Estragole acts on peripheral nerves to decrease neuronal excitability. The specific molecular target(s) (e.g., ion channels) are not identified in this study [1].

Estragole induced a dose-dependent and reversible blockade of the compound action potential (CAP) in isolated rat sciatic nerves.
At 0.6 mM, Estragole had no significant effect on CAP peak-to-peak amplitude (PPA) or conduction velocity after 180 minutes of exposure [1].
At 2.0 mM, Estragole significantly reduced PPA to 85.6 ± 3.96% of control by the end of 180-min exposure. Conduction velocity was also reduced [1].
At 4.0 mM, Estragole significantly reduced PPA to 49.3 ± 6.21% of control, reduced conduction velocity to 77.7 ± 3.84% of control, increased chronaxy (the pulse width at twice rheobase) to 125.9 ± 10.43% of control, and increased rheobase (threshold stimulus voltage) to 116.7 ± 4.59% of control after 180 minutes [1].
At 6.0 mM, Estragole significantly reduced PPA to 13.04 ± 1.80% of control after 180 minutes [1].
All effects developed slowly over tens of minutes and were fully reversible after a 300-minute wash-out period [1].

Absorption, Distribution and Excretion
In non-inbred male CD-1 mice, approximately 20% of the estrogen dose (a naturally occurring flavoring agent) is excreted in the urine as a conjugate of 1'-hydroxyestrogens (presumably glucuronide). ... Metabolism/Metabolites This study investigated individual variability in the levels of 1'-hydroxyestrogens, a proximal oncogenic metabolite of estrogen, in the liver. This variability is due to differences in two key metabolic reactions involved in the formation and detoxification of this metabolite: 1'-hydroxylation of estrogen and oxidation of 1'-hydroxyestrogens. The production of 1'-hydroxyestrogens is primarily catalyzed by P450 1A2, 2A6, and 2E1, and our results support the view that the oxidation of 1'-hydroxyestrogens is catalyzed by 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2). First, a physiologically based biokinetic (PBBK) model was established for 14 participants. The results showed a 1.8-fold inter-individual variability in the area under the curve (AUC) of 1'-hydroxyestrogens (HSA) concentration-time in the liver. The difference in 17β-HSD2 activity regarding HSA oxidation had a greater impact than the difference in P450 enzyme activity. Second, Monte Carlo simulations were used to assess the potential variability in HSA liver levels across the entire population. This analysis was used to derive a chemical substance-specific adjustment factor (CSAF), defined as the 99th percentile of the predicted distribution of HSA AUC in the liver divided by the 50th percentile. The estimated CSAF ranged from 1.6 to 4.0, depending on the degree of variability in HSA oxidation considered. Comparing the CSAF to the default uncertainty factor of 3.16, used to explain human biokinetic variability, indicated that the default uncertainty factor was sufficient to protect 99% of the population. The extent to which the herbal estrogen component is bioactivated to its final carcinogenic metabolite, 1'-sulfonyl estrogens, depends on the relative levels of bioactivation and detoxification pathways. This study investigated the metabolic kinetics of estrogen and its proximal carcinogenic metabolite, 1'-hydroxyestrogens, in humans under incubation conditions with relevant tissue components. Based on the obtained kinetic data, a physiological biokinetic (PBBK) model of estrogen in humans was constructed to predict the degree of bioactivation and detoxification at different doses of estrogen. The predictions from this model were then compared with previous predictions based on a male rat estrogen PBBK model to assess whether there are species differences in metabolic activation. The results showed that the secondary metabolic pathway of 1'-hydroxyestrogens in rats—the generation of 1'-oxoestrogens—is the main detoxification pathway of 1'-hydroxyestrogens in humans. Because the 1'-hydroxyestrone oxidation pathway is highly active in the human liver, the predicted production of 1'-sulfonoxyestrone remains relatively small across species. Although the production of its precursor, 1'-hydroxyestrone, is expected to be four times higher in humans than in male rats, the predicted production of 1'-sulfonoxyestrone in humans is still twice that in male rats. In summary, the conclusion is that despite significant differences in the relative extent of different metabolic pathways between humans and male rats, species differences have little impact on the final bioactivation of estrogen to 1'-sulfonoxyestrone.
1. This study used [methoxy-(14)C]-labeled compounds to investigate the metabolic pathways of natural food flavoring trans-anisole and estrogen and their synthetic homologues on propylanisole in human volunteers. The doses used were close to dietary intake, at 1 mg, 100 μg, and 100 μg, respectively. 2. In all cases, the primary elimination pathway of ¹⁴C was via urine and exhaled gases, resulting in the excretion of ¹⁴C as CO₂. 3. Urinary metabolites were separated using solvent extraction, thin-layer chromatography, and high-performance liquid chromatography, and characterized by chromatographic migration comparison with standards and radioisotope dilution. Nine ¹⁴C urinary metabolites were detected after administration of trans-anisole, four after administration of p-propyl anisole, and five after administration of estrogen. All of these metabolites were side-chain oxidation products. 4. The primary metabolites of p-propyl anisole were 4-methoxyhippuric acid (12%), 1-(4'-methoxyphenyl)prop-1-ol (2%), and 1-(4'-methoxyphenyl)prop-2-ol (8%). 5. The major metabolite of trans-anetinoside is 4-methoxyhippuric acid (56% of the dose), accompanied by small amounts of two isomers of 1-(4'-methoxyphenyl)propane-1,2-diol (3% in total). 6. Following estrogen administration, two volunteers excreted 0.2% and 0.4% of the dose, respectively, as 1'-hydroxyestrogens. 7. Human metabolic data are discussed, with reference to the metabolic distribution of these compounds in mice and rats (species commonly used for safety assessments).
The metabolism of the potent carcinogen estrogen after consumption of anise tea in humans was investigated by analyzing metabolites in plasma and urine. Stable isotope dilution analysis based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed that the 1'-hydroxylation of estrogen occurred very rapidly, with the concentration of bound 1'-hydroxyestrogens in urine peaking at 1.5 hours and becoming undetectable after 10 hours. Besides the generation of less than 0.41% of conjugated 1'-hydroxyestrogens in the administered estrogen dose, the proportion of allylphenol, a further metabolite of estrogen, was even higher (17%). Both metabolites were also detected in plasma within 0.75–2.5 hours after consuming anise tea. Conversely, the estrogen concentrations in these samples did not exceed the detection limit. This suggests that excessive amounts of trans-anetinoside, the main aroma component of anise, do not primarily interfere with estrogen metabolism, but its influence on the quantitative composition of metabolites cannot be ruled out. Due to its high reactivity and instability, the presence of estrogen sulfate conjugates could not be confirmed.
For more complete data on the metabolism/metabolites of 1-methoxy-4-(2-propenyl)benzene (11 in total), please visit the HSDB record page.

[1]. Effects of estragole on the compound action potential of the rat sciatic nerve. Braz J Med Biol Res. 2004 Aug;37(8):1193-8.

[2]. Anti-Toxoplasma Activity of Estragole and Thymol in Murine Models of Congenital and Noncongenital Toxoplasmosis. J Parasitol. 2016 Jun;102(3):369-76.

According to an independent committee of scientific and health experts, estrogen may be carcinogenic. Estrogen is a colorless liquid with an anise-like odor and is insoluble in water. It is isolated from the peel and estrogen oil of avocado (Persea gratissima Grath.). It is also found in Russian anise oil, basil oil, anise turpentine oil, tarragon oil, and anise bark oil. (NTP, 1992) Estrogen is a phenylpropanoid compound, a compound in which the hydroxyl group of chavicol is replaced by a methoxy group. It has various uses, including as a flavoring agent, insect attractant, plant metabolite, genotoxin, and carcinogen. It is an alkenylbenzene, monomethoxybenzene, and phenylpropanoid compound. It is functionally related to chavicol. Estrogen has been reported in lemongrass, perilla, and other organisms with relevant data. See also: anise oil (partial); tarragon (note moved to).

---

Mechanism of Action
Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that regulates cellular signaling pathways. Its inactivation is correlated with tumor malignancy, likely due to its influence on cell differentiation and malignant cell transformation. Therefore, PP2A is considered a promising target for cancer therapy. In our previous study of the liver carcinogen estrogen (ES), cell proliferation may be necessary for the conversion of ES-specific DNA adducts into mutations. To investigate the triggering factors of cell proliferation, we administered ES to gpt delta rats via gavage at doses of 3, 30, and 300 mg/kg/day for 4 consecutive weeks. The results showed that ES-induced cell proliferation and gene mutations were observed only in the high-dose group, while the production of ES-specific DNA adducts was dose-dependent. Western blot analysis revealed activation of the Akt and ERK pathways, but upstream regulators such as c-Raf, PKC, and PI3K were not activated. Furthermore, we found phosphorylation at the Tyr307 site of the PP2A C subunit and phosphorylation at the Src site. Overall data indicate that high-dose ES may promote cell cycle progression by activating Akt and ERK pathways, leading to PP2A inactivation. Based on γ-H2AX immunohistochemistry and Western blot analysis of Rad51 protein, we found large fragment deletion mutations in the mutation spectrum, which may be caused by DNA double-strand breaks. Therefore, PP2A inactivation is likely to lead to the acceleration and exacerbation of gene mutations. We conclude that PP2A may be involved in the early stage of chemical carcinogenesis, suggesting that PP2A may become a molecular target for primary cancer prevention.

---

Estrogen (methylpiperol) is a volatile terpene ether and a major component of essential oils from many plants (e.g., basil, fennel, tarragon), which are widely used in folk medicine and aromatherapy[1].
This study is the first to demonstrate that estrogen acts on peripheral nerves and reversibly inhibits parameters related to excitability (compound action potential amplitude, conduction velocity, duration, threshold current). This local anesthetic-like activity can be observed in the millimolecular concentration range[1].
This study did not investigate the mechanism of reduced excitability, but suggested that it may be related to changes in passive membrane properties, voltage-dependent sodium conductance, or geometric factors[1].
It is claimed that the effective concentration range of Estragole for nerve blockade (2-6 mM) is similar to that of classic local anesthetics such as procaine and lidocaine. The authors noted that under their experimental conditions, Estragole appeared to completely block all components of the complex action potential (CAP), and its blocking effect on some sensory fiber components was similar to, or even more thorough than, that of lidocaine[1].
This study cited previous research showing that Estragole has sedative and anticonvulsant activity, which is related to its effects on the central nervous system[1].

C10H12O

148.2017

148.088

140-67-0

8815

Colorless to light yellow liquid

0.9±0.1 g/cm3

216.0±0.0 °C at 760 mmHg

81.1±0.0 °C

0.2±0.4 mmHg at 25°C

1.505

3.15

0

1

3

11

112

0

O(C([H])([H])[H])C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])=C([H])[H]

ZFMSMUAANRJZFM-UHFFFAOYSA-N

InChI=1S/C10H12O/c1-3-4-9-5-7-10(11-2)8-6-9/h3,5-8H,1,4H2,2H3

1-methoxy-4-prop-2-enylbenzene

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 (~674.76 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.87 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.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (16.87 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (16.87 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.

---

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