Zhang Yida, Bian Xiqing, Yang Jing, Wu Haiying, Wu Jian-Lin, Li Na
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macao, China.
Department of Emergency, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Front Pharmacol. 2019 Mar 22;10:275. doi: 10.3389/fphar.2019.00275. eCollection 2019.
The root of (Caowu in Chinese, CW) is not only commonly used as a traditional Chinese medicine (TCM), but also served as a tonic in China. Due to its high toxicity, clinical poisoning cases induced by CW have frequently been reported. However, the mechanism is still unclear. In this study, alkaloids and altered endogenous metabolites in CW poisoning patients were investigated to elucidate the possible intoxication mechanism. Eighteen alkaloids, including 6 toxic diester diterpenoid alkaloids (DDAs), were determined from the sera of patients. At the same time, 5-(diisopropylamino)amylamine (DIAAA) derivatization-ultrahigh performance liquid chromatography- quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS) approach was applied in the metabolomics analysis to find much more carboxyl-containing metabolites (CCMs), which are the essential components for life and critical to elucidate the mechanism of toxicity. As a result, 32 altered metabolites after poisoning were identified. Among them, hydroxyeicosatetraenoic acids (HETEs) and some dicarboxylic acids were first found to be related to alkaloids toxicity. Finally, biological pathway analysis indicated that the significantly changed metabolites were primarily involved in amino acid metabolism, TCA cycle, fatty acid metabolism, pyruvate metabolism, arachidonic acid metabolism, sphingolipid metabolism and so on. These results can not only provide more information on the mechanism of CW intoxication but also help the clinical diagnosis of CW poisoning.
草乌的根在中国不仅常用作中药，还用作滋补品。由于其毒性高，草乌引起的临床中毒病例屡有报道。然而，其机制仍不清楚。本研究通过对草乌中毒患者体内生物碱及内源性代谢物变化进行研究，以阐明可能的中毒机制。从患者血清中测定了18种生物碱，包括6种有毒的二酯二萜生物碱（DDAs）。同时，采用5-（二异丙基氨基）戊胺（DIAAA）衍生化-超高效液相色谱-四极杆-飞行时间质谱（UHPLC-Q-TOF/MS）方法进行代谢组学分析，以发现更多含羧基代谢物（CCMs），这些是生命的重要组成部分，对阐明毒性机制至关重要。结果，鉴定出中毒后32种代谢物发生改变。其中，羟基二十碳四烯酸（HETEs）和一些二羧酸首次被发现与草乌生物碱毒性有关。最后，生物通路分析表明，显著变化的代谢物主要参与氨基酸代谢、三羧酸循环、脂肪酸代谢、丙酮酸代谢、花生四烯酸代谢、鞘脂代谢等。这些结果不仅可以为草乌中毒机制提供更多信息，还有助于草乌中毒的临床诊断。
