Xiang Yalan, Wang Chao, Wen Jing, Zhang Min, Duan Xiaoyu, Wang Lu, Yan Miao, Li Huande, Fang Pingfei
Department of Pharmacy, The Second Xiangya Hospital, Central South University Changsha 410011 China
Institute of Clinical Pharmacy, Central South University Changsha 410011 China.
RSC Adv. 2020 Dec 16;10(72):44398-44407. doi: 10.1039/d0ra08568e. eCollection 2020 Dec 9.
, a traditional Chinese medicine (TCM), has been widely used to treat paraplegia, facial nerve palsy and myasthenia gravis. However, its clinical application is greatly limited due to its fatal toxicity. To investigate the acute toxicity of and the detoxification effect of , a high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) based urinary metabolomics method was developed in this study. After intraperitoneal injection to rats with extract, the serum biochemical indexes were changed significantly, the liver and kidney showed severe necrosis and edema. Then the poisoned rat model was subsequently used for metabolomics research. Through principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), we finally identified 19 endogenous differential metabolites involved in amino acid metabolism, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, oxidative stress and energy metabolism. In addition, 4 exogenous compounds from (3 prototypes and 1 metabolite) were also identified in the present study. Results showed that the alterations of 23 compounds caused by were significantly reversed after treatment, which indicated that restoring the endogenous metabolic disorder and accelerating the metabolism of the main toxic components might be the possible detoxification mechanisms of . This study may provide an integral understanding for the acute toxicity of and the detoxification effect of , thereby contributing to the clinical use of and .
一种中药，已被广泛用于治疗截瘫、面神经麻痹和重症肌无力。然而，由于其致命毒性，其临床应用受到极大限制。为了研究该中药的急性毒性和该中药的解毒作用，本研究建立了一种基于高效液相色谱串联四极杆飞行时间质谱（HPLC-Q-TOF/MS）的尿液代谢组学方法。给大鼠腹腔注射该中药提取物后，血清生化指标发生显著变化，肝脏和肾脏出现严重坏死和水肿。然后将中毒大鼠模型用于代谢组学研究。通过主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA），我们最终鉴定出19种参与氨基酸代谢、甘油磷脂代谢、三羧酸（TCA）循环、氧化应激和能量代谢的内源性差异代谢物。此外，本研究还鉴定出该中药中的4种外源性化合物（3种原型和1种代谢物）。结果表明，该中药处理后，由其引起的23种化合物的变化得到显著逆转，这表明恢复内源性代谢紊乱和加速主要毒性成分的代谢可能是该中药的可能解毒机制。本研究可能为该中药的急性毒性和解毒作用提供全面的认识，从而有助于该中药及其相关药物的临床应用。
