1. Systematically explore the potential hepatotoxic material basis and molecular mechanism of Radix Aconiti Lateralis based on the concept of toxicological evidence chain (TEC).
- Author
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Zhang K, Liu C, Yang T, Li X, Wei L, Chen D, Zhou J, Yin Y, Yu X, and Li F
- Subjects
- Alkaloids blood, Alkaloids isolation & purification, Animals, Apoptosis drug effects, Chemical and Drug Induced Liver Injury blood, Chemical and Drug Induced Liver Injury metabolism, China, Drugs, Chinese Herbal isolation & purification, Drugs, Chinese Herbal pharmacokinetics, Male, Medicine, Chinese Traditional, Oxidative Stress drug effects, Rats, Rats, Wistar, Aconitum chemistry, Alkaloids toxicity, Chemical and Drug Induced Liver Injury pathology, Drugs, Chinese Herbal toxicity, Models, Biological
- Abstract
Radix aconiti lateralis (Fuzi) is widely used in China as a traditional Chinese medicine for the treatment of asthenia, pain and inflammation. However, its toxic alkaloids often lead to adverse reactions. Currently, most of the toxicity studies on Fuzi are focused on the heart and nervous system, and more comprehensive toxicity studies are needed. In this study, based on the previous reports of Fuzi hepatotoxicity, serum pharmacochemistry and network toxicology were used to screen the potential toxic components of Heishunpian(HSP), a processed product of Fuzi, and to explore the possible mechanism of HSP-induced hepatotoxicity. The results obtained are expressed based on the toxicological evidence chain (TEC). It was found that 22 potential toxic components screened can affect Th17 cell differentiation, Jak-STAT signaling pathway, glutathione metabolism, and other related pathways by regulating AKT1, IL2, F2, GSR, EGFR and other related targets, which induces oxidative stress, metabolic disorders, cell apoptosis, immune response, and excessive release of inflammatory factors, eventually inducing liver damage in rats. This is the first study on HSP-induced hepatotoxicity based on the TEC concept, providing references for further studies on the toxicity mechanism of Fuzi., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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