Hepatotoxicity and nephrotoxicity assessment on ethanol extract of Fructus Psoraleae in Sprague Dawley rats using a UPLC–Q‐TOF–MS analysis of serum metabolomics

Abstract

Fructus Psoraleae (FP) is commonly used in the treatment of vitiligo, osteoporosis, and other diseases in clinic. As a result, the toxicity caused by FP is frequently encountered in clinical practice; however, the underlying toxicity mechanism remains unclear. The purpose of this study was to investigate the toxic effect of the ethanol extract of FP (EEFP) in rats and to explore the underlying toxic mechanisms using a metabolomics approach. The toxicity was evaluated by hematological indicators, biochemical indicators, and histological changes. In addition, a serum metabolomic method based on ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight MS (UPLC–Q‐TOF–MS) had been established to investigate the hepatorenal toxicity of FP. Multivariate statistical approaches, such as partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis, were built to evaluate the toxic effects of FP and find potential biomarkers and metabolic pathways. Ten endogenous metabolites had been identified and the related metabolic pathways were involved in phospholipid metabolism, amino acid metabolism, purine metabolism, and antioxidant system activities. The results showed that long‐term exposure to high‐dose EEFP may cause hepatorenal toxicity in rats. Therefore, serum metabolomics can improve the diagnostic efficiency of FP toxicity and make it more accurate and comprehensive.

Psoralea corylifolia L.: a comprehensive review of its botany, traditional uses, phytochemistry, pharmacology, toxicology, quality control and pharmacokinetics

“…The nephrotoxicity of 70% ethanol extracts of PCL (0.54, 1.08, and 1.62 g/kg) in rats was examined using UPLC-Q-TOF–MS serum metabolomics. It was discovered that the 70% ethanol extracts of PCL could interfere with phospholipid metabolism, amino acid metabolism, purine metabolism, and antioxidant system activity, leading to nephrotoxicity [ 161 ]. The furanocoumarins of PCL (20, 40 mg/kg) could interfere the metabolism, excretion and bioavailability of endogenous and exogenous compounds to damage kidney functions by affecting renal organic ion transport system [ 162 ].…”

“…Over 163 chemicals have so far been identified from fresh PCL. A number of phytochemical studies have revealed that PCL primarily contains coumarins , flavonoids , monoterpene phenols , benzofurans (140)(141)(142)(143)(144)(145)(146)(147)(148)(149) and other compounds (150)(151)(152)(153)(154)(155)(156)(157)(158)(159)(160)(161)(162)(163). Among them, coumarins, flavonoids and monoterpene phenols are considered to be the PCL's primary bioactive components.…”

Metabolomic Analysis Reveals the Mechanisms of Hepatotoxicity Induced by Aflatoxin M1 and Ochratoxin A

“…In the present study, we applied the mice liver and serum metabolomics in vivo combined with in vitro (HepG2 cells) to explore the underlying mechanisms for the hepatoxicity induced by AFM1 and OTA. The metabolomics of individual liver or serum has been used to characterize toxicological outcomes induced by various hazard factors, such as ethanol and silica nanoparticles [37][38][39]. However, the combined metabolomics of liver and serum is relatively insufficient.…”

UPLC-MS/MS-Based Rat Serum Metabolomics Reveals the Detoxification Mechanism of Psoraleae Fructus during Salt Processing

“…PF is a widely used Chinese medicine, containing bioactive components such as coumarin, benzofuran, flavonoids, and monoterpenes [ 12 ]. Due to clinical application, it has been found that PF has a toxic effect on the liver [ 9 ], and animal studies have shown that PF has hepatotoxicity and nephrotoxicity to normal rats [ 19 , 20 ]. Traditional Chinese medicine processing technology is an effective means to reduce the toxicity of traditional Chinese medicine.…”