Oshima Naohiro, Yamashita Tadatoshi, Hyuga Sumiko, Hyuga Masashi, Kamakura Hiroyuki, Yoshimura Morio, Maruyama Takuro, Hakamatsuka Takashi, Amakura Yoshiaki, Hanawa Toshihiko, Goda Yukihiro
National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
Department of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1, Kitakanemaru, Ohtawara city, Tochigi, 324-8501, Japan.
J Nat Med. 2016 Jul;70(3):554-62. doi: 10.1007/s11418-016-0977-1. Epub 2016 Mar 14.
Ephedrine alkaloids (EAs) have been considered the main pharmacologically active substances in Ephedra Herb (, Mao; EH) since they were first identified by Prof. N. Nagai, and are known to induce palpitation, hypertension, insomnia, and dysuria as side effects. Therefore, the administration of drugs containing EH to patients with cardiovascular-related diseases is severely contraindicated. While our previous studies suggest that some of the effects of EH may not be due to EAs, considering their side effects would be expedient to develop a new EAs-free EH extract (EFE). Here, we established a preparation method for EFE and revealed its chemical composition, including the content of herbacetin, a flavonoid aglycon present in EH and a potential putative marker for EFE quality control. In addition, we showed the antiproliferative effects of EFE against the H1975 non-small cell lung cancer (NSCLC) cell line. EFE was prepared from EH extract using the ion exchange resin SK-1B. LC/Orbitrap MS analysis revealed the removal of EAs, 6-methoxykynurenic acid, and 6-hydroxykynurenic acid from the original extract. Quantitative analysis of herbacetin using LC/MS in acid-hydrolyzed EFE showed that its content was 0.104 %. Although several alkaloidal constituents were removed from EH extract, the antiproliferative effect of EFE against H1975 cells was comparable to that of EH extract. These results indicate that EFE retained the anticancer effect of EH and demonstrated its potential for future development as a new herbal medicine with reduced side effects.
自麻黄碱生物碱（EAs）首次由永井教授鉴定以来，它们一直被认为是麻黄草（麻黄；EH）中的主要药理活性物质，并且已知会引起心悸、高血压、失眠和排尿困难等副作用。因此，严禁向患有心血管相关疾病的患者施用含EH的药物。虽然我们之前的研究表明，EH的某些作用可能并非由EAs引起，但考虑到它们的副作用，开发一种新的不含EAs的EH提取物（EFE）将是有利的。在此，我们建立了EFE的制备方法，并揭示了其化学成分，包括草本黄素的含量，草本黄素是EH中存在的一种黄酮苷元，也是EFE质量控制的潜在假定标志物。此外，我们展示了EFE对H1975非小细胞肺癌（NSCLC）细胞系的抗增殖作用。EFE是使用离子交换树脂SK-1B从EH提取物中制备的。液相色谱/轨道阱质谱分析显示，原始提取物中的EAs、6-甲氧基犬尿氨酸和6-羟基犬尿氨酸已被去除。在酸水解的EFE中使用液相色谱/质谱对草本黄素进行定量分析，结果表明其含量为0.104%。虽然从EH提取物中去除了几种生物碱成分，但EFE对H1975细胞的抗增殖作用与EH提取物相当。这些结果表明，EFE保留了EH的抗癌作用，并证明了其作为一种副作用较小的新型草药未来开发的潜力。
