摘要
Fructus Psoraleae,which is commonly consumed for the treatment of osteoporosis,bone fracture,and leucoderma,induces liver injury.This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae(EEFP)-induced liver injury in rats.EEFP(1.35,1.80,and 2.25 g·kg^–1)was administrated to Sprague Dawley(SD)rats for 30 d.We measured liver chemistries,histopathology,and quantitative isobaric tags for relative and absolute quantitation(iTRAQ)-based protein profiling.EEFP demonstrated parameters suggestive of liver injury with changes in bile secretion,bile flow rate,and liver histopathology.iTRAQ analysis showed that a total of 4042 proteins were expressed in liver tissues of EEFP-treated and untreated rats.Among these proteins,81 were upregulated and 32 were downregulated in the treatment group.KEGG pathway analysis showed that the drug metabolic pathways of cytochrome P450,glutathione metabolism,glycerolipid metabolism,and bile secretion were enriched with differentially expressed proteins.The expression of key proteins related to the farnesoid X receptor(FXR),i.e.,the peroxisome proliferators-activated receptor alpha(PPAR-α),were downregulated,and multidrug resistance-associated protein 3(MRP3)was upregulated in the EEFP-treated rats.Our results provide evidence that EEFP may induce hepatotoxicity through various pathways.Furthermore,our study demonstrates changes in protein regulation using iTRAQ quantitative proteomics analysis.
Fructus Psoraleae, which is commonly consumed for the treatment of osteoporosis, bone fracture, and leucoderma, induces liver injury. This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae(EEFP)-induced liver injury in rats. EEFP(1.35, 1.80, and 2.25 g·kg–1) was administrated to Sprague Dawley(SD) rats for 30 d. We measured liver chemistries, histopathology, and quantitative isobaric tags for relative and absolute quantitation(iTRAQ)-based protein profiling. EEFP demonstrated parameters suggestive of liver injury with changes in bile secretion, bile flow rate, and liver histopathology. iTRAQ analysis showed that a total of 4042 proteins were expressed in liver tissues of EEFP-treated and untreated rats. Among these proteins, 81 were upregulated and 32 were downregulated in the treatment group. KEGG pathway analysis showed that the drug metabolic pathways of cytochrome P450, glutathione metabolism, glycerolipid metabolism, and bile secretion were enriched with differentially expressed proteins. The expression of key proteins related to the farnesoid X receptor(FXR), i.e., the peroxisome proliferators-activated receptor alpha(PPAR-α), were downregulated, and multidrug resistance-associated protein 3(MRP3) was upregulated in the EEFP-treated rats.Our results provide evidence that EEFP may induce hepatotoxicity through various pathways. Furthermore, our study demonstrates changes in protein regulation using iTRAQ quantitative proteomics analysis.
基金
supported by the the National Key Research and Development Program, Specialized Research on Modernization of TCM (Nos. 2018YFC1708006 and 2018YFC1708003)
National Major New Drug Creation Special Project “National Drug New Varieties Research and Development and Its Key Innovative Technology Topics” (No. 2017ZX09301060-005)
the National Natural Science Foundation of China (No. 81320108029)
Tianshan Cedar Plan (No. 2018XS21)
National “Major Scientific and Technological Special Project for Significant New Drugs Creation” Project (No. 2015ZX09501004-002-004)
Specific Fund for Pub-lic Interest Research of Traditional Chinese Medicine, Ministry of Finance of China (No. 201507004-002)。
