title: Toxic Markers of Matrine Determined Using (1) H-NMR-Based Metabolomics in Cultured Cells In Vitro and Rats In Vivo.
abstract: Matrine is one of the main bioactive alkaloids of Sophora flavescens Aiton, which has been widely used to treat various diseases in China. These diseases include viral hepatitis, liver fibrosis, cardiac arrhythmia, skin diseases, and tumors. However, matrine is also the main toxic compound of this herb, and the available biomarkers are not reliable in detecting or quantifying matrine risk. Metabolomics is a powerful tool used to identify early toxicity biomarkers that are specific indicators of damage to biosystems. This study aimed to find the potential biomarkers of the matrine-induced toxic effects in rats and HepG2 cells. The toxicological effects of rats induced by matrine could be derived from the elevated taurine and trimethylamine N-oxide levels and the depletion in hippurate and tricarboxylic acid cycle intermediates, such as 2-oxoglutarate, citrate, and succinate in the urine. Cell metabolomics revealed that the levels of alanine, choline, glutathione, lactate, phosphocholine, and cholesterol showed dose-dependent decreases, whereas the levels of taurine, fatty acid, and unsaturated fatty acid showed dose-dependent increases. Overall, a significant perturbation of metabolites in response to high dose of matrine was observed both in vivo and in vitro, and the selected metabolites particularly represent an attractive marker for matrine-induced toxicity.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China ; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
authors.forename: Zhonghuang
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China ; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China ; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China ; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
authors.forename: Guiyu
authors.initials: G
authors.lastname: Zhang
authors.affiliation: International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Lu
authors.affiliation: International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Jiajie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China ; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Liu