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The network of gastric ulcer. Note: Yellow points in the fig represent biomarkers that have significant difference between the metabolites. The multi-point and multi-pathway involve in combined effect to the formation and healing of gastric ulcer. doi:10.1371/journal.pone.0082499.g008
Source publication
Metabolomics, the systematic analysis of potential metabolites in a biological specimen, has been increasingly applied to discovering biomarkers, identifying perturbed pathways, measuring therapeutic targets, and discovering new drugs. By analyzing and verifying the significant difference in metabolic profiles and changes of metabolite biomarkers,...
Contexts in source publication
Context 1
... changes in the relative concentrations of target metabolites identified in different groups was analyzed, we have found that content of these key markers closer to normal group. The results indicate the mechanism for the treatment of gastric ulcers may be achieved through the regulation of these significantly markers and their interaction like Fig. 8. For example, stearic acid which called 17FA, has relationship with thapsic acid though the protein Fabp1 (fatty acid-binding protein 1). The network not only indicates the interaction between biomarkers, but also provides information of potential protein, genes, enzymes and biological processes. It contributes to the discovery of ...
Context 2
... confirm our metabolomics findings, we need some molecular data, so we identified 5 mRNAs which are related to the 4 potential biomarkers and 2 metabolic pathways with RT- PCR. Sphingolipid metabolism, including S1Pr1, S1Pr3 and SphK1 were examined as showed in Fig. 8. The results are summarized in Fig. 9. The mRNA level of S1Pr1, SIPr3 and SphK1 were significantly upregulated in the model group, the expression levels were 5.21, 2.54, 6.57 times compared to the control group, which was in agreement with our previous findings and data. After CA treatment, the expression levels of S1Pr1, S1Pr3 and ...
Context 3
... enables us to better understand pathological processes and substance metabolic pathways. We believe that the biomarker and pathway analyses have great potential to explore and clarify the therapeutic action of TCM. In current study, we have characterized biomarker interaction networks involve pro- teins, genes, enzymes and bioprocess as shown in Fig. 8. S1P act extracellularly as a ligand for its specific receptors-S1PRs, is now recognized as regulator of many physiological and pathophysiological processes, including inflammatory disorders, such as rheumatoid arthritis, inflammatory bowel disease, and sepsis [27,28]. Inflammation that occurs in the mucosal of gastrointestinal tract, ...
Similar publications
Limonin has been found to possess significant anti-inflammatory properties in animal tests and with, human cells, however, its precise metabolism mechanism has not been well explored. The aim of this study was to investigate the anti-inflammatory effects of limonin in a nonbacterial prostatitis (NBP) animal model. Global metabolite profiling was pe...
Limonin has been found to possess significant anti-inflammatory properties in animal tests and with, human cells, however, its precise metabolism mechanism has not been well explored. The aim of this study was to investigate the anti-inflammatory effects of limonin in a nonbacterial prostatitis (NBP) animal model. Global metabolite profiling was pe...
Citations
... The perturbation in stearic acid level in ethanol model rats in this study is in accordance with previous report of Gupta et al. (2021) revealing the role of stearic acid in fatty acids metabolism disorder and rehabilitation of peptic ulcers. The disruption in stearic acid level causes fatty acid metabolism complications, which leads to an increase in inflammatory responses and mitochondrial dysfunction, as well as the development of ulcers (Tianjiao et al. 2014). ...
Context:
Gastric ulcer (GU) a widely distributed ailment is associated with many causes, including alcohol consumption.
Materials and methods:
Chemical profiling of Symphyotrichum squamatum ethanol extract (SSEE) was established via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) and employed in a silver nano-formulation (SSEE-N-Ag). SSEE and SSEE-N-Ag antiulcer activities were estimated against ethanol-induced rats by biochemical, histological, and metabolomics assessments. Reduced glutathione, total antioxidant capacity and prostaglandin E2 levels and gastric mucosa histopathological examination were analyzed. The rats' metabolome changing alongside action pathways were elucidated via metabolite profile coupled to multivariate data analysis.
Results:
UPLC-MS profiling of SSEE identified 75 components belonging to various classes. Compared with control, EtOH-treated rats showed decreased of tissue GSH, TAC and PGE2 by 62.32%, 51.85% and 47.03% respectively. SSEE and SSEE-N-Ag administration mitigated biochemical and histopathological alterations. Serum metabolomics analysis revealed for changes in several low molecular weight metabolites with ulcer development. These metabolites levels were restored to normal post-administration of SSEE-N-Ag. SSEE-N-Ag as mediated via modulating numerous metabolic pathways such as lipids, pyrimidine, energy metabolism and phosphatidylinositol signaling. This study provides novel insight for metabolic mechanisms underlying gastric ulcer relieving effect.
Conclusion:
Present results revealed potential antiulcer effect of SSEE and SSEE-N-Ag by decreasing ulcer-associated syndromes, supporting their anti-ulcerogenic action.
... In the case of gastric ulcer, its molecular mechanism has been documented; however, more investigations are required to fully understand different aspects of this disorder (4). There is evidence that related biomarkers for gastric ulcer are investigated by omics methods such as metabolomics (5). Gastric ulcer compared to gastric cancer is evaluated by proteomics (6). ...
Aim:
The current study explored the crucial dysregulate proteins and biochemical pathways in gastric ulcer as its main aim.
Background:
Gastric ulcer as an acid-related gastrointestinal disease is known as one of the most public gastrointestinal disorders.
Methods:
A total of 100 proteins from STRING database were analyzed by Cytoscape and its applications to find the central proteins and the related biochemical pathways. Action map analysis was applied to explore regulatory relationships between the critical proteins.
Results:
Network analysis and gene ontology revealed that IL6, ALB, TNF, INS, IL1B, IL10, TP53, CXCL8, and PTGS2 are the highlighted proteins related to gastric ulcer. Six clusters of biochemical pathways, namely "response to external stimulus," "multicellular organismal process," "regulation of biological quality," "cellular response to stimulus," "cellular response to chemical stimulus," and "transport" were identified as the dysregulated pathway in patients.
Conclusion:
Down-regulation of TP53 by IL2, PTGS2, and TNF seems to be a main process occurring in gastric ulcer patients.
... In the light of the pattern recognition analysis mentioned hereinbefore, the significant metabolites were labeled as the metabolic biomarkers in the Con, IMQ, and ESW groups. After that, we executed metabolic pathway analysis using the online tool MetaboAnalyst 3.0 and Human Metabolome Database to evaluate the significant variations among different groups (Tianjiao et al., 2014). ...
Pithecellobium clypearia Benth. (accepted name: Archidendron clypearia (Jack) I.C.Nielsen; Mimosaceae), a popular traditional Chinese medicine, has a significant anti-inflammatory effect. The crude water extract of the aerial part of P. clypearia has been clinically applied to treat upper respiratory tract infections, acute gastroenteritis, laryngitis, and pharyngitis. However, the therapeutic mechanism of ethanol fraction of water extract (ESW) of P. clypearia to treat psoriasis should be complemented. The aim of our research was to clarify the protective effects of ESW from P. clypearia against psoriasis-like skin inflammation induced by imiquimod (IMQ) in mice with efficacy indexes and target tissue (spleen and serum) metabolomics. The ingredient of ESW was analyzed by ultrahigh-performance liquid chromatography combined with tandem mass spectrometry (UHPLC-MS/MS) method. The imiquimod-induced psoriatic mouse model was employed to investigate the effect of ESW against psoriasis, where the treatment method was implemented for 6 days both topically (Gel at 5%) and orally (at 2.4 g/kg p.o.). Traditional pharmacodynamic indicators (phenotypic characteristics, psoriasis area and severity index (PASI) score, H&E staining, immunohistochemical staining, the thickness of epidermis, body weight change, and spleen index) were conducted to appraise the efficacy of ESW. Furthermore, a gas chromatography-mass spectrometer (GC-MS) coupled with multivariate analysis was integrated and applied to obtain serum and spleen metabolic profiles for clarifying metabolic regulatory mechanisms of ESW. The current study illustrated that ESW is composed mainly of gallic acid, ethyl gallate, quercitin, 7-O-galloyltricetiflavan, quercetin, and myricetin by UHPLC-MS/MS analysis. ESW could distinctly improve IMQ-induced psoriasis in mouse through reducing PASI score, alleviating tissue damage, restoring spleen index, and inhibiting proliferating cell nuclear antigen (PCNA) expression in psoriasis-like skin tissue. From the metabolomics study, 23 markers with significant changes are involved in eight main pathways in spleen and serum samples, including linoleic acid metabolism and glycine, serine, and threonine metabolism. The current study showed that ESW had obvious antipsoriasis effects on IMQ-induced psoriasis in mice, which might be attributed to regulating the dysfunction of differential biomarkers and related pathways. In summary, ESW of P. clypearia showed a favourable therapeutic effect on IMQ-induced psoriasis, and metabolomics provided insights into the mechanisms of ESW to the treatment of psoriasis.
... In addition, as per the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 14.5 million Americans and about 350,000 new PUD cases are diagnosed with PUD every year (Chai, 2011). Among various endogenous and exogenous stress factors, smoking, nutritional deficiencies, gastric acid, dyspepsia, prolonged intake of non-steroidal anti-inflammatory drug use (NSAIDs), and alcohol are the factors associated with peptic ulcers (Li et al., 2014). In 70-90% of cases, peptic ulcers are found to be associated with spiral-shaped Helicobacter pylori bacteria that reside in the acidic environment of the stomach (Ali, 2013). ...
... Stearic acid (FC, 6.042) and valeric acid (FC, 3.857) were the most elevated saturated fatty acids, while arachidonic acid (FC, −0.645) was the most depleted one. Li et al. (2014) reported the role of stearic acid (also known as Octadecanoic acid) in fatty acid metabolism disorder and rehabilitation of peptic ulcers. Stearic acid promotes ulcer formation by increasing the inflammatory response and mitochondrial dysfunction. ...
Helicobacter pylori infection has been significantly linked to Peptic Ulcer Disease and Gastric Cancer. Metabolomic fingerprinting may offer a principal way of early diagnosis and to understand the molecular mechanism of H. pylori-induced pathogenicity. The rationale of the study is to explore the underlying distinct metabolic mechanisms of H. pylori-induced PUD and to identify potential biomarkers for disease diagnosis and associated risks using Gas chromatography/mass spectrometry. GC/MS-based analytical method was used to compare metabolic profiles of healthy controls (N = 20) and peptic ulcer patients (N = 45). Acquired metabolomic data were analyzed by constructing a diagnostic model using principal component analysis and a non-parametric two-tailed paired Wilcoxon analysis to identify disease-specific metabolic biomarkers. A total of 75 low-molecular-weight endogenous metabolites were detected during comparative metabolomic analysis of PUD vs. healthy gut tissues, among which 16 metabolites are being proposed to be diagnostic markers of Human PUD. Perturbations related to amino acids, carbohydrates, fatty acids, organic acids, and sterol metabolism were significantly revealed during this differential metabolomic profiling. Results convincingly suggest that metabolic profiles can contribute immensely in early diagnosis of the disease and understanding molecular mechanisms of disease progression for predicting novel drug targets for prophylactic and anaphylactic measures.
... The method has been confirmed to be precise, accurate, and sensitive enough for untargeted analysis. 30,31 The present study is the first application of MPP technology in determining honey maturity. We analyzed 18 batches of honey samples collected from three different hives. ...
Harvesting uncapped immature honey (IMH) followed by dehydration is a typical counterfeit honey production process, but the differences between IMH and capped mature honey (MH) have not been well described previously. In this study, MH and IMH from Apis mellifera colonies during the same rapeseed flower season were compared. MH was found to have lower water content, lower acidity, and higher fructose content. High-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry-based untargeted metabolomic analysis indicated that MH had a distinct metabolite composition to IMH. Targeted metabolomic analysis on 20 major polyphenolic constituents showed higher accumulation in MH. MH had greater bacteriostatic effect and stronger free radical scavenging effect. While both the honeys mitigated cell damage caused by H2O2, the effective dosage of IMH was higher and its inducing effect on the antioxidant gene expression was weaker. Overall, MH was shown to be of better quality than IMH not only because of its richer polyphenolic composition but also because of its stronger biological activity.
... Brassica rapa L., a famous traditional Chinese herb, displays wide spectrum bioactivity, including antioxidant [45], anticancer, hypoglycemic, anti-hypoxia activity [46], bacteriostatic and anti-fatigue effects. Two novel indole-alkaloid compounds ( Fig. 2a & 2b) with potent anticancer activity were isolated from the rizhome of Brassica rapa L. [47] and the dry tuberous root of Corydalis yanhusuo W. T. Wang [48][49][50][51], and the two compounds can inhibit the growth of renal cancer RC-2 cells via increasing p53 expression; treatment of human renal cancer RC-2 cells with the compound resulted in the up-regulation of wild-type p53 mRNA expression significantly. Ecteinascidins, isolated from the marine tunicate Ecteinascidia turbinata, displayed potent anticancer activity toward several cancer cells [52]. ...
Background
In recent years, many novel alkaloids with anticancer activity are found in China, and some of them are promising for developing anticancer agents.
Objective
This review aims to provide a comprehensive overview of the information about alkaloid anticancer agents disclosed in Chinese patents, and discuss their potential to be developed as anticancer drugs used clinically.
Methods
Anticancer alkaloids disclosed in Chinese patents in recent 5 years were presented according to their mode of actions. Their study results published on PubMed, and SciDirect data bases were presented.
Results
More than one hundred anticancer alkaloids were disclosed in Chinese patents and their mode of action referred to arresting cell cycle, inhibiting protein kinases, affecting DNA synthesis and p53 expression etc.
Conclusion
Many newly found alkaloids displayed potent anticancer activity both in vitro and in vivo, and some of the anticancer alkaloids acted as protein kinase inhibitors or CDK inhibitors possess potential for developing as novel anticancer agents.
... Eluted samples were injected in 6560 Ion Mobility QTOF-LC/MS (Agilent Technologies, USA) for analysis (Joshi et al. 2018). MPP software was used to generate molecular feature files from raw data which are processed further for quantitative analysis (Tianjiao et al. 2014). One-way ANOVA followed by Benjamini-Hochberg correction was used to examine the statistically significant differences among mass intensities of metabolites. ...
Main conclusion
Comparative proteomics and metabolomics study of juvenile green, light purple and dark purple leaf to identify key proteins and metabolites that putatively govern color transition in Camellia sinensis.
Abstract
Color transition from juvenile green to dark purple leaf in Camellia sinensis is a complex process and thought to be regulated by an intricate balance of genes, proteins and metabolites expression. A molecular-level understanding of proteins and metabolites expression is needed to define metabolic process underpinning color transition in C. sinensis. Here, purple leaf growth of C. sinensis cultivar was divided into three developmental stages viz. juvenile green (JG), light purple (LP) and dark purple (DP) leaf. Scanning electron microscope (SEM) analysis revealed a clear morphological variation such as cell size, shape and texture as tea leaf undergoing color transition. Proteomic and metabolomic analyses displayed the temporal changes in proteins and metabolites that occur in color transition process. In total, 211 differentially expressed proteins (DEPs) were identified presumably involved in secondary metabolic processes particularly, flavonoids/anthocyanin biosynthesis, phytohormone regulation, carbon and nitrogen assimilation and photosynthesis, among others. Subcellular localization of three candidate proteins was further evaluated by their transient expression in planta. Interactome study revealed that proteins involved in primary metabolism, precursor metabolite, photosynthesis, phytohormones, transcription factor and anthocyanin biosynthesis were found to be interact directly or indirectly and thus, regulate color transition from JG to DP leaf. The present study not only corroborated earlier findings but also identified novel proteins and metabolites that putatively govern color transition in C. sinensis. These findings provide a platform for future studies that may be utilized for metabolic engineering/molecular breeding in an effort to develop more desirable traits.
... Agilent Technologies, Inc.). Finally, principal components analysis (PCA), the cluster analysis used for multivariate analysis and one-way analysis of variance (ANOVA) used for expressing the significance of data were performed with Mass Profiler Professional (MPP) 12.6 software (Agilent Technologies, Inc.), as described previously (26). The metabolites were preliminarily identified in METLIN (https://metlin.scripps. ...
Glycyrrhiza, commonly known as licorice, is a herbal medicine that has been used for thousands of years. Licorice contains multiple flavonoids, which possess a variety of biological activities. On the basis of the anti-inflammatory effects of licorice flavonoids, the potential mechanism of action was investigated via a plasma metabolomics approach. A total of 9 differential endogenous metabolites associated with the therapeutic effect of licorice flavonoids were identified, including linoleic acid, sphingosine, tryptophanamide, corticosterone and leukotriene B4. Besides classical arachidonic acid metabolism, metabolism of sphingolipids, tryptophan and fatty acids, phospholipids synthesis, and other pathways were also involved. The multi-pathway integrated adjustment mechanism of licorice flavonoid action may reduce side effects in patients, along with any anti-inflammatory functions, which provides a foundation for identifying and developing novel, high-potential natural drugs with fewer side effects for clinical application.
... Methanol and water are widely accepted extraction solvent combination due to hydrophilic nature of nucleosides. [31] The calibration curves were plotted against the peak area versus the concentration of all the analyte detected by UV. ...
... High yielding ability in water make it to be the best solvent system. [31] Ultrasonic extraction and reflux were proved to be more efficient and faster extraction method. [33] The ultrasonic sound waves facilitate the solvent extraction more effectively than other methods. ...
A fast, reliable and reproducible UHPLC-IMS method was developed and validated for simultaneous determination of eight nucleosides (adenine, adenosine, cordycepin, guanosine, inosine, thymidine, thymine and uracil) in natural Ophiocordyceps sinensis. Present study was conducted to determine the marker nucleoside contents in low quantities using the developed method. Methanol and water in combination were used as extraction solvents due to hydrophilic nature of nucleosides. These nucleosides showed good linearity (r²>0.99), LOD (0.28–0.97ng/mL), LOQ (0.79–3.20 ng/mL), recoveries (88.3 and 103.2%), reproducibility, stability and intra- and inter-day precision (<2.87%). Method was validated using three samples of natural Ophiocordyceps collected from different geographical region. PCA analysis depicted that adenine, adenosine, guanine, guanosine, uracil and uridine were major components contributing to total variance. Highest nucleosides content (5124 µg/g) was detected in STD-1. The presence of cordycepin, an important marker compound was identified for first time using ion mobility mass spectrometry (IMMS) technique. Metabolomics approach resulted 18, 12 and 9 metabolites in three samples (STD-1, STD-II and STD-III, respectively) using METLIN database which opened the new avenues to identify and explore more novel biomarkers in Ophiocordyceps. We anticipate that these methods may be applied to verify/certification of Ophiocordyceps containing marker nucleosides for their dietary intake.
... Secondly, the resulting feature files were processed by the analysis of PCA and PLS-DA in MPP software. The biomarkers with significant changes in the groups were determined by ID Browser features of MPP (Li et al. 2014;Lin et al. 2012;Zhu et al. 2013). And all data were expressed as the mean ± standard deviation (SD) of three independent experiments. ...
As one of the major active components of Qizhiweitong (QZWT) prescription, corydalis alkaloid (CA) has been reported to have noticeable effect of anti-inflammation in pharmacological studies. However, the anti-inflammatory function and potential mechanism of CA in anti-inflammation remain to be clarified. Hence, the aim of this study was to investigate the anti-inflammation efficacy and potential mechanism of CA in anti-inflammation by metabonomic approach coupled with related gene analyzes in vivo and in vitro. Mice acute inflammation was induced by subcutaneous injection of formalin in hind paws, and evaluated the anti-inflammatory effect of CA via detecting the index of paw edema. The results indicated that CA has an anti-inflammatory effect on mice through alleviating the paw edema significantly. Moreover, metabolic profiling was performed by high performance liquid chromatography quadrupole-time-of-flight mass spectrometer (HPLC-QTOF-MS) combined with multivariate data analysis, such as principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). Thirteen metabolic targets (including lysophosphatidylcholine (LysoPC), choline, arachidonic acid, phosphodimethylethanolamine) and related pathways of the cholinergic anti-inflammatory and arachidonic acid (AA) metabolism were identified, Meanwhile, the relevant target genes, like iNOS, NF-κB, TNF-α, were detected and verified in vitro. The results indicated that CA has a good pharmacological effect of anti-inflammation through regulating multiple disordered targets and metabolic networks, which provides a theoretical basis for further research on CA. Furthermore, there is a great potential for the development of CA to be a new anti-inflammatory drug with high effective activities, little side effects and weak drug resistance.
