Screening and verification of linearly dependent biomarkers with acute toxicity induced by Aconiti Radix based on liquid chromatography-mass spectrometry-based metabolite profiling

Abstract

Aconiti Radix, with its unique anti-inflammatory and analgesic effects, is a well-known form of traditional medication; however, improper use of the Aconiti Radix drug often leads to severe acute toxicity. Raw Aconiti Radix ethanol extraction is the most toxic ingredient, followed by raw Aconiti Radix water extraction; processed products have less toxic ingredients. Current clinical examinations primarily use biochemical tests and histopathological examination, but such approaches lack specificity, are time-consuming, and have low sensitivity, which can easily lead to false positive results. Therefore, a fast and accurate way to evaluate acute toxicity is needed. We have established a method that combines metabonomics with trend analysis of a gavage concentration series to find and validate acute toxicity biomarkers of Aconiti Radix. The purpose of this study is to identify Aconiti Radix acute toxicity biomarkers based on UPLC-Q-TOF-MS metabonomics technology. We use relative amounts of biomarkers with dosage and degree of toxicity to determine a dose-dependent trend; these substances may be exclusive Aconiti Radix acute toxicity biomarkers. These exclusive biomarkers were validated both in water extraction of Aconiti Radix and drug incompatibility with Aconiti Radix Cocta–Pinelliae rhizoma couple medicines; ultimately, the acute toxicity biomarkers (shikimic acid, L-acetylcarnitine, LysoPC (22:5), L-valine) were determined. This new method provides a better way to discover and validate specific metabonomics endogenous small molecule compounds.