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Objective To investigate the effect and possible mechanism of extracts of Xuanshen (Scrophularia Root, Radix Scrophulariae) on liver metabolome in rat model of hyperthyroidism. Methods The rat liver metabolites spectrums effected by Euthyrox and Xuanshen extracts were analyzed by using ultra high performance liquid chromatography-time off light-mass spectrometry (UPLCTOFMS). The difference in metabolites spectrums was studied between blank group and model group by using orthogonal partial least squares-discriminant analysis (OPLS DA). The potential biomarkers were found in liver through variable importance projection (VIP). The interventional effects of Xuanshen extracts were discussed through comparing the difference in content of potential biomarkers. Results There were 21 potential biomarkers found in rat liver in model group, and among them 14 metabolites were significantly called back by Xuanshen extracts. The biosynthesis of glycosylphosphatidylinositol (GPI)-anchor, and metabolisms of arachidonic acid, purine, α-linolenic acid, linoleic acid, glutathione and glycerophospholipid were significantly improved by Xuanshen extracts in Euthyrox induced hyperthyroidism rat model. Conclusion Xuanshen extracts can play a role of treating hyperthyroidism through improving relevant liver potential biomarkers and metabolism pathways in hyperthyroidism rat model. [ABSTRACT FROM AUTHOR]