Chongjun Zhao1, Zhe Jia1, Erwen Li1, Xia Zhao1, Ting Han1, Jinghuan Tian2, Farong Li3, Dixin Zou4, Ruichao Lin5. 1. Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Higher Education Garden, Liangxiang, Fangshan District, Beijing 102488, PR China. 2. CCRF (Beijing) Incorporated, Shimao International Center Office Building One, Room, 806, Gongti North Road, Chaoyang District, Beijing, PR China. 3. Key Laboratory of Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, Shanxi Normal University, Xi'an, PR China. 4. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China; College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, PR China. Electronic address: zoudixin@163.com. 5. Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Higher Education Garden, Liangxiang, Fangshan District, Beijing 102488, PR China. Electronic address: linrch307@sina.com.
Abstract
BACKGROUND: Euphorbia kansui is effective in treating various diseases, such as ascites and edema, but its liver toxicity is a major obstacle in its wide use in the clinic. However, further investigations have suggested that Euphorbia kansui can cause liver injury. HYPOTHESIS: The study aims to investigate the effect of Euphorbia kansui exposure on zebrafish, and explain the underlying toxicity mechanisms from a comprehensive perspective. STUDY DESIGN: The 4dpf zebrafish larvae were exposed to Euphorbia kansui at a sub-lethal concentration. METHODS: We evaluated the effect of Euphorbia kansui on the ultrastructure and function of the liver, apoptosis of liver cells by PCR and western blot, and metabolic profile by GC-MS based on sub-lethal concentrations. RESULTS: Our results suggested Euphorbia kansui could lead to liver injury and significant alteration of the metabolomics of the zebrafish larvae in sub-lethal concentration conditions. It could also induce alterations in liver microstructure, hepatic function, gene expression and protein associated with the apoptosis process, as well as endogenous metabolism. KEGG pathway analysis identified some biological processes on the basis of different metabolisms and their associated processes especially for amino acid metabolism. CONCLUSION: The results bring us closer to an in-depth understanding of the toxic effects of Euphorbia kansui on zebrafish liver, which will be significantly helpful in effectively guiding safer clinical application of this herb in the clinic. Furthermore, our results also showed the zebrafish model is reliable for evaluation of Euphorbia kansui extract hepatotoxicity and as a methodological reference for the evaluation of Traditional Chinese Medicine with underlying liver toxicity.
BACKGROUND:Euphorbia kansui is effective in treating various diseases, such as ascites and edema, but its liver toxicity is a major obstacle in its wide use in the clinic. However, further investigations have suggested that Euphorbia kansui can cause liver injury. HYPOTHESIS: The study aims to investigate the effect of Euphorbia kansui exposure on zebrafish, and explain the underlying toxicity mechanisms from a comprehensive perspective. STUDY DESIGN: The 4dpf zebrafish larvae were exposed to Euphorbia kansui at a sub-lethal concentration. METHODS: We evaluated the effect of Euphorbia kansui on the ultrastructure and function of the liver, apoptosis of liver cells by PCR and western blot, and metabolic profile by GC-MS based on sub-lethal concentrations. RESULTS: Our results suggested Euphorbia kansui could lead to liver injury and significant alteration of the metabolomics of the zebrafish larvae in sub-lethal concentration conditions. It could also induce alterations in liver microstructure, hepatic function, gene expression and protein associated with the apoptosis process, as well as endogenous metabolism. KEGG pathway analysis identified some biological processes on the basis of different metabolisms and their associated processes especially for amino acid metabolism. CONCLUSION: The results bring us closer to an in-depth understanding of the toxic effects of Euphorbia kansui on zebrafish liver, which will be significantly helpful in effectively guiding safer clinical application of this herb in the clinic. Furthermore, our results also showed the zebrafish model is reliable for evaluation of Euphorbia kansui extract hepatotoxicity and as a methodological reference for the evaluation of Traditional Chinese Medicine with underlying liver toxicity.
Authors: Filipe G Andrade Godoi; Isabel Forner-Piquer; Basilio Randazzo; Hamid R Habibi; Fabiana L Lo Nostro; Renata Guimarães Moreira; Oliana Carnevali Journal: Front Endocrinol (Lausanne) Date: 2021-06-14 Impact factor: 5.555