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

摘要

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.