Abstract
A novel strategy was developed to identify hepatotoxic compounds in traditional Chinese medicines (TCMs). It is based on the exposure of HL-7702 cells to a TCM extract, followed by the identification and further determination of potential hepatotoxic compounds accumulated in the cells by liquid chromatography–tandem mass spectrometry (LC–MS/MS). As a case study, potential hepatotoxic components in Chelidonium majus L. were screened out. Five alkaloids (sanguinarine, coptisine, chelerythrine, protopine, and chelidonine) were identified by LC–MS/MS within 10 min, and their intracellular concentrations were first simultaneously measured by LC–MS/MS with a run time of 4 min. A cell viability assay was performed to assess the cytotoxicity of each alkaloid. With their higher intracellular concentrations, sanguinarine, coptisine, and chelerythrine were identified as the main hepatotoxic constituents in Ch. majus. The study provides a powerful tool for the fast prediction of cytotoxic components in complex natural mixtures on a high-throughput basis.
Highlights
Traditional Chinese medicines (TCMs) have long played an important role in health care.The therapeutic efficacy of TCMs has been proven by medical practices in China and has been confirmed in many countries worldwide
A novel strategy based on the use of intracellular accumulation as an indicator of cytotoxicity to screen hepatotoxic components in TCMs has been developed
The simultaneous quantification of multiple components of TCMs in cells was achieved for the first time by LC–MS/MS
Summary
Traditional Chinese medicines (TCMs) have long played an important role in health care.The therapeutic efficacy of TCMs has been proven by medical practices in China and has been confirmed in many countries worldwide. The adverse reactions caused by TCMs are mostly transient and reversible with the cessation of treatment, their hepatic adverse effects may be severe and sometimes even permanent [2]. Examples of some known hepatotoxic TCMs are Polygonum multiflorum, Dioscorea bulbifera, Dichroa febrifuga, Mistletoe Viscum, Melia azedarach, Tripterygium wilfordii, Gynura segetum, and Senecio vulgaris. The mechanisms of liver injury induced by TCMs are still not very clear. Some specific phytochemical ingredients that may cause liver injury have been identified, such as diterpenoid-lactones in T. wilfordii and D. bulbifera and pyrrolizidine alkaloids in G. segetum and S. vulgaris [1]. The identification of hepatotoxic components in TCMs would be helpful to elucidate the hepatoxicity basis of TCMs and the mechanisms of TCMs-induced liver injury
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