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Biomarkers and Mechanism Analysis for Polygoni Multiflori Radix Preparata-Induced Liver Injury by
Liming Wang1, Zhida Wang2, Yanchao Xing1
1State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, China.
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.
Insights
Polygonum Multiflorum Radix Preparata (PMP) extract caused liver injury in rats. Metabolomics identified 16 biomarkers related to bile acid, lipid, and energy metabolism, suggesting cholestasis and lipid dysregulation as key mechanisms.
Area of Science:
- Pharmacology
- Toxicology
- Metabolomics
Background:
- Polygonum Multiflorum Radix Preparata (PMP) is used for liver and kidney health.
- Previous studies indicate PMP can be hepatotoxic, limiting its clinical application.
- The exact toxic compounds and molecular mechanisms of PMP hepatotoxicity remain unclear.
Purpose of the Study:
- To identify potential biomarkers for PMP-induced hepatotoxicity.
- To elucidate the molecular mechanisms underlying PMP's liver toxicity using metabolomics.
Main Methods:
- An untargeted metabolomics approach was employed.
- Plasma samples from rats orally administered PMP extract (PMPE) for 28 days were analyzed.
- Receiver Operating Characteristic (ROC) curve analysis was used to identify specific biomarkers.
Main Results:
- Significant alterations in plasma metabolic profiles were observed in the PMPE-treated group compared to controls.
- Sixteen highly specific biomarkers indicative of liver injury were identified.
- These biomarkers were primarily associated with bile acid, lipid, and energy metabolism, suggesting cholestasis and dysregulated lipid metabolism.
Conclusions:
- This study provides insights into the pathogenesis of PMP-induced liver injury.
- The identified biomarkers may aid in understanding PMP's toxicity.
- Metabonomics offers a valuable approach for the clinical diagnosis of PMP-induced liver injury.
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