Dataset Information

Poria Attenuates Idiosyncratic Liver Injury Induced by Polygoni Multiflori Radix Praeparata.

ABSTRACT: The hepatotoxicity induced by Polygoni Multiflori Radix Praeparata (PM) has aroused great concern throughout the world. Hence, it is worthwhile to perform studies on the detoxification with the combined use of medicinal herbs based on the compatibility theory of traditional Chinese medicine. In this work, the rat model of PM/LPS-induced idiosyncratic liver injury was used. The effects of Poria, Licorice, and Panax notoginseng on rats of PM/LPS-induced liver injury were investigated respectively, hoping to find the most effective herbal medicine to reduce the hepatotoxicity. According to results of biochemical and histological tests, PM could induce the idiosyncratic hepatotoxicity of rats which presented modest inflammation triggered by non-injurious dose of lipopolysaccharide (LPS). We also found that the combined use of Poria and PM in the ratio of 1:2 could significantly ameliorate the PM/LPS-induced liver injury and systemic inflammation. Furthermore, UPLC/QTOF-MS-based metabolomics was performed to identify possible biomarkers and underlying biological pathways. Ten metabolites were expressed differentially among LPS, PM/LPS, and detoxification-treated groups in terms of PCA and OPLS-DA analysis, which could be potential biomarkers. MetaboAnalyst and pathway enrichment analysis revealed that alterations of these metabolites were primarily involved in three pathways: arginine and proline metabolism, primary bile acid biosynthesis and sphingolipid metabolism. This research provides systematic experimental evidences for the hepatoprotective effect of Poria against PM/LPS-induced liver injury for the first time. And these findings may help better understand the underlying mechanisms of pathophysiologic changes in PM/LPS-induced liver injury.

SUBMITTER: Gao D

PROVIDER: S-EPMC5067826 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Poria Attenuates Idiosyncratic Liver Injury Induced by Polygoni Multiflori Radix Praeparata.

Gao Dan D Pang Jing-Yao JY Zhang Cong-En CE Li Chun-Yu CY Tu Can C Zhang Hai-Zhu HZ Niu Ming M Xiong Yin Y Xiao Xiao-He XH Zhao Kui-Jun KJ Gao Wei-Wei WW Wang Jia-Bo JB

Frontiers in pharmacology 20161018

The hepatotoxicity induced by Polygoni Multiflori Radix Praeparata (PM) has aroused great concern throughout the world. Hence, it is worthwhile to perform studies on the detoxification with the combined use of medicinal herbs based on the compatibility theory of traditional Chinese medicine. In this work, the rat model of PM/LPS-induced idiosyncratic liver injury was used. The effects of Poria, Licorice, and Panax notoginseng on rats of PM/LPS-induced liver injury were investigated respectively, ...[more]

PMID: 27803670

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Project description:Polygoni Multiflori Radix (PM) and Rhei radix et rhizoma (rhubarb) contain similar hepatocyte-toxic anthraquinones such as emodin (major free anthraquinone in PM), physcion and their glycosides. In clinical practice, PM hepatotoxicity has been widely reported, although rhubarb is not recognized as hepatotoxic. To clarify the substances basis (key components) of PM hepatotoxicity, based on the characteristic components' similarity within PM, rhubarb and their concocted forms, a comparative sub-acute toxicity study was designed in mice. Nine groups of mice with 28 days of oral administration of these herbal extracts or 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG, major and unique characteristic component in PM)-herb combinations were set as follows: Group-1, control; Group-2, PM ethanol-extract (PME); Group-3, PM praeparata ethanol-extract (PMPE); Group-4, Rhubarb ethanol-extract (RME); Group-5, Steamed rhubarb ethanol-extract (RMPE); Group-6, TSG; Group-7, PMPE-TSG combination; Group-8, RME-TSG combination; Group-9, RMPE-TSG combination. Each experimental group received an equivalent emodin dose of 29 mg/kg except for the TSG group, and an equivalent TSG dose of 1,345 mg/kg except for the PMPE, RME and RMPE groups. The results showed that PME, PMPE-TSG and RME-TSG induced liver lesions and biochemical abnormalities of liver function compared with the control. In contrast, PMPE, RME, RMPE, TSG and RMPE-TSG caused no liver lesions and fewer biochemical abnormalities. Considering the related components, only the co-administration of high doses of TSG and emodin-8-O-β-D-glucoside (EMG, major anthraquinone glycoside in PM) in these groups could cause liver lesions. According to tissue distribution and correlation analysis, EMG dose was positively correlated with the high hepatic emodin and TSG exposure, and the hepatic emodin and TSG exposure were positively correlated with the biochemical abnormalities of liver function. Cell viability test in vitro showed emodin was more hepatotoxic than TSG and EMG, and mainly emodin and TSG of the three had synergistic hepatotoxic effects. Therefore, creatively using rhubarb as a reference, this study revealed that PM hepatotoxicity in mice mainly came from the integrative contribution of TSG, EMG and emodin.

Project description:Polygoni Multiflori Radix (PMR), the dried root of Polygonum Multiflorum Thunb., has been widely used as traditional Chinese medicines in clinical practice for centuries. However, the frequently reported hepatotoxic adverse effects hindered its safe use in clinical practice. This study aims to explore the hepatotoxic effect of PMR extract and the major PMR derived anthraquinones including emodin, chrysophanol, and physcion in mice and the underlying mechanisms based on bile acid homeostasis. After consecutively treating the ICR mice with PMR extract or individual anthraquinones for 14 or 28 days, the liver function was evaluated by measuring serum enzymes levels and liver histological examination. The compositions of bile acids (BAs) in the bile, liver, and plasma were measured by LC-MS/MS, followed by Principal Component Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA). Additionally, gene and protein expressions of BA efflux transporters, bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2), were examined to investigate the underlying mechanisms. After 14-day administration, mild inflammatory cell infiltration in the liver was observed in the physcion- and PMR-treated groups, while it was found in all the treated groups after 28-day treatment. Physcion and PMR extract induced hepatic BA accumulation after 14-day treatment, but such accumulation was attenuated after 28-day treatment. Based on the PLS-DA results, physcion- and PMR-treated groups were partially overlapping and both groups showed a clear separation with the control group in the mouse liver. The expression of Bsep and Mrp2 in the physcion- and PMR-treated mouse liver was decreased after 14-day treatment, while the downregulation was abrogated after 28-day treatment. Our study, for the first time, demonstrated that both PMR extract and tested anthraquinones could alter the disposition of either the total or individual BAs in the mouse bile, liver, and plasma via regulating the BA efflux transporters and induce liver injury, which provide a theoretical basis for the quality control and safe use of PMR in practice.

Dataset Information

Poria Attenuates Idiosyncratic Liver Injury Induced by Polygoni Multiflori Radix Praeparata.

Publications

Poria Attenuates Idiosyncratic Liver Injury Induced by Polygoni Multiflori Radix Praeparata.

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