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Gaertn<\/jats:italic>., is commonly used to protect against liver disease. We investigated silybin's protective potential in rat liver against emodin\u2010induced liver injury 4 weeks. It was found that aspartate aminotransferase and direct bilirubin serum biomarkers for liver toxicity significantly increased, and liver histopathology revealed cholestasis and necrosis in rats administered emodin alone, whereas aspartate aminotransferase and total bile acid levels in rats administered emodin and silybin simultaneously were changed compared to rats administered emodin alone. Liver mRNA and protein levels of Cyp7a1\u2014which plays roles in cholesterol metabolism and bile acid synthesis\u2014and Abcb11 (Bsep)\u2014which facilitates bile salt secretion in hepatocyte canaliculi\u2014were significantly altered with emodin, whereas cotreatment with silybin attenuated emodin's adverse effect. Metabolomic analysis using ultra\u2010performance liquid chromatography\u2010quadrupole\u2010time\u2010of\u2010flight\u2010mass spectrometry determined eight potential metabolite biomarkers in serum, urine, and liver tissue. Network analysis was conducted to conceptualize the interplay of genes, metabolites, and metabolic pathways for cholesterol metabolism and bile acid synthesis for liver injury. Overall, rats administered only emodin were shown to be a sound model to investigate fat\u2010associated drug\u2010induced hepatoxicity or liver injury and cotreatment of emodin with silybin prevents fatty liver injury. This metabolomic study revealed that emodin\u2010induced fatty liver injury disrupted bile acid synthesis, vitamin B<jats:sub>6<\/jats:sub>, and glycerophospholipid metabolism pathways and that silybin ameliorates liver injury on these compromised pathways.<\/jats:p>","DOI":"10.1002\/bmc.5469","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T09:34:34Z","timestamp":1659087274000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolic profiling of emodin drug\u2010induced liver injury and silybin treatment in rats using ultra\u2010performance liquid chromatography\u2010quadrupole\u2010time\u2010of\u2010flight\u2010mass spectrometry: A metabolomic and mechanistic approach"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1674-973X","authenticated-orcid":false,"given":"Chang","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing P. 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