Zi-jun?Wua,Li-li?Wang?a, b,Xue?Gaoa,Yue?Hai?a,Wen-li?Liua,Le-mei?Dua,Lei?Zhanga,Ai-hong?Yang?a, b,Nan-nan?Huanga.An important mechanism of herb-induced hepatotoxicity: To produce RMs based on active functional groups-containing ingredients from phytomedicine by binding CYP450s[J].Chinese Herbal Medicines (CHM),2019,11(3):
An important mechanism of herb-induced hepatotoxicity: To produce RMs based on active functional groups-containing ingredients from phytomedicine by binding CYP450s
  
DOI:10.1016/j.chmed.2019.07.001
中文关键词:  
英文关键词:active functional groups  herbal medicines  hepatotoxicity  metabolic activation  reactive metabolites
基金项目:
Author NameAffiliation
Zi-jun?Wua aSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China 
Li-li?Wang?a, b aSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China bTianjin State Key Laboratory of Modern Chinese Medicine, Tianjin 300193, China 
Xue?Gaoa aSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China 
Yue?Hai?a aSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China 
Wen-li?Liua aSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China 
Le-mei?Dua aSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China 
Lei?Zhanga aSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China 
Ai-hong?Yang?a, b aSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China bTianjin State Key Laboratory of Modern Chinese Medicine, Tianjin 300193, China 
Nan-nan?Huanga aSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China 
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中文摘要:
      
英文摘要:
      Reactive metabolites (RMs) generated by hepatic metabolism are thought to play an important role in the pathogenesis of drug-induced liver injury (DILI). Like many synthetic drugs undergoing metabolic activation to form RMs which are often associated with drug toxicity, it is recognized that some herbal components may be also converted to toxic, or even mutagenetic and carcinogenic metabolites by cytochrome P450s (CYP450s). This review focuses on the metabolic activation of herbal components and its liver toxicological implications. By summarizing references, we found that hepatotoxic herbal components via producing RMs have some certain structural dependence. There is a correlation between the generation of RMs and the structures, which provides a good chance for the early discovery of toxic ingredients in Traditional Chinese medicines (TCMs): i) A potential hepatotoxic component information database based on active functional groups can be built, which might provide an early information for the basic research of hepatotoxic substances in TCMs; ii) RMs can combine with CYP450s to form a complete antigen, which eventually leads to an antigen-specific immune response. RMs-CYP450 protein complete antigen can be set up, and the potential idiosyncratic liver toxicity might be predicted by testing RMs-CYP450 protein antibody in plasma.
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