Urine and plasma metabolomics study on potential hepatoxic biomarkers identification in rats induced by Gynura segetum

Qiu, Siyan; Zhang, Haixia; Fei, Qianqian; Zhu, Fang; Wang, Jing; Jia, Xiao‐Bin; Chen, Bin

doi:10.1016/j.jep.2018.01.017

Cited by 15 publications

(8 citation statements)

References 33 publications

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“…The mouse model in which a 30 g/kg decoction of G. segetum dried rhizome was administered by gavage in the morning for 30 days showed features of HSOS, including increased weight ratio of the liver and body, serum transaminase, bilirubin, decreased albumin ( Chen et al, 2011 ), bulging abdomen, a large number of clear ascites, floating bowels, jelly omentum in the abdominal cavity, and congested and swollen or contracted and hard liver with a grainy surface and blunt edges ( Zhu et al, 2011 ). The potential markers of hepatotoxicity induced by the decoction of G. segetum dried rhizome are verified in the animal model as differential metabolites of arginine, creatine, valine, glutamine, and citric acid, which are involved in the regulation of multiple metabolic pathways, primarily amino acid metabolism and energy metabolism ( Qiu S. et al, 2018 ). G. segetum dried rhizome also caused liver injury by dysregulating mitochondrial ROS generation through the SIRT3-SOD2 pathway ( Li et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review

et al. 2020

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Background:Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents.Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as “Gynura,” “antioxidant,” “anti-inflammatory,” or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English.Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species.Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.

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Section: Resultsmentioning

confidence: 99%

Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review

et al. 2020

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“…Urine and fecal samples of each rat were collected on days 0, 10, and 21 according to the degree of hepatotoxicity with metabolic cage and stored at −80°C for further analysis in accordance with techniques found in previous studies by Gou et al ( 2017 ) and Qiu et al ( 2018 ). Animals were euthanized at the end of the trial.…”

Section: Methodsmentioning

confidence: 99%

“…Metabolomics, a part of systems biology, is used to clarify the small molecule metabolite profile of organisms and has applications in toxicology, clinical research diagnosis, etc. The effect of GSrE on endogenous metabolites in the body is still unknown and only a few studies reported the effect of GsrE on endogenous metabolites (Qiu et al, 2018 ). Therefore, metabolomic methods can elucidate the changes of metabolites in different tissues of the body exposed to GSrE and help to find differential biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Gynura segetum root extract (GSrE) induced hepatotoxicity based on metabolomic signatures and microbial community profiling in rats

Li²,

Lu³

et al. 2022

Front. Microbiol.

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In recent years, many reports focus on the hepatotoxicity of Gynura segetum root extract (GSrE), but the interaction between GSrE and the gut microbiota is still unclear. This study investigated the mechanism of GSrE-induced hepatotoxicity of different doses and exposure durations by combining metabolomics and gut microbiota analysis. SD rats were divided into 3 groups: blank, low-dose (7.5 g/kg), and high-dose (15 g/kg) groups. Urine and feces samples were collected on day 0, day 10, and day 21. Metabolomics based on gas chromatography-mass spectrometry (GC-MS) was carried out to identify metabolites and metabolic pathways. 16S rDNA gene sequencing was applied to investigate the composition of gut microbiota before and after GSrE-induced hepatotoxicity. Finally, a correlation analysis of metabolites and gut microbiota was performed. Differential metabolites in urine and feces involved amino acids, carbohydrates, lipids, organic acids, and short chain fatty acids. Among them, L-valine, L-proline, DL-arabinose, pentanoic acid, D-allose, and D-glucose in urine and D-lactic acid and glycerol in fecal metabolites depended on the exposure of time and dose. In addition, 16S rDNA sequencing analysis revealed that GSrE-induced hepatotoxicity significantly altered the composition of gut microbiota, namely, f_Muribaculaceae_Unclassified, Lactobacillus, Bacteroides, Lachnospiraceae_NK4A136_group, f_Ruminococcaceae_Unclassified, Prevotellaceae_Ga6A1_group, and Escherichia-Shigella. The correlation analysis between gut microbiota and differential metabolites showed the crosstalk between the gut microbiota and metabolism in host involving energy, lipid, and amino acid metabolisms. In summary, our findings revealed that peripheral metabolism and gut microbiota disorders were time- and dose-related and the correlation between gut microbiota and metabolites in GSrE-induced hepatotoxicity.

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“…Consistently, a recent study reported that PAs, in a structurally-dependent manner, impaired bile acid homeostasis and secretion in HepaRG cells by inhibiting the expression of hepatobiliary transporters, enzymes mediating bile acid synthesis and conjugation, and several transcription regulators (Waizenegger et al 2021). Moreover, a study on urine and serum metabolomic profile in rats treated with PA-containing Gynura segetum proposed that ten metabolites involved in amino acid metabolism, lipids metabolism, and energy metabolism pathways were potential biomarkers of PA-ILI (Qiu et al 2018). However, currently available metabolomic data are derived from a limited number of PAs, and whether these profiles are common in PA intoxication is largely unknown.…”

Section: Omics Studies Of Pa-induced Toxicitymentioning

confidence: 99%

Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids

Zhu

et al. 2021

Arch Toxicol

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Pyrrolizidine alkaloids (PAs) and PA N-oxides are common phytotoxins produced by over 6000 plant species. Humans are frequently exposed to PAs via ingestion of PA-containing herbal products or PA-contaminated foods. PAs require metabolic activation to form pyrrole-protein adducts and pyrrole-DNA adducts which lead to cytotoxicity and genotoxicity. Individual PAs differ in their metabolic activation patterns, which may cause significant difference in toxic potency of different PAs. This review discusses the current knowledge and recent advances of metabolic pathways of different PAs, especially the metabolic activation and metabolism-mediated cytotoxicity and genotoxicity, and the risk evaluation methods of PA exposure. In addition, this review provides perspectives of precision toxicity assessment strategies and biomarker development for the risk control and translational investigations of human intoxication by PAs.

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Urine and plasma metabolomics study on potential hepatoxic biomarkers identification in rats induced by Gynura segetum

Cited by 15 publications

References 33 publications

Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review

Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review

Investigation of Gynura segetum root extract (GSrE) induced hepatotoxicity based on metabolomic signatures and microbial community profiling in rats

Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids

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