A stepwise strategy integrating metabolomics and pseudotargeted spectrum –effect relationship to elucidate the potential hepatotoxic components in Polygonum multiflorum

In this study, we developed a stepwise strategy integrating metabolomics and pseudotargeted spectrum–effect relationship to illuminate the potential hepatotoxic components in PM. First, 112 components were tentatively identified using ultraperformance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS). Second, based on the theory of toxicity attenuation after processing, we combined the UPLC-Q-TOF-MS method and plant metabolomics to screen out the reduced differential components in PM between raw and processed PM. Third, the proposed pseudotargeted MS of 16 differential components was established and applied to 50 batches of PM for quantitative analysis. Fourth, the hepatocytotoxicity of 50 batches of PM was investigated on two hepatocytes, LO2 and HepG2. Last, three mathematical models, gray relational analysis, orthogonal partial least squares analysis, and back propagation artificial neural network, were established to further identify the key variables affecting hepatotoxicity in PM by combining quantitative spectral information with toxicity to hepatocytes of 50 batches of PM. The results suggested that 16 components may have different degrees of hepatotoxicity, which may lead to hepatotoxicity through synergistic effects. Three components (emodin dianthrones, emodin-8-O-β-D-glucopyranoside, PM 14-17) were screened to have significant hepatotoxicity and could be used as toxicity markers in PM as well as for further studies on the mechani...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research