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Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats.

ABSTRACT: Our previous study showed that kurarinone was the main hepatotoxic ingredient of Sophora flavescens, accumulating in the liver. This study characterized the mechanism of Sophora flavescens extract (ESF) hepatotoxicity and hepatic accumulation of kurarinone. ESF impaired hepatic function and caused fat accumulation in the liver after oral administration (1.25 and 2.5 g/kg for 14 days in rats). Serum metabolomics evaluation based on high-resolution mass spectrometry was conducted and real-time PCR was used to determine the expression levels of CPT-1, CPT-2, PPAR-?, and LCAD genes. Effects of kurarinone on triglyceride levels were evaluated in HL-7702 cells. Tissue distribution of kurarinone and kurarinone glucuronides was analyzed in rats receiving ESF (2.5 g/kg). Active uptake of kurarinone and kurarinone glucuronides was studied in OAT2-, OATP1B1-, OATP2B1-, and OATP1B3-transfected HEK293 cells. Our results revealed that after oral administration of ESF in rats, kurarinone glucuronides were actively transported into hepatocytes by OATP1B3 and hydrolyzed into kurarinone, which inhibited fatty acid ?-oxidation through the reduction of l-carnitine and the inhibition of PPAR-? pathway, ultimately leading to lipid accumulation and liver injury. These findings contribute to understanding hepatotoxicity of kurarinone after oral administration of ESF.

SUBMITTER: Jiang P

PROVIDER: S-EPMC6150336 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats.

Jiang Peng P Zhang Xiuwen X Huang Yutong Y Cheng Nengneng N Ma Yueming Y

Molecules (Basel, Switzerland) 20171025 11

Our previous study showed that kurarinone was the main hepatotoxic ingredient of <i>Sophora flavescens</i>, accumulating in the liver. This study characterized the mechanism of <i>Sophora flavescens</i> extract (ESF) hepatotoxicity and hepatic accumulation of kurarinone. ESF impaired hepatic function and caused fat accumulation in the liver after oral administration (1.25 and 2.5 g/kg for 14 days in rats). Serum metabolomics evaluation based on high-resolution mass spectrometry was conducted and ...[more]

PMID: 29068394

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Project description:Plant secondary metabolites (SMs) play a crucial role in plant defense against pathogens and adaptation to environmental stresses, some of which are produced from medicinal plants and are the material basis of clinical efficacy and vital indicators for quality evaluation of corresponding medicinal materials. The influence of plant microbiota on plant nutrient uptake, production, and stress tolerance has been revealed, but the associations between plant microbiota and the accumulation of SMs in medicinal plants remain largely unknown. Plant SMs can vary among individuals, which could be partly ascribed to the shift in microbial community associated with the plant host. In the present study, we sampled fine roots and rhizosphere soils of Sophora flavescens grown in four well-separated cities/counties in China and determined the taxonomic composition of rhizosphere bacterial communities using Illumina 16S amplicon sequencing. In addition, the association of the rhizosphere bacterial microbiota with the accumulation of alkaloids in the roots of S. flavescens was analyzed. The results showed that S. flavescens hosted distinct bacterial communities in the rhizosphere across geographic locations and plant ages, also indicating that geographic location was a larger source of variation than plant age. Moreover, redundancy analysis revealed that spatial, climatic (mean annual temperature and precipitation), and edaphic factors (pH and available N and P) were the key drivers that shape the rhizosphere bacterial communities. Furthermore, the results of the Mantel test demonstrated that the rhizosphere bacterial microbiota was remarkably correlated with the contents of oxymatrine, sophoridine, and matrine + oxymatrine in roots. Specific taxa belonging to Actinobacteria and Chloroflexi were identified as potential beneficial bacteria associated with the total accumulation of matrine and oxymatrine by a random forest machine learning algorithm. Finally, the structural equation modeling indicated that the Actinobacteria phylum had a direct effect on the total accumulation of matrine and oxymatrine. The present study addresses the association between the rhizosphere bacterial communities and the accumulation of alkaloids in the medicinal plant S. flavescens. Our findings may provide a basis for the quality improvement and sustainable utilization of this medicinal plant thorough rhizosphere microbiota manipulation.

Dataset Information

Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats.

Publications

Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats.

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