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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.<\/jats:p>","DOI":"10.1155\/2021\/3303014","type":"journal-article","created":{"date-parts":[[2021,11,28]],"date-time":"2021-11-28T19:50:06Z","timestamp":1638129006000},"page":"1-13","source":"Crossref","is-referenced-by-count":10,"title":["Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-8526","authenticated-orcid":true,"given":"Dan","family":"Cao","sequence":"first","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 102488, China"},{"name":"Beijing Key Lab for Quality Evaluation of Chinese Materia Medica, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongjun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 102488, China"},{"name":"Beijing Key Lab for Quality Evaluation of Chinese Materia Medica, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqi","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 102488, China"},{"name":"Beijing Key Lab for Quality Evaluation of Chinese Materia Medica, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Fan","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 102488, China"},{"name":"Beijing Key Lab for Quality Evaluation of Chinese Materia Medica, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilin","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjun","family":"Ning","sequence":"additional","affiliation":[{"name":"Oncology Surgery Department, She Xian Hosipital, Handan 056400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0670-4298","authenticated-orcid":true,"given":"Ruichao","family":"Lin","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 102488, China"},{"name":"Beijing Key Lab for Quality Evaluation of Chinese Materia Medica, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8864-0621","authenticated-orcid":true,"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"issue":"5","key":"1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1080\/10286020902849266","article-title":"Phytolacacinoside A, a new triterpenoid saponin from Phytolacca acinosa Roxb","volume":"11","author":"H. 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