Cargando…
Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo
Phytolacca acinosa Roxb (PAR), a traditional Chinese medicine, has been widely used as a diuretic drug for a long period of time for the treatment edema, swelling, and sores. However, it has been reported that PAR might induce hepatotoxicity, while the mechanisms of its toxic effect are still unclea...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645354/ https://www.ncbi.nlm.nih.gov/pubmed/34876912 http://dx.doi.org/10.1155/2021/3303014 |
_version_ | 1784610286382088192 |
---|---|
author | Cao, Dan Zhao, Chongjun Li, Zhiqi Fan, Qiqi Chen, Meilin Jiang, Yangyu Wang, Haiyan Ning, Hanjun Lin, Ruichao Li, Jian |
author_facet | Cao, Dan Zhao, Chongjun Li, Zhiqi Fan, Qiqi Chen, Meilin Jiang, Yangyu Wang, Haiyan Ning, Hanjun Lin, Ruichao Li, Jian |
author_sort | Cao, Dan |
collection | PubMed |
description | Phytolacca acinosa Roxb (PAR), a traditional Chinese medicine, has been widely used as a diuretic drug for a long period of time for the treatment edema, swelling, and sores. However, it has been reported that PAR might induce hepatotoxicity, while the mechanisms of its toxic effect are still unclear. In this study, network toxicology and metabolomic technique were applied to explore PAR-induced hepatotoxicity on zebrafish larvae. We evaluated the effect of PAR on the ultrastructure and the function of the liver, predictive targets, and pathways in network toxicology, apoptosis of liver cells by PCR and western blot, and metabolic profile by GC-MS. PAR causes liver injury, abnormal liver function, and apoptosis in zebrafish. The level of arachidonic acid in endogenous metabolites treated with PAR was significantly increased, leading to oxidative stress in vivo. Excessive ROS further activated the p53 signal pathway and caspase family, which were obtained from KEGG enrichment analysis of network toxicology. The gene levels of caspase-3, caspase-8, and caspase-9 were significantly increased by RT-PCR, and the level of Caps3 protein was also significantly up-regulated through western blot. PAR exposure results in the liver function abnormal amino acid metabolism disturbance and motivates hepatocyte apoptosis, furthermore leading to liver injury. |
format | Online Article Text |
id | pubmed-8645354 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-86453542021-12-06 Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo Cao, Dan Zhao, Chongjun Li, Zhiqi Fan, Qiqi Chen, Meilin Jiang, Yangyu Wang, Haiyan Ning, Hanjun Lin, Ruichao Li, Jian Evid Based Complement Alternat Med Research Article Phytolacca acinosa Roxb (PAR), a traditional Chinese medicine, has been widely used as a diuretic drug for a long period of time for the treatment edema, swelling, and sores. However, it has been reported that PAR might induce hepatotoxicity, while the mechanisms of its toxic effect are still unclear. In this study, network toxicology and metabolomic technique were applied to explore PAR-induced hepatotoxicity on zebrafish larvae. We evaluated the effect of PAR on the ultrastructure and the function of the liver, predictive targets, and pathways in network toxicology, apoptosis of liver cells by PCR and western blot, and metabolic profile by GC-MS. PAR causes liver injury, abnormal liver function, and apoptosis in zebrafish. The level of arachidonic acid in endogenous metabolites treated with PAR was significantly increased, leading to oxidative stress in vivo. Excessive ROS further activated the p53 signal pathway and caspase family, which were obtained from KEGG enrichment analysis of network toxicology. The gene levels of caspase-3, caspase-8, and caspase-9 were significantly increased by RT-PCR, and the level of Caps3 protein was also significantly up-regulated through western blot. PAR exposure results in the liver function abnormal amino acid metabolism disturbance and motivates hepatocyte apoptosis, furthermore leading to liver injury. Hindawi 2021-11-28 /pmc/articles/PMC8645354/ /pubmed/34876912 http://dx.doi.org/10.1155/2021/3303014 Text en Copyright © 2021 Dan Cao et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Cao, Dan Zhao, Chongjun Li, Zhiqi Fan, Qiqi Chen, Meilin Jiang, Yangyu Wang, Haiyan Ning, Hanjun Lin, Ruichao Li, Jian Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo |
title | Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo |
title_full | Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo |
title_fullStr | Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo |
title_full_unstemmed | Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo |
title_short | Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo |
title_sort | combined metabolomics and network toxicology to explore the molecular mechanism of phytolacca acinose roxb-induced hepatotoxicity in zebrafish larvae in vivo |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645354/ https://www.ncbi.nlm.nih.gov/pubmed/34876912 http://dx.doi.org/10.1155/2021/3303014 |
work_keys_str_mv | AT caodan combinedmetabolomicsandnetworktoxicologytoexplorethemolecularmechanismofphytolaccaacinoseroxbinducedhepatotoxicityinzebrafishlarvaeinvivo AT zhaochongjun combinedmetabolomicsandnetworktoxicologytoexplorethemolecularmechanismofphytolaccaacinoseroxbinducedhepatotoxicityinzebrafishlarvaeinvivo AT lizhiqi combinedmetabolomicsandnetworktoxicologytoexplorethemolecularmechanismofphytolaccaacinoseroxbinducedhepatotoxicityinzebrafishlarvaeinvivo AT fanqiqi combinedmetabolomicsandnetworktoxicologytoexplorethemolecularmechanismofphytolaccaacinoseroxbinducedhepatotoxicityinzebrafishlarvaeinvivo AT chenmeilin combinedmetabolomicsandnetworktoxicologytoexplorethemolecularmechanismofphytolaccaacinoseroxbinducedhepatotoxicityinzebrafishlarvaeinvivo AT jiangyangyu combinedmetabolomicsandnetworktoxicologytoexplorethemolecularmechanismofphytolaccaacinoseroxbinducedhepatotoxicityinzebrafishlarvaeinvivo AT wanghaiyan combinedmetabolomicsandnetworktoxicologytoexplorethemolecularmechanismofphytolaccaacinoseroxbinducedhepatotoxicityinzebrafishlarvaeinvivo AT ninghanjun combinedmetabolomicsandnetworktoxicologytoexplorethemolecularmechanismofphytolaccaacinoseroxbinducedhepatotoxicityinzebrafishlarvaeinvivo AT linruichao combinedmetabolomicsandnetworktoxicologytoexplorethemolecularmechanismofphytolaccaacinoseroxbinducedhepatotoxicityinzebrafishlarvaeinvivo AT lijian combinedmetabolomicsandnetworktoxicologytoexplorethemolecularmechanismofphytolaccaacinoseroxbinducedhepatotoxicityinzebrafishlarvaeinvivo |