Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride

Wang, Xiao Yan; Lin, Jiaqi; Chen, Tianlu; Zhou, Mingmei; Su, Mingming; Wang, Jia

doi:10.1007/s11306-010-0244-5

Cited by 13 publications

(8 citation statements)

References 32 publications

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“…In some cases of severe hepatic toxicity, such as cirrhosis, BCAAs are used in muscle to create alanine, which is then shuttled to the liver for facilitating pyruvate formation. Previously, Ala level was found to be largely decreased in liver tissue of rats with CCl 4 -induced acute hepatic injury [31]. We observed an increase in BCAAs, with no change in Ala level, a decrease in pyruvate level, and elevated ALT activity in FHF mouse serum, which suggests that ALT is involved in affecting the dynamics of BCAA and pyruvate contents in the mouse.…”

Section: Discussionsupporting

confidence: 48%

A Plant Kavalactone Desmethoxyyangonin Prevents Inflammation and Fulminant Hepatitis in Mice

Chou¹,

Feng

Huang

et al. 2013

PLoS ONE

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Alpinia pricei Hayata is a Formosan plant which has been popularly used as nutraceutical or folk medicine for inflammation and various disorders. An active compound of the plant rhizomes, desmethoxyyangonin (DMY), was identified in this study for its novel effect against endotoxin lipopolysaccharide (LPS)-stimulated inflammation in murine macrophages and LPS/D-galactosamine (LPS/D-GalN)-induced fulminant hepatitis in mice. DMY was observed to significantly inhibit proliferation and activation of T cells ex vivo and the activity of several pro-inflammatory mediators in vitro. DMY also protected LPS/D-GalN−induced acute hepatic damages in mice through inhibiting aminotransferases activities and infiltrations of inflammatory macrophages, neutrophils and pathogenic T cells into the liver tissues. In addition, pretreatment with DMY significantly improved the survival rate of LPS/D-GalN−treated mice to 90% (9/10), compared to LPS/D-GalN−treated group (40%, 4/10). UPLC/MS platform-based comparative metabolomics approach was used to explore the serum metabolic profile in fulminant hepatic failure (FHF) mice with or without the DMY pretreatment. The results showed that LPS/D-GalN−induced hepatic damage is likely through perturbing amino acid metabolism, which leads to decreased pyruvate formation via catalysis of aminotransferases, and DMY treatment can prevent to a certain degree of these alterations in metabolic network in mouse caused by LPS/D-GalN. Mechanistic investigation demonstrated that DMY protects LPS or LPS/D-GalN−induced damages in cell or liver tissues mainly through de-regulating IKK/NFκB and Jak2/STAT3 signaling pathways. This report provides evidence-based knowledge to support the rationale for the use of A. pricei root extract in anti-inflammation and also its new function as hepatoprotetive agent against fulminant hepatitis.

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Section: Discussionsupporting

confidence: 48%

A Plant Kavalactone Desmethoxyyangonin Prevents Inflammation and Fulminant Hepatitis in Mice

Chou¹,

Feng

Huang

et al. 2013

PLoS ONE

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“…The ROC curve for a two-metabolite set (glycine and PAG) outperformed single markers (glycine, PAG, or adenine), highlighting that this set is a promising biomarker that possesses the greatest discriminatory power to predict individual responses to KBR consumption in sedentary overweight/obese adults. Several other studies have supported an association between urinary glycine or PAG levels and status of oxidative stress [47,48,49,50,51,52] or inflammatory stress [52]. Finally, the predictive accuracy of this two-metabolite set was further validated with the LOOCV procedure, because the ROC curve may lead to an overestimation of the AUC if it is constructed using all samples [53].…”

Section: Discussionmentioning

confidence: 99%

Integration of Traditional and Metabolomics Biomarkers Identifies Prognostic Metabolites for Predicting Responsiveness to Nutritional Intervention against Oxidative Stress and Inflammation

et al. 2017

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Various statistical approaches can be applied to integrate traditional and omics biomarkers, allowing the discovery of prognostic markers to classify subjects into poor and good prognosis groups in terms of responses to nutritional interventions. Here, we performed a prototype study to identify metabolites that predict responses to an intervention against oxidative stress and inflammation, using a data set from a randomized controlled trial evaluating Korean black raspberry (KBR) in sedentary overweight/obese subjects. First, a linear mixed-effects model analysis with multiple testing correction showed that four-week consumption of KBR significantly changed oxidized glutathione (GSSG, q = 0.027) level, the ratio of reduced glutathione (GSH) to GSSG (q = 0.039) in erythrocytes, malondialdehyde (MDA, q = 0.006) and interleukin-6 (q = 0.006) levels in plasma, and seventeen NMR metabolites in urine compared with those in the placebo group. A subsequent generalized linear mixed model analysis showed linear correlations between baseline urinary glycine and N-phenylacetylglycine (PAG) and changes in the GSH:GSSG ratio (p = 0.008 and 0.004) as well as between baseline urinary adenine and changes in MDA (p = 0.018). Then, receiver operating characteristic analysis revealed that a two-metabolite set (glycine and PAG) had the strongest prognostic relevance for future interventions against oxidative stress (the area under the curve (AUC) = 0.778). Leave-one-out cross-validation confirmed the accuracy of prediction (AUC = 0.683). The current findings suggest that a higher level of this two-metabolite set at baseline is useful for predicting responders to dietary interventions in subjects with oxidative stress and inflammation, contributing to the emergence of personalized nutrition.

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“…Through the analysis of one or several kinds of biofluids including serum, urine, saliva, and tissue samples, the global and dynamic alterations in metabolism can be deciphered [4]. Therefore, metabolomics has been increasingly used in many applications such as identifying metabolite markers for clinical diagnosis and prognosis [5], monitoring the chemical-induced toxicity [6], exploring the potential mechanism of diverse diseases [7], and assessing therapeutic effects of treatment modalities [8, 9]. Univariate and/or multivariate statistical methods are routinely used in metabolomics studies, aiming at successful classification of samples with metabolic phenotypic variations and identification of potential biomarkers while minimizing the technical variations.…”

Section: Introductionmentioning

confidence: 99%

Random Forest in Clinical Metabolomics for Phenotypic Discrimination and Biomarker Selection

Chen

Cao

Zhang

et al. 2013

Evidence-Based Complementary and Alternative Medicine

Self Cite

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Metabolomic data analysis becomes increasingly challenging when dealing with clinical samples with diverse demographic and genetic backgrounds and various pathological conditions or treatments. Although many classification tools, such as projection to latent structures (PLS), support vector machine (SVM), linear discriminant analysis (LDA), and random forest (RF), have been successfully used in metabolomics, their performance including strengths and limitations in clinical data analysis has not been clear to researchers due to the lack of systematic evaluation of these tools. In this paper we comparatively evaluated the four classifiers, PLS, SVM, LDA, and RF, in the analysis of clinical metabolomic data derived from gas chromatography mass spectrometry platform of healthy subjects and patients diagnosed with colorectal cancer, where cross-validation, R 2/Q 2 plot, receiver operating characteristic curve, variable reduction, and Pearson correlation were performed. RF outperforms the other three classifiers in the given clinical data sets, highlighting its comparative advantages as a suitable classification and biomarker selection tool for clinical metabolomic data analysis.

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Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride

Cited by 13 publications

References 32 publications

A Plant Kavalactone Desmethoxyyangonin Prevents Inflammation and Fulminant Hepatitis in Mice

A Plant Kavalactone Desmethoxyyangonin Prevents Inflammation and Fulminant Hepatitis in Mice

Integration of Traditional and Metabolomics Biomarkers Identifies Prognostic Metabolites for Predicting Responsiveness to Nutritional Intervention against Oxidative Stress and Inflammation

Random Forest in Clinical Metabolomics for Phenotypic Discrimination and Biomarker Selection

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