Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Mini Rev Med Chem. 2013 Jan;13(1):124-31.
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.
薄荷醇是薄荷植物 Mentha x piperita（唇形科）的天然产物，是一种广泛用作化妆品天然成分、调味剂和其他化合物生产中间体的单萜。薄荷的各种提取物含有薄荷醇作为主要活性成分，并已被几个世纪以来作为传统药物用于治疗多种疾病，包括感染、失眠和肠易激综合征以及驱虫剂。薄荷醇的特征冷却感觉部分归因于感觉神经元的激活，通常称为瞬时受体电位（TRP）通道，特别是瞬时受体电位 melastatin 家族成员 8（TRPM8）和瞬时受体电位亚家族 A，成员 1（TRPA1）。薄荷醇通过快速增加细胞内钙并通过通道动员钙流来作用于 TRPM8 受体，从而在应用部位诱导冷反应信号。除了诱导冷感的能力外，薄荷醇在癌细胞中表现出细胞毒性作用，诱导恶性细胞生长减少，并与 GABA 受体和钠离子通道协同兴奋，从而产生镇痛作用。尽管薄荷醇有许多益处，但它的冷敏反应机制已被证明会抑制粘膜对薄荷醇香烟品牌中常见的尼古丁和香烟毒素的识别，从而可能导致毒性作用。薄荷醇可能成为针对涉及多种药理作用的多个受体的药物合成的有价值的先导结构。
