Synonym name: 1,2-Dimethoxy-4-(2-propenyl)benzene; 4-Allylveratrole
Catalogue No.: BP0940
Cas No.: 93-15-2
Formula: C₁₁H₁₄O₂
Mol Weight: 178.231
Botanical Source: Present in many essential oils, e.g. nutmeg, mace and also many fruits, e.g. apple, banana, orange juice or peel, grapefruit, bilberry

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Methyleugenol (CAS No.: 93-15-2) is a naturally occurring phenylpropanoid compound, structurally an O-methylated eugenol derivative. As an important natural product, methyl eugenol is widely distributed in various aromatic plants, such as cinnamon, clove, basil, and lemongrass. Its unique chemical structure endows it with diverse biological activities, especially showing significant pharmacological potential in analgesia, anti-inflammation, antibacterial, and antioxidant properties. In recent years, with in-depth research into the pharmacological mechanisms of natural products, methyl eugenol has attracted attention due to its ability to regulate various pain-related targets, making it an important candidate for the development of natural analgesic drugs.

This paper aims to systematically review the chemical structure and physicochemical properties of methyl eugenol, its plant origin, and extraction methods, explore its pharmacological activity and mechanism of action in depth, evaluate its druggability and pharmacokinetic characteristics, and anticipate its potential value in clinical applications. By integrating existing research findings, it provides scientific basis and theoretical support for the further development and application of methyl eugenol.

Chemical structure and physicochemical properties

The chemical name of methyl eugenol is 1-methoxy-4-(2-propenyl)phenol, with a molecular formula C11H14O2 and a molecular weight of 178.2310. Its structural core is the phenylpropionyl framework, containing a methoxy-substituted benzene ring and an acrylene side chain. Methyl eugenol and eugenol have similar structures, but the difference is that the hydroxyl group on the benzene ring is methylated to methoxy, resulting in differences in its physicochemical properties and biological activity.

In terms of physicochemical properties, methyl eugenol has a LogP value of 2.9578, showing moderate lipid solubility, which facilitates lipid membrane penetration, especially high permeability of the blood-brain barrier (BBB), which provides a basis for pharmacological action in the central nervous system. Its topological polar surface area (TPSA) is 18.46 Ų, indicating low molecular polarity and further supporting its excellent membrane permeability. Low water solubility (0.1043 mg/mL) suggests limited solubility in the aqueous phase, which may affect its bioavailability. The hERG channel inhibition test results were negative, indicating a low risk of methyleugenol cardiotoxicity. The Ames test score was 0.6, indicating a low genotoxicity risk, but further long-term toxicological studies are needed for validation.

Plant Origins and Extraction Methods

Methyl eugenol is widely found in the essential oils of various aromatic plants, with main sources including:

• Clove (Syzygium aromaticum): Clove essential oil contains a relatively high amount of methyleugenol, which is one of its key components.
• Cinnamon (Cinnamomum spp.): Some essential oils of cinnamon species also contain a certain amount of methyl-eugenol.
• Basil (Ocimum basilicum): Its essential oil contains methyleugenol, which gives it a distinctive aroma and pharmacological activity.
• Lemongrass (Cymbopogon spp.): Methyleugenol has also been detected in lemongrass oil.

The extraction method mainly relies on distillation extraction techniques for plant essential oils. Steam distillation is the most commonly used process, which heats plant materials to release volatile components with the steam, which then condenses to obtain essential oils. Subsequently, gas chromatography-mass spectrometry (GC-MS) was used to qualitatively and quantitatively analyze the essential oil components to confirm the presence and content of methyleugenol.

In addition, supercritical CO2 extraction technology, due to its mild nature and solvent-free residue, is gradually being applied to methyl eugenol extraction, improving extraction efficiency and purity. Methods such as liquid-liquid extraction and column chromatography are commonly used for further purification.

Pharmacological activity research

Research on the pharmacological activity of methyl eugenol mainly focuses on its analgesic, anti-inflammatory, antibacterial, and antioxidant properties, with research on its analgesic effects being particularly in-depth.

Analgesic effect

Methyleugenol exhibits significant analgesic effects, involving various pain models including inflammatory pain, neuropathic pain, and acute pain. Both in vivo and in vitro experiments have shown that it can alleviate pain responses caused by heat, mechanical, and chemical stimuli. Its analgesic activity is closely related to the regulation of various molecular targets, covering ion channels, receptors, and enzymes.

Anti-inflammatory effects

Methyleugenol can inhibit the release of inflammatory mediators, reducing the expression of inflammatory factors such as prostaglandins (PGE2), tumor necrosis factor α (TNF-α), and interleukins (IL-1β, IL-6), thereby alleviating inflammatory responses. Its inhibitory effect on cyclooxygenases (COX-1/PTGS1 and COX-2/PTGS2) is an important component of its anti-inflammatory mechanism.

Antibacterial and antioxidant effects

Methyleugenol exhibits inhibitory activity against various bacteria and fungi, with particularly notable effects against Gram-positive bacteria. Additionally, it has the ability to scavenge free radicals and demonstrates strong antioxidant activity, helping to reduce tissue damage related to oxidative stress.

Mechanism of action and molecular targets

The analgesic effects of methyl eugenol involve various molecular targets, mainly including:

• TRPV1 (Transient Receptor Potential Vanillin Receptor 1): TRPV1 is a key ion channel in pain perception. Methyleugenol regulates TRPV1 activity, reduces calcium ion inflow, and inhibits pain signal transmission.
• TRPA1 (Transient Receptor Potential Vanillin Receptor A1): TRPA1 is involved in inflammation and chemical pain, and its regulation by methyl eugenol helps relieve related pain.
• CNR1 (Cannabinoid Receptor 1): CNR1 regulates pain perception in the central nervous system, and methyl eugenol may exert analgesic effects by activating or modulating this receptor.
• OPRD1, OPRM1, OPRK1 (δ, μ, κ opioid receptors): Methyleugenol modulates opioid receptors and enhances their analgesic effects, possibly suppressing pain signals by activating opioid receptor pathways.
• PTGS1 and PTGS2 (COX-1 and COX-2): Inhibit the activity of these two enzymes, reduce prostaglandin synthesis, and alleviate inflammation and pain.
• SLC6A4 (serotonin transporter): regulates serotonin levels, affects pain conduction and emotional state.
• DRD2 (dopamine D2 receptor): involved in central nervous system analgesic regulation.

Through multi-target synergistic effects, methyl eugenol can effectively relieve various types of pain with relatively low side effects.

Druggability evaluation and pharmacokinetics

The druggability evaluation of methyl eugenol shows it has good potential for drug development. The molecular weight is 178.23, meeting the Lipinski rule, with a LogP of about 2.96, indicating moderate lipophilicity and favorable cell membrane penetration. Low TPSA, supporting good oral absorption and blood-brain barrier permeability, suitable for central nervous system function.

Low water solubility may limit its bioavailability, so formulation technologies such as nanocarriers and liposomes are needed to improve solubility and stability. hERG channels have no inhibitory effects, reducing the risk of cardiotoxicity. Ames test results showed a low genotoxicity risk, but long-term toxicological safety still requires further validation.

Pharmacokinetics, methyleugenol is rapidly absorbed orally and widely distributed, especially accumulated in the central nervous system. Metabolism mainly occurs through oxidative and methylation pathways in the liver, and the safety of these metabolites still requires further research. Excretion is mainly through urine and feces.

Prospects and outlooks for clinical applications

Methyleugenol, as a naturally derived multi-target analgesic, has broad clinical application prospects. Its highly effective analgesic and anti-inflammatory properties give it potential therapeutic value in chronic pain, neuropathic pain, and inflammatory diseases. Compared to traditional opioids, methyleugenol may have lower addictiveness and side effects, making it suitable for long-term use.

Future research should focus on the following aspects:

1. Safety Evaluation: Systematic toxicological studies, including long-term toxicity, carcinogenicity, and reproductive toxicity assessments, ensure clinical application safety.
2. Pharmacokinetic optimization: Enhancing drug solubility and bioavailability through drug design and formulation improvements, optimizing administration regimens.
3. In-depth analysis of mechanism of action: Using molecular biology and pharmacological techniques, further elucidating its multi-target mechanism of action to guide clinical application.
4. Clinical trial implementation: designing reasonable clinical studies to verify efficacy and safety, promoting their transformation into clinical drugs.
5. Combination Medication Strategy: Explore combined use with other analgesics to achieve synergistic effects, reducing dosage and side effects.

In addition, methyl eugenol has potential in other fields such as antibacterial, antioxidant, and neuroprotective properties that are worth further exploring to expand its range of applications.

Conclusion

Methyl eugenol, as an important natural phenylpropanoid compound, demonstrates significant analgesic and anti-inflammatory potential due to its unique chemical structure and multi-target pharmacological activity. Its favorable druggability parameters and blood-brain barrier permeability provide favorable conditions for the development of central analgesic drugs. Although current research findings are encouraging, systematic safety evaluation and clinical validation are still needed to promote clinical application. In the future, with the development of natural product pharmacology and medicinal chemistry technologies, methyl eugenol is expected to become a new generation of safe and effective analgesic drugs, bringing new breakthroughs to pain management.