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Synonym name: Levomenthol; (-)-Menthol;
Catalogue No.: BP0880
Cas No.: 2216-51-5
Formula: C10H20O
Mol Weight: 156.269
Botanical Source: Present in large amts. in Mentha piperita (peppermint) oil, also in other Mentha spp., Artemisia spp., Glechoma hederacea and others
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.
HPLC of L-Menthol
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
20.2300
3.2688
3.2688
.5241
6.2669
14.1712
High
71.8096
3.3527
Yes
No
No
No
No
No
0.0
No
No
No
No
L-menthol (L-menthol), CAS number 2216-51-5, is a naturally occurring monoterpenoid alcohol compound with a stereochemical configuration of (1R, 2S, 5R), and is the main natural enantiomer of menthol. As one of the most abundant active ingredients in the mint plant, L-menthol has long been widely used in medicine, food, cosmetics, and other fields due to its unique cooling sensation and diverse pharmacological activities. In recent years, with in-depth research into its molecular mechanisms, L-menthol has shown significant therapeutic potential in various physiological and pathological processes such as analgesia, antispasmodic, and anti-itch, attracting widespread attention especially in the field of pain management.
This review aims to systematically summarize the chemical structure and physicochemical properties of L-menthol, its plant origins and extraction methods, with a focus on evaluating its pharmacological activity and mechanism of action. By combining its medicinal parameters and pharmacokinetic characteristics, it explores its clinical application prospects and future research directions, providing a reference for researchers in the field of natural product pharmacology.
The chemical name of L-menthol is (-)-menthol-3-alcohol, with a molecular formula C10H20O and a molecular weight of 156.2690. Its structural feature is a monocyclic terpene backbone containing a hydroxyl (-OH) functional group, endowing it with hydrophilicity and the ability to interact with biological targets. The stereochemical configuration is (1R, 2S, 5R), which significantly differs in bioactivity from the enantiomer (+)-menthol.
In terms of physicochemical properties, the LogP value of L-menthol is 3.2688, indicating moderate lipid solubility and facilitating penetration of biofilms. The topological pole surface area (TPSA) is 20.23 Ų. The relatively low polar surface area helps with its blood-brain barrier (BBB) penetration capability, and experimental data also indicate high BBB permeability. Water solubility is 0.5241 mg/mL, classifying it as a low-solubility compound, but sufficient to support its bioavailability in the body. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0, indicating no significant gene mutation induction and relatively high safety.
L-menthol is mainly found in the Lamiaceae family plant genus Mentha, with abundant content in peppermint (Mentha piperita) and green spearmint (Mentha spicata). Mint plants are widely cultivated for their refreshing aroma and medicinal value, with L-menthol being the main component of their volatile oils.
Traditional extraction methods include steam distillation and organic solvent extraction. Due to its simplicity and low cost, steam distillation remains the main method for industrial-scale extraction of L-menthol. In recent years, supercritical CO2 extraction technology has gradually become the preferred method for extracting L-menthol due to its high selectivity, absence of solvent residues, and environmental advantages. In addition, microwave-assisted extraction and ultrasound-assisted extraction technologies are also applied to improve extraction efficiency and purity.
After extraction, purity analysis and enantiomer identification are often performed through fractionation and chromatography techniques (such as GC-MS for gas chromatography-mass spectrometry) to ensure the acquisition of high-purity L-menthol to meet medicinal needs.
L-menthol has various pharmacological activities, mainly including analgesic, antispasmodic, and anti-itch effects. It also exhibits potential activities such as anti-inflammatory, antibacterial, and neuromodulatory.
Analgesia is one of the most significant pharmacological effects of L-menthol. In vivo and in vitro experiments have shown that L-menthol can effectively alleviate inflammatory and neuropathic pain, with mechanisms involving regulation of multiple ion channels and receptors. Its analgesic effect is especially pronounced when applied locally, commonly used to relieve muscle pain, headaches, and neuralgia.
L-menthol has antispasmodic effects on smooth muscle, which can relieve spasms in the gastrointestinal and respiratory tract smooth muscles. It regulates calcium channels and neurotransmitter release, reducing muscle spasms and related discomfort.
The anti-itch effect of L-menthol is mainly reflected in local application on the skin, helping to relieve itching caused by various factors. It alleviates skin itching by activating cold receptors and inhibiting the release of inflammatory mediators.
Some studies report that L-menthol has anti-inflammatory activity, can inhibit the production and release of inflammatory factors, and reduce inflammatory responses. In addition, L-menthol also shows certain potential in antibacterial, antioxidant, and neuroprotective aspects, warranting further in-depth study.
The pharmacological effects of L-menthol are mainly achieved through multi-target and multi-pathway coordinated regulation, involving various ion channels and receptors, especially those closely related to pain regulation.
L-menthol is a classic agonist of the cold receptor TRPM8, activating TRPM8 channels to produce a cooling sensation and regulate pain signaling. In addition, L-menthol can regulate the TRPV1 and TRPA1 channels, both of which are involved in the regulation of pain and inflammatory responses. By negatively regulating TRPV1, L-menthol can alleviate heat pain hypersensitivity; Regulation of TRPA1 helps relieve inflammatory pain.
L-menthol has a regulatory effect on opioid receptors (OPRM1, OPRD1, OPRK1) and participates in central and peripheral analgesia mechanisms. By enhancing opioid receptor-mediated signaling, L-menthol can exert a synergistic analgesic effect, reducing pain perception.
CNR1 receptors play an important role in pain regulation in the nervous system. L-menthol enhances analgesic effects by modulating CNR1 activity, participating in the regulation of neuroinflammation and pain signals.
L-menthol inhibits cyclooxygenases 1 and 2 (COX-1 and COX-2), reduces prostaglandin synthesis, and thus exerts anti-inflammatory and analgesic effects. This mechanism is similar to that of nonsteroidal anti-inflammatory drugs (NSAIDs), providing a molecular basis for their anti-inflammatory and analgesic properties.
L-menthol also affects the serotonin transporter (SLC6A4) and dopamine D2 receptor (DRD2), regulates neurotransmitter balance in the central nervous system, participates in the regulation of emotions and pain, and may have adjunctive therapeutic effects on chronic pain and related mood disorders.
In summary, L-menthol forms a complex analgesic and antispasmodic network through multi-target coordinated regulation, providing a molecular basis for its multiple pharmacological effects.
The druggability parameters of L-menthol indicate that it has promising potential for drug development. Moderate molecular weight (156.2690) and LogP (3.2688) met the Lipinski rule, indicating good oral bioavailability. A lower TPSA (20.23 Ų) and high blood-brain barrier permeability support its ability to act on the central nervous system.
In terms of safety, the hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test is non-mutagenic, further ensuring its safety. Although water solubility is relatively low, its bioavailability can be improved through formulation process optimization.
Pharmacokinetic studies show that L-menthol is rapidly absorbed orally and widely distributed in the body, especially highly accumulated in the central nervous system. Metabolism mainly occurs through the liver enzyme system, producing various metabolic products that are ultimately excreted by the kidneys. Its half-life is moderate, making it suitable for multiple doses to maintain efficacy.
However, the low water solubility and rapid metabolism of L-menthol may limit its oral efficacy, requiring novel delivery systems such as nanoformulations and liposome encapsulation to enhance its stability and bioavailability.
With its multi-target and multi-mechanism pharmacological properties, L-menthol shows broad prospects in clinical applications. Currently, L-menthol is widely used in topical analgesic plasters, oral cooling agents, anti-itch creams, and other formulations, with good safety and high patient tolerance.
In the future, based on its analgesic and neuromodulatory effects, L-menthol is expected to be developed as an adjunctive drug for treating chronic pain, neuropathic pain, and related psychiatric disorders. Combining modern drug delivery technologies, such as transdermal drug delivery systems and nanocarriers, can further enhance treatment outcomes and patient compliance.
Moreover, L-menthol's applications in antispasmodic and anti-itch areas are worth further exploration, especially regarding its potential therapeutic effects in gastrointestinal dysfunction and skin lesions. By combining precise regulation of molecular targets, personalized treatment is expected in the future.
It should be noted that although L-menthol is relatively safe, its toxicological characteristics at high doses or during long-term use still require systematic evaluation. Preclinical and clinical studies should further clarify their pharmacokinetics, pharmacodynamics, and safety to provide scientific basis for new drug development.
As a classic natural monoterpene alcohol, L-menthol has become a hot topic in natural product pharmacology research due to its unique chemical structure and diverse pharmacological activities. By modulating multiple targets such as TRP channels, opioid receptors, cannabinoid receptors, and cyclooxygenase, it exerts multiple physiological effects including analgesia, antispasmodic, and anti-itch effects, demonstrating significant clinical application value.
Druggability evaluations indicate that L-menthol has good drug development potential, high safety, and can effectively cross the blood-brain barrier, supporting its application in central nervous system diseases. In the future, by combining modern drug delivery technology with precision medicine concepts, L-menthol is expected to play a greater role in pain management and the treatment of related diseases.
Overall, as a safe and effective natural product, L-menthol still needs systematic basic and clinical research to further reveal its mechanism of action, optimize formulation technology, expand its clinical application fields, and promote its transformation into novel natural medicines.
Shenshuai
Wenjing
Hedandan
