Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, 444-8787, Japan.
Mol Pain. 2012 Nov 29;8:86. doi: 10.1186/1744-8069-8-86.
Essential oils are often used in alternative medicine as analgesic and anti-inflammatory remedies. However, the specific compounds that confer the effects of essential oils and the molecular mechanisms are largely unknown. TRPM8 is a thermosensitive receptor that detects cool temperatures and menthol whereas TRPA1 is a sensor of noxious cold. Ideally, an effective analgesic compound would activate TRPM8 and inhibit TRPA1.
We screened essential oils and fragrance chemicals showing a high ratio of human TRPM8-activating ability versus human TRPA1-activating ability using a Ca2+-imaging method, and identified 1,8-cineole in eucalyptus oil as particularly effective. Patch-clamp experiments confirmed that 1,8-cineole evoked inward currents in HEK293T cells expressing human TRPM8, but not human TRPA1. In addition, 1,8-cineole inhibited human TRPA1 currents activated by allyl isothiocyanate, menthol, fulfenamic acid or octanol in a dose-dependent manner. Furthermore, in vivo sensory irritation tests showed that 1,8-cineole conferred an analgesic effect on sensory irritation produced by TRPA1 agonists octanol and menthol. Surprisingly, 1,4-cineole, which is structurally similar and also present in eucalyptus oil, activated both human TRPM8 and human TRPA1.
1,8-cineole is a rare natural antagonist of human TRPA1 that has analgesic and anti-inflammatory effects possibly due to its inhibition of TRPA1.
精油经常被用于替代医学中作为止痛和抗炎的药物。然而，赋予精油作用的特定化合物以及分子机制在很大程度上是未知的。TRPM8 是一种热敏受体，可检测到凉爽的温度和薄荷醇，而 TRPA1 则是一种有害冷感的传感器。理想情况下，有效的止痛化合物应该激活 TRPM8 并抑制 TRPA1。
我们使用 Ca2+成像方法筛选了精油和香料化学物质，这些物质对人源 TRPM8 的激活能力与人源 TRPA1 的激活能力具有高比例，发现桉叶油中的 1,8-桉叶油醇特别有效。膜片钳实验证实 1,8-桉叶油醇可诱发表达人源 TRPM8 的 HEK293T 细胞中的内向电流，但不会诱发人源 TRPA1。此外，1,8-桉叶油醇以剂量依赖性方式抑制由丙烯基异硫氰酸酯、薄荷醇、全氟辛酸或辛醇激活的人源 TRPA1 电流。此外，体内感觉刺激测试表明 1,8-桉叶油醇对 TRPA1 激动剂辛醇和薄荷醇产生的感觉刺激具有止痛作用。令人惊讶的是，1,4-桉叶油醇，其结构与桉叶油中的 1,8-桉叶油醇相似，也激活了人源 TRPM8 和人源 TRPA1。
1,8-桉叶油醇是一种罕见的天然人源 TRPA1 拮抗剂，具有止痛和抗炎作用，可能是由于其对 TRPA1 的抑制作用。
