{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:21:24Z","timestamp":1787818884318,"version":"build-2784847793"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Esculentoside A (EsA) is a kind of triterpenoid saponins from the root tuber of <jats:italic>Phytolacca acinosa<\/jats:italic> Roxb. It has extensive medicinal\u00a0activity, such as antibacterial, anti\u2010inflammatory, immune regulation, and cell proliferation inhibition. However, some researches suggested that EsA can cause hepatotoxicity, whose\u00a0mechanism is not precise. To ensure the safety and reliability in the clinical use of <jats:italic>Phytolacca acinosa<\/jats:italic> Roxb., it is necessary to establish a rapid and accurate method to evaluate the toxicity, analyze and verify the toxicity mechanism of EsA. Therefore, this research explored\u00a0the mechanism of hepatotoxicity induced by EsA in rats and analyzed endogenous metabolites' changes in rat plasma by combining network toxicology with non\u2010targeted metabolomics. We obtained 58 critical targets of EsA induced hepatotoxicity in rats based on the strategy of network toxicology, including albumin, mitogen\u2010activated protein kinase 1, Caspase\u20103, etc. Many important pathways were obtained by Kyoto Encyclopedia of Genes and Genomes enrichment analysis, such as HIF\u20101\u00a0signaling pathway, TNF\u00a0signaling pathway, IL\u201017 signaling pathway, and other concerning pathways. Sixteen biomarkers, including 5\u2010hydroxykynurenamine, <jats:italic>N<\/jats:italic>\u2010acetylserotonin,\u00a0palmitic acid, etc., were screened from rat plasma using Ultra\u2010performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC\u2010Q\u2010TOF\/MS), mainly involve Glycerophospholipid metabolism, Tryptophan metabolism, and other metabolic pathways. Further analysis showed that EsA may induce liver injury by activating oxidative stress and energy metabolism disorders, triggering inflammation and apoptosis.<\/jats:p>","DOI":"10.1002\/jbt.22761","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T10:25:47Z","timestamp":1617186347000},"page":"1-15","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Integrating non\u2010targeted metabolomics and toxicology networks to study the mechanism of Esculentoside A\u2010induced hepatotoxicity in rats"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0484-3545","authenticated-orcid":false,"given":"Tao","family":"He","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanxin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingshuang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Han","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxian","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmei","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town Fangshan\u00a0District  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2014.12.025"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-14-343"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.7740\/kjcs.2015.60.3.366"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2012.06.018"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2020.122123"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.10.022"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2012.09.002"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2009.09.022"},{"key":"e_1_2_7_10_1","first-page":"443","volume":"43","author":"Zhang C.","year":"2020","journal-title":"Drug Eval.\u00a0Res."},{"key":"e_1_2_7_11_1","first-page":"4974","volume":"50","author":"Yang X.","year":"2019","journal-title":"Chin. 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