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. 2021 Nov 23:2021:7677392.
doi: 10.1155/2021/7677392. eCollection 2021.

Biomarkers and Mechanism Analysis for Polygoni Multiflori Radix Preparata-Induced Liver Injury by UHPLC-Q-TOF-MS-Based Metabolomics

Liming Wang  1 , Zhida Wang  2 , Yanchao Xing  1 , Erwei Liu  1 , Xiumei Gao  1 , Linlin Wang  3 , Zhifei Fu  1
Affiliations

Biomarkers and Mechanism Analysis for Polygoni Multiflori Radix Preparata-Induced Liver Injury by UHPLC-Q-TOF-MS-Based Metabolomics

Liming Wang et al. Evid Based Complement Alternat Med. .

Abstract

Background: Polygonum Multiflorum Radix Preparata (PMP), prepared from Polygonum multiflorum Thunb. (PM), is traditionally valued for its liver and kidney-tonifying effects. However, the previous studies showed that PMP was hepatotoxic, which limited its clinical use. Unfortunately, the potential hepatotoxic ingredients and the molecular mechanism are still uncertain.

Objective: The aim of this study was to find out potential biomarkers of hepatotoxicity using metabolomics profile.

Materials and methods: 60% ethanol extract of PMP (PMPE) was prepared. Subsequently, an untargeted metabolomics technology in combination with ROC curve analysis method was applied to investigate the alteration of plasma metabolites in rats after oral administration of PMPE (40 g/kg/d) for 28 days.

Results: Compared to the control group, the significant difference in metabolic profiling was observed in the PMPE-induced liver injury group, and sixteen highly specific biomarkers were identified. These metabolites were mainly enriched into bile acids, lipids, and energy metabolisms, indicating that PMPE-induced liver injury could be related to cholestasis and dysregulated lipid metabolism.

Conclusions: This study is contributed to understand the potential pathogenesis of PMP-induced liver injury. The metabonomic method may be a valuable tool for the clinical diagnosis of PMP-induced liver injury.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The weight curve within 28 days of rats (a), liver index (b), and (c) Pathological sections of liver of rats after 28 days of administration of 60% ethanol extract of PMP (400 times under light microscope) in Blank Control (BC) and 60% ethanol extract of PMP (PMPE) groups ∗p < 0.05, compared with the control group, ∗∗p < 0.01, compared with the control group.
Figure 2
Figure 2
Serum relative levels of ALT, AST, ALP, TG, TBA, and TBIL in BC and PMPE groups, ∗p < 0.05, ∗∗∗p < 0.0001 compared with the control group. ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; TG, triglyceride; TBA, total bile acid; TBIL total bilirubin.
Figure 3
Figure 3
PCA score plots of the LC-MS spectra from plasma. Negative (left) and Positive (right).
Figure 4
Figure 4
OPLS-DA analysis (left) and S-Plot (right) of the rat plasma from LC−MS spectra negative mode and positive mode.
Figure 5
Figure 5
Potential biomarker ROC curve analysis. Positive (left) and Negative (right).
Figure 6
Figure 6
The relative level of potential biomarker content.
Figure 7
Figure 7
Differential metabolites pathway enrichment analysis of PMPE-induced liver injured.
Figure 8
Figure 8
Potential metabolic pathway of PME-induced liver injured.
See this image and copyright information in PMC

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