A Study of NMR-Based Hepatic and Serum Metabolomics in a Liver Injury Sprague–Dawley Rat Model Induced by Psoralen

Abstract

Psoralen is the main active component of Psoralea corylifolia and is used as a marker to assess its quality. The effects of psoralen on animals have been well characterized. However, the molecular pathway of its toxicity is not fully understood. In this study, the toxic effects of psoralen administration (60 mg/kg) for 7 days in Sprague-Dawley rats were observed. Serum biochemistry and liver histopathology were further investigated. Proton nuclear magnetic resonance was applied to characterize the metabolic profile of liver toxicity induced by psoralen and to find changed metabolites in rat serum and liver. It was revealed that visceral coefficients and serum biochemistry indexes were significantly changed in rats with psoralen-induced liver injury. Furthermore, the histopathological examination exhibited that the liver might be the target organ for psoralen. Metabolic analysis of both serum and liver samples further proved the liver was the target of toxicity of psoralen. Multivariate analysis identified 7 metabolites in serum samples and 15 in liver samples as potential biomarkers in liver injury induced by psoralen. In addition, our results suggest that psoralen can cause a disturbance in amino acid metabolism, especially valine, leucine, and isoleucine biosynthesis in both serum and liver samples. In conclusion, we combined the results of toxicity and metabolomics induced by psoralen and provide useful information about the safety and potential risks of psoralen and Psoralea corylifolia.

The mechanism of Psoralen and Isopsoralen hepatotoxicity as revealed by hepatic gene expression profiling in SD rats

“…In this study, ALT level was elevated with isopsoralen administration while AST level increased by either psoralen or isopsoralen addition. This is consistent with our previous research that psoralen and isopsoralen exhibit hepatotoxicity as reflected by surged AST and ALT, pathological hepatic change and disturbed the amino acid metabolism …”

“…This is consistent with our previous research that psoralen and isopsoralen exhibit hepatotoxicity as reflected by surged AST and ALT, pathological hepatic change and disturbed the amino acid metabolism. 16,17 However, the underlying mechanism of psoralen-and isopsoralen-induced hepatotoxicity is not known yet. In this study, cDNA chip and bioinformatics analysis tools were F I G U R E 4 Interaction network of intersection genes.…”

Clinicopathological features of Bu Gu Zhi‐induced liver injury, a long‐term follow‐up cohort study

“…However, the duration of hospitalization was significantly longer in the severe group. (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) .343…”

“…19 Several case reports of liver injury induced by BGZ have been reported worldwide, highlighting the potential hepatoxic effects of this herb. 17,[21][22][23][24][25][26][27][28][29] However, the characteristics of BGZ-induced liver injury (BGZILI) including latency, causality, clinical phenotypes, severity and long-term prognosis after dechallenge (ie, stopping of a drug, usually after an adverse event or at the end of planned treatment) are unknown. 22,28,29 We herein describe the clinical and pathological features of BGZILI in 40 patients.…”

Psoralen inhibits malignant proliferation and induces apoptosis through triggering endoplasmic reticulum stress in human SMMC7721 hepatoma cells

“…Additionally, psoralen is the main active component of Psoralea corylifolia (L.) ( Fig. 1a) and is used as marker to assess its quality [16,17], which can inhibit the proliferation of adrenocortical tumors Y1 cells and pituitary tumor AtT20 cells [18]. Psoralen is a kind of furocoumarin, the molecular formula of psoralen is C 11 H 6 O 3 , with molecular weight of 186.1 and dissolved in DMSO.…”