Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya Street, 117997 Moscow, Russian Federation.
J Biol Chem. 2012 Sep 21;287(39):32993-3000. doi: 10.1074/jbc.M112.366427. Epub 2012 Aug 1.
A novel compound was identified in the acidic extract of Thymus armeniacus collected in the Lake Sevan region of Armenia. This compound, named "sevanol," to our knowledge is the first low molecular weight natural molecule that has a reversible inhibition effect on both the transient and the sustained current of human ASIC3 channels expressed in Xenopus laevis oocytes. Sevanol completely blocked the transient component (IC(50) 353 ± 23 μM) and partially (∼45%) inhibited the amplitude of the sustained component (IC(50) of 234 ± 53 μM). Other types of acid-sensing ion channel (ASIC) channels were intact to sevanol application, except ASIC1a, which showed more than six times less affinity to it as compared with the inhibitory action on the ASIC3 channel. To elucidate the structure of sevanol, the set of NMR spectra in two solvents (d(6)-DMSO and D(2)O) was collected, and the complete chemical structure was confirmed by liquid chromatography-mass spectrometry with electrospray ionization (LC-ESI(+)-MS) fragmentation. This compound is a new lignan built up of epiphyllic acid and two isocitryl esters in positions 9 and 10. In vivo administration of sevanol (1-10 mg/kg) significantly reversed thermal hyperalgesia induced by complete Freund's adjuvant injection and reduced response to acid in a writhing test. Thus, we assume the probable considerable role of sevanol in known analgesic and anti-inflammatory properties of thyme.
在亚美尼亚塞凡湖地区采集的百里香酸性提取物中发现了一种新型化合物。这种名为“塞万醇”的化合物，据我们所知，是第一个对表达在非洲爪蟾卵母细胞中的人类 ASIC3 通道的瞬态和持续电流具有可逆抑制作用的低分子量天然分子。塞万醇完全阻断了瞬态成分（IC50 为 353±23 μM），并部分（约 45%）抑制了持续成分的幅度（IC50 为 234±53 μM）。除了 ASIC1a 之外，其他类型的酸敏离子通道（ASIC）对塞万醇的应用是完整的，与对 ASIC3 通道的抑制作用相比，它对 ASIC1a 的亲和力低了六倍以上。为了阐明塞万醇的结构，在两种溶剂（d6-DMSO 和 D2O）中收集了一组 NMR 谱，并通过带有电喷雾电离（LC-ESI(+)-MS）碎片的液相色谱-质谱法（LC-ESI(+)-MS）确认了其完整的化学结构。这种化合物是一种新的木脂素，由邻苯二甲酸和两个异柠檬酸酯在 9 位和 10 位组成。体内给予塞万醇（1-10 mg/kg）可显著逆转完全弗氏佐剂注射引起的热痛觉过敏，并减少扭体试验中对酸的反应。因此，我们假设塞万醇在百里香已知的镇痛和抗炎特性中可能发挥重要作用。
