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      Intracellular Accumulation as an Indicator of Cytotoxicity to Screen Hepatotoxic Components of Chelidonium majus L. by LC–MS/MS

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          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.

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          Pharmacological activities of Chelidonium majus L. (Papaveraceae).

          Chelidonium majus L. (Papaveraceae) has a long history as being useful for the treatment of many diseases in European countries. This plant is of great interest for its use also in Chinese herbal medicine. The plant contains, as major secondary metabolites, isoquinoline alkaloids, such as sanguinarine, chelidonine, chelerythrine, berberine and coptisine. Other compounds structurally unrelated to the alkaloids have been isolated from the aerial parts: several flavonoids and phenolic acids. C. majus extracts and its purified compounds exhibit interesting antiviral, antitumour and antimicrobial properties both in vitro and in vivo.
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            U.S. food and drug administration

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              Traditional Chinese Medicine and Herb-induced Liver Injury: Comparison with Drug-induced Liver Injury

              Abstract Cases of suspected herb-induced liver injury (HILI) caused by herbal Traditional Chinese Medicines (TCMs) and of drug-induced liver injury (DILI) are commonly published in the scientific literature worldwide. As opposed to the multiplicity of botanical chemicals in herbal TCM products, which are often mixtures of several herbs, conventional Western drugs contain only a single synthetic chemical. It is therefore of interest to study how HILI by TCM and DILI compare with each other, and to what extent results from each liver injury type can be transferred to the other. China is among the few countries with a large population using synthetic Western drugs as well as herbal TCM. Therefore, China is well suited to studies of liver injury comparing drugs with TCM herbs. Despite some concordance, recent analyses of liver injury cases with verified causality, using the Roussel Uclaf Causality Assessment Method, revealed major differences in HILI caused by TCMs as compared to DILI with respect to the following features: HILI cases are less frequently observed as compared to DILI, have a smaller proportion of females and less unintentional rechallenge events, and present a higher rate of hepatocellular injury features. Since many results were obtained among Chinese residents who had access to and had used Western drugs and TCM herbs, such ethnic homogeneity supports the contention that the observed differences of HILI and DILI in the assessed population are well founded.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                29 June 2019
                July 2019
                : 24
                : 13
                : 2410
                Affiliations
                [1 ]Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China
                [2 ]Shenyang Analytical Application Center, Shimadzu (China) Co. Ltd., 167 Qingnian Street, Shenyang 110016, China
                Author notes
                [* ]Correspondence: dixin63@ 123456hotmail.com ; Tel.: +86-24-4352-0568
                Article
                molecules-24-02410
                10.3390/molecules24132410
                6651743
                31261913
                71c7389f-c747-4ee0-a382-ba4056ca1a7a
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 May 2019
                : 27 June 2019
                Categories
                Article

                cytotoxicity,intracellular accumulation,lc–ms/ms,alkaloids,hepatotoxicity,chelidonium majus l.

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