Von allen Naturstoffen umschmeicheln die Monoterpene unseren Riechsinn in ganz besonderer Weise. Schon beim Aufzählen ihrer Namen riecht es nach Kräutern und Gewürzen, Campher aus Rosmarin und ...Salbei, Thujon aus Wermut, Menthol aus Pfefferminze, Ocimen aus Basilikumöl, Eucalyptol aus Eukalyptus, Carvon aus Kümmel und Pulegon aus Polei‐Minze. Aber nicht immer passt der Duft zum Namen; und das ausgerechnet bei dem am häufigsten vorkommenden Monoterpen, dem Limonen. Riechen wir einmal genauer hin.
Limonen: auf der Suche nach dem verborgenen Duft
Von allen Naturstoffen umschmeicheln die Monoterpene unseren Riechsinn in ganz besonderer Weise. Schon beim Aufzählen ihrer Namen riecht es nach ...Kräutern und Gewürzen, Campher aus Rosmarin und Salbei, Thujon aus Wermut, Menthol aus Pfefferminze, Ocimen aus Basilikumöl, Eucalyptol aus Eukalyptus, Carvon aus Kümmel und Pulegon aus Polei‐Minze. Aber nicht immer passt der Duft zum Namen; und das ausgerechnet bei dem am häufigsten vorkommenden Monoterpen, dem Limonen. Riechen wir einmal genauer hin.
Lukas Hintermann
European journal of organic chemistry,
October 10, 2017, Volume:
2017, Issue:
37
Journal Article
Peer reviewed
“Menthol is one of my favorite chemicals, with its beautiful large crystals, mint odor, and the cooling sensation it causes on skin…” Find out more about this author's research at ...https://doi.org/10.1002/ejoc.201700677.
“Menthol is one of my favorite chemicals, with its beautiful large crystals, mint odor, and the cooling sensation it causes on skin…” Find out more about this author's research at https://doi.org/10.1002/ejoc.201700677.
Menthol ranks with vanilla and citrus as one of the most important flavouring additives. The chemical and biological properties of menthol are reviewed. Display omitted
•Aspects of the chemistry and ...pharmacological properties of menthol are reviewed.•Menthol has found application in diverse fields; pharmaceutical, cosmetic, tobacco, food.•Numerous biological properties have been ascribed to menthol and the mint oils rich in menthol.•The mechanism by which this compound exerts its activity in vitro or in vivo is still poorly understood.
Menthol is a cyclic monoterpene alcohol which possesses well-known cooling characteristics and a residual minty smell of the oil remnants from which it was obtained. Because of these attributes it is one of the most important flavouring additives besides vanilla and citrus. Due to this reason it is used in a variety of consumer products ranging from confections such as chocolate and chewing gum to oral-care products such as toothpaste as well as in over-the-counter medicinal products for its cooling and biological effects. Its cooling effects are not exclusive to medicinal use. Approximately one quarter of the cigarettes on the market contain menthol and small amounts of menthol are even included in non-mentholated cigarettes. Natural menthol is isolated exclusively from Mentha canadensis, but can also be synthesised on industrial scale through various processes. Although menthol exists in eight stereoisomeric forms, (−)-menthol from the natural source and synthesised menthol with the same structure is the most preferred isomer. The demand for menthol is high and it was previously estimated that the worldwide use of menthol was 30–32,000 metric tonnes per annum. Menthol is not a predominant compound of the essential oils as it can only be found as a constituent of a limited number of aromatic plants. These plants are known to exhibit biological activity in vitro and in vivo such as antibacterial, antifungal, antipruritic, anticancer and analgesic effects, and are also an effective fumigant. In addition, menthol is one of the most effective terpenes used to enhance the dermal penetration of pharmaceuticals. This review summarises the chemical and biological properties of menthol and highlights its cooling effects and toxicity.
Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. ...Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat, and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, although other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative that we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol- and WS-12-induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects.
The incorporation of chemo/photothermal/photodynamic therapy in subcellular organelles such as mitochondria has attracted extensive attention recently. Here, we designed mitochondria-targeted hollow ...mesoporous silica nanoparticles (THMSNs) loaded biocompatible phase-change material L-menthol (LM) via a facile method. Meanwhile, antitumor drug doxorubicin (DOX) and near-infrared (NIR) dye indocyanine green (ICG) approved by FDA were simultaneously encapsulated into THMSNs, denoted as THMSNs@LMDI, which showed NIR radiation triggered capacity for cancer treatment. With the mitochondria-targeted ability of triphenylphosphine, the resulting THMSNs@LMDI showed evidently improved cellular internalization and specific accumulation in mitochondria. Under NIR irradiation, the versatile ICG would be bound to simultaneously produce photodynamic and photothermal therapy. Meanwhile, in view of the solid-liquid phase transition feature of gatekeeper LM, THMSNs@LMDI provided a platform for NIR-mediated temperature-responsive DOX release. As a matter of course, these smart subcellular organelle-THMSNs could serve as an effective drug delivery platform for site-specific on-demand chemo/photothermal/photodynamic therapy of cancer.
Transient receptor potential melastatin member 8 (TRPM8) is a calcium ion (Ca
)-permeable cation channel that serves as the primary cold and menthol sensor in humans. Activation of TRPM8 by cooling ...compounds relies on allosteric actions of agonist and membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP
), but lack of structural information has thus far precluded a mechanistic understanding of ligand and lipid sensing by TRPM8. Using cryo-electron microscopy, we determined the structures of TRPM8 in complex with the synthetic cooling compound icilin, PIP
, and Ca
, as well as in complex with the menthol analog WS-12 and PIP
Our structures reveal the binding sites for cooling agonists and PIP
in TRPM8. Notably, PIP
binds to TRPM8 in two different modes, which illustrate the mechanism of allosteric coupling between PIP
and agonists. This study provides a platform for understanding the molecular mechanism of TRPM8 activation by cooling agents.
Deep eutectic solvents have been recently reported as an interesting alternative to improve the therapeutic efficacy of conventional drugs, hence called therapeutic deep eutectic solvents (THEDES). ...The main objective of this work was to evaluate the potential of limonene (LIM) based THEDES as new possible systems for cancer treatment. LIM is known to have antitumor activity, however it is highly toxic and cell viability is often compromised, thus this compound is not selective towards cancer cells. Different THEDES based on LIM were developed to unravel the anticancer potential of such systems. THEDES were prepared by gently mixing saturated fatty acids menthol or ibuprofen (IBU) with LIM. Successful THEDES were obtained for Menthol:LIM (1:1), CA:LIM (1:1), IBU:LIM (1:4) and IBU:LIM(1:8). The results indicate that all the THEDES present antiproliferative properties, but IBU:LIM (1:4) was the only formulation able to inhibit HT29 proliferation without comprising cell viability. Therefore, IBU:LIM (1:4) was the formulation selected for further assessment of anticancer properties. The results suggest that the mechanism of action of LIM:IBU (1:4) is different from isolated IBU and LIM, which suggest the synergetic effect of DES. In this work, we unravel a methodology to tune the selectivity of LIM towards HT29 cell line without compromising cell viability of healthy cells. We demonstrate furthermore that coupling LIM with IBU leads also to an enhancement of the anti-inflammatory activity of IBU, which may be important in anti-cancer therapies.
Menthol, a natural product of the peppermint plant Mentha x piperita (Lamiaceae), is a monoterpene which is widely used as a natural product in cosmetics, a flavoring agent, and as an intermediate in ...the production of other compounds. Various extracts from peppermint contain menthol as a major active constituent and have been used for centuries as traditional medicines for a number of ailments including infections, insomnia, and irritable bowel syndrome as well as an insect repellent. Menthol's characteristic cooling sensation is due, in part, to the activation of sensory neurons generally termed transient receptor potential (TRP) channels, in particular transient receptor potential melastatin family member 8 (TRPM8) and transient receptor potential subfamily A, member 1 (TRPA1). Menthol acts upon TRPM8 receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold response signals at the application site. Aside from its cold-inducing sensation capabilities, menthol exhibits cytotoxic effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA receptors and sodium ion channels resulting in analgesia. Notwithstanding its plethora of benefits, menthol's coldsensitivity response mechanism has been shown to inhibit mucosal recognition of nicotine and cigarette toxins common in mentholated cigarette brands thus potentially leading to toxic effects. Menthol may prove a valuable lead structure for the synthesis of drugs that target multiple receptors involved with a number of pharmacological effects.
The selective conversion of natural or synthetic neral to (1R,6S)-trans-isopiperitenol would enable and expedite sustainable routes to menthol
and cannabinoids
. However, this reaction has been ...considered impossible because its product is more reactive to the required acid catalysts than its starting material, resulting in several side products
. We now show that an unsymmetric, strong and confined chiral acid, a highly fluorinated imino-imidodiphosphate, catalyses this process with excellent efficiency and selectivity. Expanding the method to other α,β-unsaturated aldehydes could enable access to new cannabinoids and menthol derivatives not readily accessible previously. Mechanistic studies suggest that the confined catalyst accomplishes this reaction by binding the product in an unreactive conformation, thereby preventing its decomposition. We also show how (1R,6S)-trans-isopiperitenol can be readily converted to pharmaceutically useful cannabinoids and menthol, each in the shortest and most atom-economic routes so far.
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