Investigation of the detoxification effect of licorice on Semen Strychni-induced acute toxicity in rats using a HPLC-Q-TOF/MS-based metabolomics approach.
Investigation of the detoxification effect of licorice on Semen Strychni-induced acute toxicity in rats using a HPLC-Q-TOF/MS-based metabolomics approach.
复制标题
应用HPLC-Q-TOF/MS代谢组学方法研究甘草对马钱子急性毒性的解毒作用。
DOI：
10.1039/d0ra08568e
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发表时间：
2020-12-09
期刊：
影响因子：
3.9
通讯作者：
Fang, Pingfei
中科院分区：
文献类型：
--
作者：
Xiang, Yalan;Wang, Chao;Wen, Jing;Zhang, Min;Duan, Xiaoyu;Wang, Lu;Yan, Miao;Li, Huande;Fang, Pingfei
马钱子是一种传统中药，已被广泛用于治疗截瘫、面神经麻痹和重症肌无力。然而，由于其致命的毒性，其临床应用受到极大的限制。为了研究马钱子的急性毒性和甘草的解毒作用，建立了基于高效液相色谱串联四极杆飞行时间质谱仪的尿液代谢组学方法。马钱子提取液给大鼠腹腔注射后，血清生化指标发生明显变化，肝、肾组织出现严重的坏死和水肿。然后，中毒的大鼠模型随后被用于代谢组学研究。通过主成分分析和正交偏最小二乘判别分析，最终鉴定出19种内源差异代谢物，参与氨基酸代谢、甘油磷脂代谢、三羧酸循环、氧化应激和能量代谢。此外，本研究还从马钱子中鉴定了4个外源化合物(3个原型和1个代谢物)。结果表明，经甘草处理后，马钱子引起的23种化合物的变化明显逆转，提示恢复内源性代谢紊乱，促进主要毒性成分的代谢可能是其解毒机制之一。本研究为了解马钱子的急性毒性和甘草的解毒作用提供了一个完整的认识，从而为马钱子和甘草的临床应用提供参考。生物标志物和代谢途径为了解马钱子的急性毒性和甘草的解毒作用提供了完整的认识。
Semen Strychni, 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 Semen Strychni and the detoxification effect of licorice, 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 Semen Strychni 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 Semen Strychni (3 prototypes and 1 metabolite) were also identified in the present study. Results showed that the alterations of 23 compounds caused by Semen Strychni were significantly reversed after licorice 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 licorice. This study may provide an integral understanding for the acute toxicity of Semen Strychni and the detoxification effect of licorice, thereby contributing to the clinical use of Semen Strychni and licorice. Biomarkers and metabolomic pathway provide an integral understanding for the acute toxicity of Semen Strychni and the detoxification effect of licorice.
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影响因子：
2.5
作者：
Corbin KD;Zeisel SH
通讯作者：
Zeisel SH
影响因子：
3.4
作者：
de Graaf, RA;van Kranenburg, A;Nicolay, K
通讯作者：
Nicolay, K
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
2.4
作者：
Bhati, Rajesh;Singh, Anupama;Bhandari, Anil
通讯作者：
Bhandari, Anil
影响因子：
2.3
作者：
Luginbuhl, Marc;Konig, Stefan;Weinmann, Wolfgang
通讯作者：
Weinmann, Wolfgang