Zhao Dake, Shi Yana, Zhu Xinyan, Liu Li, Ji Pengzhang, Long Chunlin, Shen Yong, Kennelly Edward J
Laboratory of Ecology and Evolutionary Biology, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan University, Kunming, People's Republic of China.
Yunan Institue of Materia Medica, Yunnan Baiyao Group Company Limited, Kunming, People's Republic of China.
Planta Med. 2018 Apr;84(6-07):434-441. doi: 10.1055/s-0043-121708. Epub 2017 Oct 26.
Despite their well-known toxicity, species are important traditional medicines worldwide. , known in Chinese as (fuzi), is an officially recognized traditional Chinese medicine with characteristic analgesic and anti-inflammatory activities, whose principal pharmacological ingredients are considered as aconitine-type diterpene alkaloids. Notwithstanding the long-recorded use of in traditional Chinese medicine, no single-entity aconitum alkaloid drug has been developed for clinical use. UPLC-Q-TOF-MS was used to investigate the marker compounds that can be used to differentiate from seven other species collected in Yunnan Province. Nontargeted principle component analysis scores plots found that all the tested species clustered into three distinct groups, and was significantly different chemically than the other seven species. Furthermore, the primary and lateral roots of also showed significant differences. Using orthogonal partial least squares discriminate analysis analysis, eight marker compounds were identified, including 14-acetylkarakoline, aconitine, carmichaeline, fuziline, hypaconitine, mesaconitine, neoline, and talatisamine. Four of these aconitum alkaloids, fuziline, hypaconitine, mesaconitine, and neoline, showed significant analgesic activity in a dose-dependent manner compared to the negative and positive controls. However, hypaconitine, mesaconitine, and neoline exhibited significant acute toxicity activity, while fuziline showed no acute toxicity in mice, suggesting the relative safety of this alkaloid. This study provides a good example of how to differentiate an authentic medicinal plant from common adulterants using a metabolomics approach, and to identify compounds that may be developed into new drugs.
尽管它们具有众所周知的毒性，但这些物种在全球都是重要的传统药物。附子，在中文中称为（fuzi），是一种官方认可的具有独特镇痛和抗炎活性的传统中药，其主要药理成分被认为是乌头碱型二萜生物碱。尽管附子在传统中药中的使用历史悠久，但尚未开发出单一实体的乌头生物碱药物用于临床。采用超高效液相色谱-四极杆飞行时间质谱联用技术（UPLC-Q-TOF-MS）研究可用于区分附子与云南省采集的其他七种乌头属物种的标记化合物。非靶向主成分分析得分图发现，所有测试的乌头属物种聚为三个不同的组，附子在化学组成上与其他七个物种有显著差异。此外，附子的主根和侧根也表现出显著差异。通过正交偏最小二乘法判别分析，鉴定出8种标记化合物，包括14-乙酰卡拉可林、乌头碱、卡米查林、伏毛铁棒锤碱、次乌头碱、新乌头碱、尼奥灵和塔拉胺。与阴性和阳性对照相比，这四种乌头生物碱（伏毛铁棒锤碱、次乌头碱、新乌头碱和尼奥灵）表现出剂量依赖性的显著镇痛活性。然而，次乌头碱、新乌头碱和尼奥灵表现出显著的急性毒性活性，而伏毛铁棒锤碱在小鼠中未表现出急性毒性，表明该生物碱相对安全。本研究为如何使用代谢组学方法区分正宗药用植物与常见掺假品以及鉴定可能开发成新药的化合物提供了一个很好的例子。
