Effects of Bailing capsule on diabetic nephropathy based on UPLC-MS urine metabolomics

Xu, Junnan; Yuan, Qing; Wu, Kang; Li, Xiubin; Zhao, Yuanyu

doi:10.1039/c9ra05046a

Cited by 8 publications

(9 citation statements)

References 35 publications

(39 reference statements)

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“…Finally, we explored the underlying mechanism of Sac/Val ameliorating renal damage from the aspect of plasma metabolomics. Tryptophan metabolism was more active in DKD and En groups, which further validates previous reports (23,49). Disturbed tryptophan metabolism was related to the decrease in eGFR (49).…”

Section: Discussionsupporting

confidence: 90%

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Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice

et al. 2022

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BackgroundDiabetic kidney disease (DKD), as a serious microvascular complication of diabetes, has limted treatment options. It is reported that the Sacubitril/Valsartan (Sac/Val) can improve kidney function, and the disordered gut microbiota and part of its metabolites are related to the development of DKD. Therefore, we aim to explore whether the effect of Sac/Val on DKD is associated with the gut microbiota and related plasma metabolic profiles.MethodsMale C57BL/6J mice were randomly divided into 3 groups: Con group (n = 5), DKD group (n = 6), and Sac/Val group (n = 6) . Sac/Val group was treated with Sac/Val solution. The intervention was given once every 2 days for 6 weeks. We measured the blood glucose and urine protein level of mice at different times. We then collected samples at the end of experiment for the 16s rRNA gene sequencing analysis and the untargeted plasma metabonomic analysis.ResultsWe found that the plasma creatinine concentration of DKD-group mice was significantly higher than that of Con-group mice, whereas it was reduced after the Sac/Val treatment. Compared with DKD mice, Sac/Val treatment could decrease the expression of indicators related to EndMT and renal fibrosis like vimentin, collagen IV and fibronectin in kidney. According to the criteria of LDA ≥ 2.5 and p<0.05, LefSe analysis of gut microbiota identified 13 biomarkers in Con group, and 33 biomarkers in DKD group, mainly including Prevotella, Escherichia_Shigella and Christensenellaceae_R_7_group, etc. For the Sac/Val group, there were 21 biomarkers, such as Bacteroides, Rikenellaceae_RC9_gut_group, Parabacteroides, Lactobacillus, etc. Plasma metabolomics analysis identified a total of 648 metabolites, and 167 important differential metabolites were screened among groups. KEGG pathway of tryptophan metabolism: M and bile secretion: OS had the highest significance of enrichment.ConclusionsSac/Val improves the renal function of DKD mice by inhibiting renal fibrosis. This drug can also regulate gut microbiota in DKD mice.

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Section: Discussionsupporting

confidence: 90%

“…Tryptophan metabolism was more active in DKD and En groups, which further validates previous reports (23,49). Disturbed tryptophan metabolism was related to the decrease in eGFR (49). Tryptophan can produce kynurenine, which can be further metabolized into kynurenic acid (Kyna) and other substances (50).…”

Section: Discussionsupporting

confidence: 86%

Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice

et al. 2022

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“…It is noteworthy that N-(indol-3-ylacetyl) glutamine had been previously reported as urine metabolite associated with metabolic syndrome 23 and diabetes. 44 Two other indole metabolites presenting VIP values 0.72 and 0.58 were indole-3-carbaldehyde (fold change 3.89, p 0.048) and indole-3-carboxylic acid (fold change 2.13, p 0.009), respectively (Table 3, Figure 2). Since the two compounds are oxidation products of 3IAA, 30 the pro-oxidative conditions accompanying metabolic syndrome might influence their increased production as compared to the control group.…”

Section: Discussionmentioning

confidence: 98%

“…It is noteworthy that N-(indol-3-ylacetyl) glutamine had been previously reported as urine metabolite associated with metabolic syndrome 23 and diabetes. 44…”

Section: Discussionmentioning

confidence: 99%

Liquid chromatography-mass spectrometry untargeted metabolomics reveals increased levels of tryptophan indole metabolites in urine of metabolic syndrome patients

Esperanza

Wróbel

Ojeda

et al. 2020

Eur J Mass Spectrom (Chichester)

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Metabolic syndrome (MetS) is a multifactor condition predisposing for diabetes, cardiovascular diseases and other degenerative disorders. Although several diagnostic criteria have been established, none of them is specific and there is a call for better pathophysiological explanation of MetS and for the discovery of molecular biomarkers. Phenotype characterization at metabolome level might be useful for both purposes. To this end, our aim was to perform comparative untargeted metabolomics of urines from MetS patients and from the control group. The study participants included 52 diagnosticated and 50 healthy individuals from Leon city in central Mexico; 23 anthropometric and clinical parameters were measured and submitted to Principal Component Analysis (PCA). The obtained PCA model allowed us for selection of 11 MetS patients and 13 control subjects, correspondingly representative for each of the two groups (clearly separated in PCA). The first morning urines from these subjects were ambulatory collected and, after methanol extraction and acidification, were submitted to capillary liquid chromatography-high resolution mass spectrometry (LC-HRMS). The obtained data were analyzed on MetaboScape® platform (Bruker Daltonics). Specifically, t-test applied to LC-HRMS data revealed several ions presenting at least 3-fold higher intensities in MetS with respect to the control samples (p < 0.05). Data analysis and complementary experiments yielded the identification of the following metabolites: indole-3-acetic acid, indole-3-acetic acid-O-glucuronide, N-(indol-3-ylacetyl) glutamine, indole-3-carbaldehyde and hydroxyhexanoycarnitine. Additionally, indole-3-carboxylic acid was annotated with 2.13-fold higher abundance in MetS patients. To assess the contribution of individual metabolites in the difference between two groups of subjects, partial least square discriminant analysis was performed for LC-HRMS data and the obtained values of variable importance in projection (VIP), confirmed the association of six above mentioned compounds with MetS. Overall, this study provides direct evidence on the disturbed catabolism of tryptophan in metabolic syndrome.

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“…[12] Metabonomics, combined with pattern recognition, expert system, and other analysis methods, represents one of the best methods to discover potential active ingredients at present. [13] The development of network pharmacology is based on the deepening understanding of the interaction between molecules and proteins. Hence, network pharmacology has great potential for understanding the occurrence and development of diseases, TCM syndromes, and the mechanisms underlying treatment of diseases with TCM.…”

Section: Introductionmentioning

confidence: 99%

Uncovering anti-influenza mechanism of Ophiocordyceps sinensis using network pharmacology, molecular pharmacology, and metabolomics

Zhou,

Wang,

Sun

et al. 2023

Medicine

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Ophiocordyceps sinensis is a precious Chinese traditional herb with a long medicinal history. This study used UPLC-MS metabolomics to explore and compare the metabolic profiles of the stroma (OSBSz), sclerotium (OSBSh), and mycelium (OSBS) of O sinensis to analyze their differential metabolites and identified potential active components. Then combined with network pharmacology and molecular docking to explore the mechanism of differential metabolites with anti-influenza properties. The results indicate that the stroma, sclerotium, and mycelium showed significant differences in metabolites. The key pathways for differential metabolites were butanoate metabolism, thiamin metabolism, alanine, aspartate and glutamate metabolism, citrate cycle, and arginine biosynthesis. Protein-protein interaction analysis identified potential targets, including SRC, RHOA, HSP90AA1, VEGFA, ITGB1, PRKCA, and ITGA1, and the key protective pathways in-volved PI3K-Akt, HIF-1, influenza A, and Coronavirus disease 2019. The molecular docking results showed that the core metabolite D-(−)-glutamine has high binding affinity with SRC, RHOA, and EGFR, re-flecting the multi-component and multi-target network system of O sinensis. In short, the combination of metabonomics, network pharmacology and macromolecular docking technology provides a new way to explore the anti-influenza research of O sinensis. This is undoubtedly an important theoretical support for the clinical application of O sinensis in the future.

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Effects of Bailing capsule on diabetic nephropathy based on UPLC-MS urine metabolomics

Abstract: UPLC-MS-based metabolomics along with pattern recognition was applied to explore the metabolic alteration of diabetic nephropathy and therapeutic mechanisms of Bailing capsule.

Cited by 8 publications

References 35 publications

Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice

Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice

Liquid chromatography-mass spectrometry untargeted metabolomics reveals increased levels of tryptophan indole metabolites in urine of metabolic syndrome patients

Uncovering anti-influenza mechanism of Ophiocordyceps sinensis using network pharmacology, molecular pharmacology, and metabolomics

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