phenolic class of compounds, is a p-menthane monoterpene, and is also a plant-based antifungal agent. It is derived from the hydride of p-cymene. Carvacrol has been reported in Callistemon citrinus, Perilla frutescens, and several other organisms with relevant data. Carvacrol is a metabolite found or produced in Saccharomyces cerevisiae. See also: Oregano leaf oil (partial).
Carvacrol is a major component of essential oils and is used as a food flavoring ingredient and preservative, as well as a fragrance ingredient in cosmetics. Its antimicrobial properties make it a potential natural preservative. It is a promising lead compound for developing anti-inflammatory and analgesic drugs.

C10H14O

150.22

150.104

499-75-2

10364

Colorless to light yellow liquid

1.0±0.1 g/cm3

237.2±9.0 °C at 760 mmHg

3-4 °C(lit.)

106.7±0.0 °C

0.0±0.5 mmHg at 25°C

1.523

3.28

1

1

1

11

120

0

O([H])C1=C(C([H])([H])[H])C([H])=C([H])C(=C1[H])C([H])(C([H])([H])[H])C([H])([H])[H]

RECUKUPTGUEGMW-UHFFFAOYSA-N

InChI=1S/C10H14O/c1-7(2)9-5-4-8(3)10(11)6-9/h4-7,11H,1-3H3

2-methyl-5-propan-2-ylphenol

BRN-1860514; Carvacrol; Antioxine

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 (~665.69 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.64 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 (16.64 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 (16.64 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.)