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Radix Scrophulariae (Chinese name: Xuanshen), a traditional Chinese herb, is used for the treatment of hyperthyroidism, and in this study, its mechanisms were evaluated by metabonomics and system pharmacology. To study the anti-hyperthyroidism effects of R. Scrophulariae , a male SD rat (180–220 g) model of hyperthyroidism induced by Euthyrox was used. Thirty rats were randomly distributed into three groups: the Model group, the R. Scrophulariae treatment group (RS group) and the healthy Control group. Using the UHPLC/Q-TOF-MS metabolomics approach, 44 metabolites were found to be profoundly altered in the model group, and the levels of these biomarkers were significantly decreased after treatment with R. Scrophulariae. Forty-four metabolites and 13 signaling pathways related to R. Scrophulariae , including the biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis and sphingolipid metabolism, were explored, and linoleic acid metabolism and sphingolipid metabolism were identified as the most relevant metabolic pathways. In addition, the system pharmacology paradigm revealed that R. Scrophulariae contains 83 active ingredients and is related to 795 genes, and 804 disease genes are related to hyperthyroidism. The construction of the R. Scrophulariaceae -chemical composition-target-hyperthyroidism network identified a total of 112 intersection genes. The enriched gene targets were analyzed, and five pathways were found to be enriched. Among them pathways, the HIF signaling pathway had the highest enrichment score, which indicated that this pathway might be the main signaling pathway related to the treatment of hyperthyroidism by R. Scrophulariae.The integrated approach involving metabolomics and network pharmacology revealed that R. Scrophulariae might play a role in the treatment of hyperthyroidism by regulating the "IL6-APOA1-cholesterol" pathway and disturbing the HIF signaling pathway. The results demonstrate that the combination of metabolomics and network pharmacology could be used to reflect the effects of R. Scrophulariae on the biological network and metabolic state of hyperthyroidism and to evaluate the drug efficacy of R. Scrophulariaceae and its related mechanisms. [ABSTRACT FROM AUTHOR]

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]