Mitochondrial toxicity evaluation of traditional Chinese medicine injections with a dual in vitro approach
Graphical Abstract A dual in vitro mitochondrial toxicity assay approach combing the conventional “glucose/galactose” assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells was established in this study. Using this platform, we systematically assessed the mitochon...
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Published in | Frontiers in pharmacology Vol. 13; p. 1039235 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
02.11.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Graphical Abstract
A dual in vitro mitochondrial toxicity assay approach combing the conventional “glucose/galactose” assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells was established in this study. Using this platform, we systematically assessed the mitochondrial toxicity of TCM injections for the first time. Four TCM injections were identified with potential mitochondrial toxicity. Their toxic ingredients were predicted by molecular docking and validated by the dual in vitro approach.
There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate
in vitro
methods. Here, we established a dual
in vitro
mitochondrial toxicity approach combing the conventional “glucose/galactose” assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells. Using this dual
in vitro
approach, for the first time, we systematically assessed the mitochondrial toxicity of TCM injections. Four of the 35 TCM injections, including Xiyanping, Dengzhanhuasu, Shuanghuanglian, and Yinzhihuang, significantly reduced cellular ATP production in galactose medium in the first assay, and presented less cytotoxic in the respiration deficient cells in the second assay, indicating that they have mitochondrial toxicity. Furthermore, we identified scutellarin, rutin, phillyrin, and baicalin could be the potential mitochondrial toxic ingredients in the 4 TCM injections by combining molecular docking analysis with experimental validation. Collectively, the dual
in vitro
approach is worth applying to the safety evaluation of more TCM products, and mitochondrial toxic TCM injections and ingredients found in this study deserve more attention. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was submitted to Predictive Toxicology, a section of the journal Frontiers in Pharmacology Edited by: Albert P. Li, In Vitro ADMET Laboratories, United States Reviewed by: Guoshun Shan, Liaoning University of Traditional Chinese Medicine, China Yongshen Ren, South-Central University for Nationalities, China These authors have contributed equally to this work Min Cao, Shanghai University of Traditional Chinese Medicine, China |
ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2022.1039235 |