Identification of Potential Biomarkers from Aconitum carmichaelii, a Traditional Chinese Medicine, Using a Metabolomic Approach
Identification of Potential Biomarkers from Aconitum carmichaelii, a Traditional Chinese Medicine, Using a Metabolomic Approach
复制标题
使用代谢组学方法鉴定中药乌头的潜在生物标志物
DOI：
10.1055/s-0043-121708
复制
发表时间：
2018-04-01
期刊：
影响因子：
2.7
通讯作者：
Kennelly, Edward J.
中科院分区：
文献类型：
--
作者：
Zhao, Dake;Shi, Yana;Kennelly, Edward J.
尽管其毒性众所周知，但乌头属物种是世界各地重要的传统药物。中国人称之为“卡米切利”（carmichaelii）。附子是一种具有镇痛、抗炎作用的传统中药，其主要药理活性成分为乌头碱型二萜生物碱。尽管在传统中药中长期使用卡氏乌头，但尚未开发出用于临床的单一实体乌头生物碱药物。采用UPLC-Q-TOF-MS技术，对云南产的7种紫芝进行了鉴别。非靶向主成分分析得分图发现，所有测试的蜘蛛物种聚类成三个不同的群体，和A.carmichaelii是显着不同的化学比其他7个物种。此外，紫穗槐的主根和侧根也存在显著差异。采用正交偏最小二乘判别分析法，从挥发油中鉴定出8个标记化合物，包括14-乙酰卡拉可林、乌头碱、胭脂碱、呋齐林、次乌头碱、新乌头碱、新乌头碱和塔拉替胺。与阴性和阳性对照相比，这些乌头类生物碱中的四种，呋齐林、次乌头碱、中乌头碱和新乌头碱，以剂量依赖性方式显示出显著的镇痛活性。然而，次乌头碱，新乌头碱，新乌头碱表现出显着的急性毒性活性，而夫齐林在小鼠中显示没有急性毒性，表明这种生物碱的相对安全。这项研究提供了一个很好的例子，说明如何使用代谢组学方法区分真正的药用植物和常见的掺假物，并识别可能开发成新药的化合物。
Despite their well-known toxicity, Aconitum species are important traditional medicines worldwide. Aconitum carmichaelii, 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 A.carmichaelii 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 A.carmichaelii from seven other Aconitum species collected in Yunnan Province. Nontargeted principle component analysis scores plots found that all the tested Aconitum species clustered into three distinct groups, and A.carmichaelii was significantly different chemically than the other seven species. Furthermore, the primary and lateral roots of A.carmichaelii 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.