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.
Highlights
Polygoni Multiflori (PM, Heshouwu in Chinese), derived from the roots of Polygonum multiflorum unb., is a widely used Chinese medicinal material in clinic
partial least squares discriminant analysis (PLS-DA) and permutation analysis were performed to evaluate the reliability of the model. e model validation of PLS-DA was performed at 200 permutations analysis (Supplementary Figure S1), and the results indicated that the PLS-DA model was credible and had no overfitting
According to the above results, the levels of alkaline phosphatase (ALP), total bile acid (TBA), and TBIL showed significantly increased accompanied by liver cell degeneration, necrosis, and inflammatory cell infiltration, indicating that the PMPEinduced hepatotoxicity may be related to cholestasis
Summary
Polygoni Multiflori (PM, Heshouwu in Chinese), derived from the roots of Polygonum multiflorum unb., is a widely used Chinese medicinal material in clinic. To reduce toxicity and enhance tonic effect, RPM was usually processed by black bean sauce or by nine cycles of steaming and sun drying to obtain the processed PM (PMP) [2]. The National Medical Products Administration in China has warned of the risk of liver injury from the extracts of RPM and PMP [10]. Extensive experiments have been performed in recent years, the Evidence-Based Complementary and Alternative Medicine potential toxic mechanisms that cause liver injury remain unclear. Erefore, it is urgent and important to establish a method for the early warning of liver injury of PMP. E aim of this study was to find out potential biomarkers of hepatotoxicity using metabolomics profile. Is study is contributed to understand the potential pathogenesis of PMP-induced liver injury. Conclusions. is study is contributed to understand the potential pathogenesis of PMP-induced liver injury. e metabonomic method may be a valuable tool for the clinical diagnosis of PMPinduced liver injury
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