Abstract

Previous studies revealed the hepatotoxic effect of aurantio-obtusin on rats. The aim of this study was to identify potential biomarkers of urine caused by aurantio-obtusin. Sprague–Dawley (SD) rats with body weight of 0, 4, 40, and 200 mg/kg were orally given aurantio-obtusin for 28 days, and urine was collected for 24 h after the last administration. The urine metabolites in the aurantio-obtusin group and the control group were analyzed by ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). Twenty-three metabolites were identified as potential biomarkers, and 10 of them were up-regulated, including xanthosine, hippuric acid, 5-L-glutamyl-taurine, etc. The other 13 biomarkers were down-regulated, including thymidine, 3-methyldioxyindole, cholic acid, etc. The significant changes of these biomarkers indicated that purine metabolism, taurine and hypotaurine metabolism, primary bile acid biosynthesis, pyrimidine metabolism, and tryptophan metabolism played an important role in the hepatotoxicity of aurantio-obtusin in rats. In this paper, the safety and potential risk of aurantio-obtusin were studied for the first time by combining the toxicity of aurantio-obtusin with the results of urine metabolomics, which provided information for the mechanism of liver injury induced by aurantio-obtusin.

Highlights

  • Anthraquinone, known as 9,10-anthraquinone, belongs to polycyclic aromatic hydrocarbons

  • The nontargeted metabolomics method was used to study the dynamic changes of urinary metabolite profile and metabolic pathway in the control group and aurantio-obtusin group based on UPLCQTOF/mass spectrometry (MS)

  • A method of urinary metabolomics of aurantioobtusin was established based on the technology of UPLCQTOF/MS

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Summary

Introduction

Anthraquinone, known as 9,10-anthraquinone, belongs to polycyclic aromatic hydrocarbons. Anthraquinone and its derivatives are naturally found in many plants. They are important dietary components of human beings, in peas, cabbage, lettuce, beans, and other vegetables, and the main active components of traditional Chinese medicines (TCMs) such as Polygonum multiflorum Thunb, Rhubarb, Cassiae semen, etc. Anthraquinones have the medicinal value of anti-tumor, anti-bacterial, anti-inflammatory, anti-oxidation, anti-diabetes, and anti-hypertension (Hussain et al, 2015). TCMs containing anthraquinones have been widely used in medicine and functional food. There are increasing reports of adverse reactions caused by taking TCMs containing anthraquinones (Malik and Müller, 2016)

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