scholarly journals Identification of Metabolites and Metabolic Pathways Related to Treatment with Bufei Yishen Formula in a Rat COPD Model Using HPLC Q-TOF/MS

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Liping Yang ◽  
Jiansheng Li ◽  
Ya Li ◽  
Yange Tian ◽  
Suyun Li ◽  
...  

As a traditional Chinese medicine, Bufei Yishen Formula (BYF) is widely used in China as an effective treatment for chronic obstructive pulmonary disease (COPD). Because of the component complexity and multiple activities of Chinese herbs, the mechanism whereby BYF affects COPD is not yet fully understood. Herein, pulmonary function experiments and histomorphological assessments were used to evaluate the curative effect of BYF, which showed that BYF had an effect on COPD. Additionally, a high performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC QTOF/MS) metabonomics method was used to analyze the mechanism of the actions of BYF on rats with COPD induced by a combination of bacteria and smoking. Partial least squares discriminate analysis (PLS-DA) was used to screen biomarkers related to BYF treatment. Candidate biomarkers were selected and pathways analysis of these metabolites showed that three types of metabolic pathways (unsaturated fatty acid metabolism-related pathways, phenylalanine metabolism-related pathways, and phospholipid metabolism-related pathways) were associated with BYF treatment. Importantly, arachidonic acid and related metabolic pathways might be useful targets for novel COPD therapies.

2020 ◽  
Author(s):  
Ying Dong ◽  
Xiaowei Liu ◽  
Shenglong Zhao ◽  
Yuanyuan Zheng ◽  
Chunbo Li ◽  
...  

Abstract Background: Preeclampsia (PE) is one of the main causes of maternal and fetal morbidity and mortality worldwide. This study was aimed to explore the potential metabolic alterations in women diagnosed with PE and reveal the underlying pathogenesis of disease.Methods: Healthy pregnant women and patients diagnosed with PE were recruited from August 2017 to February 2018. The metabolomic analysis of serum (n=90) and placenta (n=9) samples collected from the two groups were performed with the high performance liquid chromatography coupled with quadrupole-time-of light mass spectrometry (HPLC-QTOF-MS).Results: In serum, 16 metabolites that were present in different concentrations between the two groups were identified, of which pyroglutamic acid (pGlu), methionine, glutamine and taurocholic acid may be used as potential PE diagnosis biomarkers with the area under ROC curve of 0.901, 0.909, 0.892 and 0.873 respectively. Furthermore, the metabolic pathways analysis with differential metabolites in serum and placenta samples showed that linoleic acid and alpha- linolenic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, D-glutamine/D-glutamate metabolism, phenylalanine metabolism, glutathione (GSH) metabolism and tryptophan metabolism were significantly altered and might be involved in PE pathogenesis.Conclusions: These results showed the altered metabolic pathways could contribute to the pathophysiologic mechanisms of PE.


2020 ◽  
Author(s):  
Ying Dong ◽  
Xiaowei Liu ◽  
Shenglong Zhao ◽  
Yuanyuan Zheng ◽  
Chunbo Li ◽  
...  

Abstract Background: Preeclampsia (PE) is one of the main causes of maternal and fetal morbidity and mortality worldwide. This study was aimed to explore the potential metabolic alterations in women diagnosed with PE and reveal the underlying pathogenesis of disease. Methods; Healthy pregnant women and patients diagnosed with PE were recruited from August 2017 to February 2018. The metabolomic analysis of serum (n=90) and placenta (n=9) samples collected from the two groups were performed with the high performance liquid chromatography coupled with quadrupole-time-of light mass spectrometry (HPLC-QTOF-MS). Results: In serum, 16 metabolites that were present in different concentrations between the two groups were identified, of which pyroglutamic acid (pGlu), methionine, glutamine and taurocholic acid may be used as potential PE diagnosis biomarkers with the area under ROC curve of 0.901, 0.909, 0.892 and 0.873 respectively. Furthermore, the metabolic pathways analysis with differential metabolites in serum and placenta samples showed that linoleic acid and alpha- linolenic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, D-glutamine/D-glutamate metabolism, phenylalanine metabolism, glutathione metabolism and tryptophan metabolism were significantly altered and might be involved in PE pathogenesis. Conclusions: These results showed the altered metabolic pathways could contribute to the pathophysiologic mechanisms of PE.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3314
Author(s):  
Tomasz Kowalczyk ◽  
Joanna Kisluk ◽  
Karolina Pietrowska ◽  
Joanna Godzien ◽  
Miroslaw Kozlowski ◽  
...  

Identification of the NSCLC subtype at an early stage is still quite sophisticated. Metabolomics analysis of tissue and plasma of NSCLC patients may indicate new, and yet unknown, metabolic pathways active in the NSCLC. Our research characterized the metabolomics profile of tissue and plasma of patients with early and advanced NSCLC stage. Samples were subjected to thorough metabolomics analyses using liquid chromatography-mass spectrometry (LC-MS) technique. Tissue and/or plasma samples from 137 NSCLC patients were analyzed. Based on the early stage tissue analysis, more than 200 metabolites differentiating adenocarcinoma (ADC) and squamous cell lung carcinoma (SCC) subtypes as well as normal tissue, were identified. Most of the identified metabolites were amino acids, fatty acids, carnitines, lysoglycerophospholipids, sphingomyelins, plasmalogens and glycerophospholipids. Moreover, metabolites related to N-acyl ethanolamine (NAE) biosynthesis, namely glycerophospho (N-acyl) ethanolamines (GP-NAE), which discriminated early-stage SCC from ADC, have also been identified. On the other hand, the analysis of plasma of chronic obstructive pulmonary disease (COPD) and NSCLC patients allowed exclusion of the metabolites related to the inflammatory state in lungs and the identification of compounds (lysoglycerophospholipids, glycerophospholipids and sphingomyelins) truly characteristic to cancer. Our results, among already known, showed novel, thus far not described, metabolites discriminating NSCLC subtypes, especially in the early stage of cancer. Moreover, the presented results also indicated the activity of new metabolic pathways in NSCLC. Further investigations on the role of NAE biosynthesis pathways in the early stage of NSCLC may reveal new prognostic and diagnostic targets.


2021 ◽  
pp. 153537022110088
Author(s):  
Mingshan Xue ◽  
Yifeng Zeng ◽  
Runpei Lin ◽  
Hui-Qi Qu ◽  
Teng Zhang ◽  
...  

While there is no cure for chronic obstructive pulmonary disease (COPD), its progressive nature and the formidable challenge to manage its symptoms warrant a more extensive study of the pathogenesis and related mechanisms. A new emphasis on COPD study is the change of energy metabolism. For the first time, this study investigated the anaerobic and aerobic energy metabolic pathways in COPD using the metabolomic approach. Metabolomic analysis was used to investigate energy metabolites in 140 COPD patients. The significance of energy metabolism in COPD was comprehensively explored by the Global Initiative for Chronic Obstructive Lung Disease–GOLD grading, acute exacerbation vs. stable phase (either clinical stability or four-week stable phase), age group, smoking index, lung function, and COPD Assessment Test (CAT) score. Through comprehensive evaluation, we found that COPD patients have a significant imbalance in the aerobic and anaerobic energy metabolisms in resting state, and a high tendency of anaerobic energy supply mechanism that correlates positively with disease progression. This study highlighted the significance of anaerobic and low-efficiency energy supply pathways in lung injury and linked it to the energy-inflammation-lung ventilatory function and the motion limitation mechanism in COPD patients, which implies a novel therapeutic direction for this devastating disease.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Haroon Arshad ◽  
Juan Carlos López Alfonso ◽  
Raimo Franke ◽  
Katina Michaelis ◽  
Leonardo Araujo ◽  
...  

Abstract Background There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage. Methods We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n = 29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n = 13) as a clinically important disease control, and 33 age- and sex-matched controls. Results Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and ceramides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also differed qualitatively, e.g. by increases in selected sphingomyelins. We identified highly accurate biomarkers for CAP (AUC ≤ 0.97) and COPD (AUC ≤ 0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC ≤ 0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and differentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers reflect more than merely inflammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change = 2.8, AUC = 0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution. Conclusions The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal differences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yanyan Xu ◽  
Yiwei Zhao ◽  
Jiabin Xie ◽  
Xue Sheng ◽  
Yubo Li ◽  
...  

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.


2001 ◽  
Vol 163 (4) ◽  
pp. 859-864 ◽  
Author(s):  
MARIËLLE P. K. J. ENGELEN ◽  
EMIEL F. M. WOUTERS ◽  
NICOLAAS E. P. DEUTZ ◽  
JOAN D. DOES ◽  
ANNEMIE M. W. J. SCHOLS

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yixin Huang ◽  
Liuhong Shen ◽  
Jing Jiang ◽  
Qipin Xu ◽  
Zhengzhong Luo ◽  
...  

AbstractBovine mammary epithelial cells (bMECs) are the main cells of the dairy cow mammary gland. In addition to their role in milk production, they are effector cells of mammary immunity. However, there is little information about changes in metabolites of bMECs when stimulated by lipopolysaccharide (LPS). This study describes a metabolomics analysis of the LPS-stimulated bMECs to provide a basis for the identification of potential diagnostic screening biomarkers and possible treatments for bovine mammary gland inflammation. In the present study, bMECs were challenged with 500 ng/mL LPS and samples were taken at 0 h, 12 h and 24 h post stimulation. Metabolic changes were investigated using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS) with univariate and multivariate statistical analyses. Clustering and metabolic pathway changes were established by MetaboAnalyst. Sixty-three differential metabolites were identified, including glycerophosphocholine, glycerol-3-phosphate, L-carnitine, L-aspartate, glutathione, prostaglandin G2, α-linolenic acid and linoleic acid. They were mainly involved in eight pathways, including D-glutamine and D-glutamic acid metabolism; linoleic acid metabolism; α-linolenic metabolism; and phospholipid metabolism. The results suggest that bMECs are able to regulate pro-inflammatory, anti-inflammatory, antioxidation and energy-producing related metabolites through lipid, antioxidation and energy metabolism in response to inflammatory stimuli.


Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 291 ◽  
Author(s):  
Joseph Diab ◽  
Terkel Hansen ◽  
Rasmus Goll ◽  
Hans Stenlund ◽  
Einar Jensen ◽  
...  

The onset of ulcerative colitis (UC) is characterized by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host–microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies. This study aims to explore the mucosal metabolomic profile in UC patients, and to define the UC metabolic signature. Treatment- naïve UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopies. Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acyl carnitine, and amino acid profiles. Several pathways were found perturbed according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as tryptophan metabolism) to fatty acid metabolism, namely linoleic and butyrate. These metabolic changes during UC reflect the homeostatic disturbance in the gut, and highlight the importance of system biology approaches to identify key drivers of pathogenesis which prerequisite personalized medicine.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Min Jung Kim ◽  
Da-Hye Lee ◽  
Jiyun Ahn ◽  
Tae-Youl Ha ◽  
Young Jin Jang ◽  
...  

Although classification of an individual’s Sasang constitution is a key step in the prescription of traditional Korean medicine, the classifying process is complex and not objective. Identification of metabolic-based biomarkers could allow the development of a reliable and sensitive classification technique and even therapeutic management. Our pilot study investigated whether metabolites in plasma are characteristic of Sasang constitutions. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolic analysis was conducted against 15 Soyangin (SY), 15 Taeeumin (TE), and 18 Soeumin (SE) individuals, as classified according to the Questionnaire for Sasang Constitution Classification II (QSCC II) and specialist diagnosis. Metabolomics data showed that the TE group was significantly separated from the SY and SE groups. Nine canonical pathways related to constitution; phenylalanine metabolism, aminoacyl-tRNA, tyrosine, and tryptophan biosynthesis were activated in the TE group as compared with the other groups. Similar to the results of the metabolomics analysis, the TE group was also significantly separated from the other two groups by lipidomic analysis. On the other hand, the intensity of lipid metabolites was higher in the SY group than in the other groups. Our findings suggest that the combined analysis of metabolomics and lipidomics can provide useful information for characteristics of Sasang constitutions.


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