Dataset Information

Rapid Discovery of the Potential Toxic Compounds in Polygonum multiflorum by UHPLC/Q-Orbitrap-MS-Based Metabolomics and Correlation Analysis.

ABSTRACT: The dry roots of Polygonum multiflorum (PM), involving both the raw and processed materials, are widely used as the traditional Chinese medicine for treating various diseases in China. Hepatotoxicity has been occasionally reported in patients who consume PM. Unfortunately, no definite criteria are currently available regarding the processing technology of PM for reduction the toxicity. In this work, we aimed to investigate the variations of PM metabolite profiles induced by different processing technologies by UHPLC/Q-Orbitrap-MS and multivariate statistical analysis, and to discover the potential toxic compounds by correlating the cytotoxicity of L02 cell with the contents of metabolites in raw and processed PM samples. We could identify two potential toxic compounds, emodin-8-O-glucoside and torachrysone-O-hexose, which could be selected as the toxic markers to evaluate different processing methods. The results indicated all processed PM samples could decrease the cytotoxicity on L02 cell. The best processing technology for PM process was to steam PM in black soybean decoction (BD-PM) for 24 h.

SUBMITTER: Han L

PROVIDER: S-EPMC6477936 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Rapid Discovery of the Potential Toxic Compounds in <i>Polygonum multiflorum</i> by UHPLC/Q-Orbitrap-MS-Based Metabolomics and Correlation Analysis.

Han Lifeng L Wang Piao P Wang Yulan Y Zhao Qianyu Q Zheng Fang F Dou Zhiying Z Yang Wenzhi W Hu Limin L Liu Caixiang C

Frontiers in pharmacology 20190416

The dry roots of <i>Polygonum multiflorum</i> (PM), involving both the raw and processed materials, are widely used as the traditional Chinese medicine for treating various diseases in China. Hepatotoxicity has been occasionally reported in patients who consume PM. Unfortunately, no definite criteria are currently available regarding the processing technology of PM for reduction the toxicity. In this work, we aimed to investigate the variations of PM metabolite profiles induced by different proc ...[more]

PMID: 31057397

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Project description:BackgroundThe idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury.MethodsSerum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites.ResultsThe results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism.ConclusionsThese findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.

Project description:BackgroundIcaritin (ICT) has been previously demonstrated to display protective effects against cerebral ischemic reperfusion (I/R) by inhibiting oxidative stress, but the mechanism remains unclear. This study aimed to explore the mechanism from the perspective of metabolomics.MethodsA mice cerebral artery occlusion/reperfusion (MCAO/R) model was explored to mimic cerebral ischemic reperfusion and protective effect of ICT was assessed by neurologic deficit scoring, infarct volume and brain water content. Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry (UHPLC-ESI-QE-Orbitrap-MS) based metabolomic was performed to explore potential biomarkers. Brain tissue metabolic profiles were analyzed and metabolic biomarkers were identified through multivariate data analysis. The protein levels of Nrf2, HO-1 and HQO1 were assayed by western blot. The release of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were detected using corresponding assay kits.ResultsThe results showed that after ICT treatment, the neurological deficit, cerebral infarction area, brain edema and the level of MDA in brain tissue of MCAO/R mice were significantly reduced. Meanwhile, ICT enhanced the activity of SOD, CAT and GSH-Px. Western blot results confirmed that ICT up-regulated the protein levels of antioxidant-related protein including Nrf2, HO-1 and NQO1. According to the metabolomic profiling of brain tissues, clear separations were observed among the Sham, Model and ICT groups. A total of 44 biomarkers were identified, and the identified biomarkers were mainly related to linoleic acid metabolism, arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, arginine biosynthesis, arginine and proline metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism and purine metabolism, respectively. At the same time, the inhibitory effect of ICT on arachidonic acid and linoleic acid in brain tissue, as well as the promoting effect on taurine, GABA, NAAG, may be the key factors for the anti-neurooxidative function of mice after MCAO/R injury.ConclusionOur results demonstrate that ICT has benefits for MCAO/R injury, which are partially related to the suppression of oxidative stress via stimulating the Nrf2 signaling and regulating the production of arachidonic acid, linoleic acid, taurine, GABA, NAAG in brain tissue.

Dataset Information

Rapid Discovery of the Potential Toxic Compounds in Polygonum multiflorum by UHPLC/Q-Orbitrap-MS-Based Metabolomics and Correlation Analysis.

Publications

Rapid Discovery of the Potential Toxic Compounds in <i>Polygonum multiflorum</i> by UHPLC/Q-Orbitrap-MS-Based Metabolomics and Correlation Analysis.

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