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Integrative Metabolomics and Proteomics Detected Hepatotoxicity in Mice Associated with Alkaloids from Eupatorium fortunei Turcz.

The traditional Chinese herbal medicine Eupatorium fortunei Turcz. (E. fortunei) has been widely adopted to treat nausea, diabetes, siriasis, and poor appetite. However, E. fortunei contains multiple pyrrolizidine alkaloids (PAs). This study aimed to investigate the hepatotoxicity of total alkaloids...

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Autores principales: Zan, Ke, Lei, Wei, Li, Yaolei, Wang, Ying, Liu, Lina, Zuo, Tiantian, Jin, Hongyu, Ma, Shuangcheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698670/
https://www.ncbi.nlm.nih.gov/pubmed/36356015
http://dx.doi.org/10.3390/toxins14110765
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author Zan, Ke
Lei, Wei
Li, Yaolei
Wang, Ying
Liu, Lina
Zuo, Tiantian
Jin, Hongyu
Ma, Shuangcheng
author_facet Zan, Ke
Lei, Wei
Li, Yaolei
Wang, Ying
Liu, Lina
Zuo, Tiantian
Jin, Hongyu
Ma, Shuangcheng
author_sort Zan, Ke
collection PubMed
description The traditional Chinese herbal medicine Eupatorium fortunei Turcz. (E. fortunei) has been widely adopted to treat nausea, diabetes, siriasis, and poor appetite. However, E. fortunei contains multiple pyrrolizidine alkaloids (PAs). This study aimed to investigate the hepatotoxicity of total alkaloids in E. fortunei (EFTAs) and identify the toxic mechanisms of EFTAs on hepatocytes. Liquid chromatography with a tandem mass spectrometry assay with reference standards indicated that EFTAs mainly consisted of eight PAs whose content accounted for 92.38% of EFTAs. EFTAs markedly decreased mouse body and liver weights and increased the contents of AST and ALT. The histopathological assays demonstrated that, after exposition to EFTAs, the structures of hepatocytes were damaged and the fibrosis and apoptosis in hepatocytes were accelerated. Moreover, EFTAs increased the serum level of inflammatory cytokines and aggravated circulating oxidative stress. A combination of hepatic proteomics and metabolomics was used to investigate the toxic mechanisms of EFTAs. The study revealed that EFTAs seriously disrupted glycerophospholipid metabolism by upregulating the contents of lysophosphatidylglycerol acyltransferase 1 and phosphatidylinositol and downregulating the contents of choline/ethanolamine kinase beta, choline-ethanolamine phosphotransferase 1, phospholipase D4, 1-acylglycerophosphocholine, phosphatidylcholine, and dihydroxyacetone phosphate in the liver, resulting in detrimental inflammation, fibrosis, and apoptosis. This study revealed that EFTAs induced severe hepatotoxicity by disrupting glycerophospholipid metabolism.
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spelling pubmed-96986702022-11-26 Integrative Metabolomics and Proteomics Detected Hepatotoxicity in Mice Associated with Alkaloids from Eupatorium fortunei Turcz. Zan, Ke Lei, Wei Li, Yaolei Wang, Ying Liu, Lina Zuo, Tiantian Jin, Hongyu Ma, Shuangcheng Toxins (Basel) Article The traditional Chinese herbal medicine Eupatorium fortunei Turcz. (E. fortunei) has been widely adopted to treat nausea, diabetes, siriasis, and poor appetite. However, E. fortunei contains multiple pyrrolizidine alkaloids (PAs). This study aimed to investigate the hepatotoxicity of total alkaloids in E. fortunei (EFTAs) and identify the toxic mechanisms of EFTAs on hepatocytes. Liquid chromatography with a tandem mass spectrometry assay with reference standards indicated that EFTAs mainly consisted of eight PAs whose content accounted for 92.38% of EFTAs. EFTAs markedly decreased mouse body and liver weights and increased the contents of AST and ALT. The histopathological assays demonstrated that, after exposition to EFTAs, the structures of hepatocytes were damaged and the fibrosis and apoptosis in hepatocytes were accelerated. Moreover, EFTAs increased the serum level of inflammatory cytokines and aggravated circulating oxidative stress. A combination of hepatic proteomics and metabolomics was used to investigate the toxic mechanisms of EFTAs. The study revealed that EFTAs seriously disrupted glycerophospholipid metabolism by upregulating the contents of lysophosphatidylglycerol acyltransferase 1 and phosphatidylinositol and downregulating the contents of choline/ethanolamine kinase beta, choline-ethanolamine phosphotransferase 1, phospholipase D4, 1-acylglycerophosphocholine, phosphatidylcholine, and dihydroxyacetone phosphate in the liver, resulting in detrimental inflammation, fibrosis, and apoptosis. This study revealed that EFTAs induced severe hepatotoxicity by disrupting glycerophospholipid metabolism. MDPI 2022-11-05 /pmc/articles/PMC9698670/ /pubmed/36356015 http://dx.doi.org/10.3390/toxins14110765 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zan, Ke
Lei, Wei
Li, Yaolei
Wang, Ying
Liu, Lina
Zuo, Tiantian
Jin, Hongyu
Ma, Shuangcheng
Integrative Metabolomics and Proteomics Detected Hepatotoxicity in Mice Associated with Alkaloids from Eupatorium fortunei Turcz.
title Integrative Metabolomics and Proteomics Detected Hepatotoxicity in Mice Associated with Alkaloids from Eupatorium fortunei Turcz.
title_full Integrative Metabolomics and Proteomics Detected Hepatotoxicity in Mice Associated with Alkaloids from Eupatorium fortunei Turcz.
title_fullStr Integrative Metabolomics and Proteomics Detected Hepatotoxicity in Mice Associated with Alkaloids from Eupatorium fortunei Turcz.
title_full_unstemmed Integrative Metabolomics and Proteomics Detected Hepatotoxicity in Mice Associated with Alkaloids from Eupatorium fortunei Turcz.
title_short Integrative Metabolomics and Proteomics Detected Hepatotoxicity in Mice Associated with Alkaloids from Eupatorium fortunei Turcz.
title_sort integrative metabolomics and proteomics detected hepatotoxicity in mice associated with alkaloids from eupatorium fortunei turcz.
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698670/
https://www.ncbi.nlm.nih.gov/pubmed/36356015
http://dx.doi.org/10.3390/toxins14110765
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