scholarly journals Metabolomic Investigation of Synergistic Mechanism for Fangfeng Extract Preventing LPS Induced Neuroinflammation in BV-2 Microglia Cells

2021 ◽  
Vol 11 (17) ◽  
pp. 8155
Author(s):  
Xinliang Zhu ◽  
Xueqi Wang ◽  
Shunbin Zhang ◽  
Xu Li ◽  
Zhengdou Li ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Arachidonic Acid Metabolism ◽  
Disease Treatment ◽  
Protein Targets ◽  
Protective Function ◽  
Related Disease ◽  
Synergistic Mechanism ◽  
Acid Metabolites ◽  
Caffeine Metabolism ◽  
Saposhnikovia Divaricata

The root of Saposhnikovia divaricata (Fangfeng) is commonly used in traditional Chinese medicine (TCM) for headache and neuroinflammation-related disease treatment. The mRNA expression of IL-6 and IL-1β were significantly inhibited after Fangfeng extract (FFE) treatment in LPS-induced BV-2 cells. Metatolome profiling indicated that dopamine, palmitic acid, corticosterone, and eicosapentaenoic acid metabolites could be regulated by FFE for LPS stimulated inflammation responses in BV-2 cells. The disturbed metabolic pathways include caffeine metabolism, mannose type O-glycan biosynthesis, arachidonic acid metabolism, and steroid biosynthesis. This study will enable us to identify potential protein targets and metabolite intermediates for FFE exerting its protective function in BV-2 cells, and it also provided a potential application of Fangfeng in neuroinflammation-related disease treatment.

scholarly journals Metabolic Profiling Revealed Dysregulated Arachidonic Acid Metabolism and Tryptophan Metabolism in the Lungs from Canines with Pacing-induced Heart Failure

2020 ◽  
Author(s):  
Junhan Zhao ◽  
Jing Wang ◽  
Shengwen Yang ◽  
Ran Jing ◽  
Xi Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Arachidonic Acid ◽  
Metabolic Pathways ◽  
Sham Group ◽  
Acid Metabolism ◽  
Congestion Management ◽  
Arachidonic Acid Metabolism ◽  
Tryptophan Metabolism ◽  
Negative Ion ◽  
Metabolic Signatures

Abstract Background: Lung has critical pathophysiological connections to heart and lung congestion presents one of the hallmark features of heart failure (HF). This study aimed to explore the metabolic signatures and disturbances in lungs under HF condition and provide insights on the pathophysiology of the lungs under HF condition from the perspective of metabolism.Methods: In this study, we established a rapid pacing induced HF canine model and applied a comprehensive untargeted metabolomics method to comparatively assessed the metabolomics profiles in the lung tissues from HF group and sham group. Results: Distinct metabolic signatures were identified in the lungs between beagles in HF group and sham group. 81 dysregulated metabolites were identified as differential metabolites (adjusted P <0.05, FC≥2 or≤0.5) in positive ion mode and 80 dysregulated metabolites in negative ion mode, indicating a profound metabolic alteration in the lungs under HF condition. In pathway analysis, arachidonic acid metabolism and tryptophan metabolism were identified as the most significant dysregulated metabolic pathways in the lungs from HF beagles.Conclusions: In this study, we identified profound metabolic variation and dysregulated metabolic pathways, which may deepen our understanding on the pathophysiology of the lungs under HF condition from the perspective of metabolism and open new avenues in lung congestion management in HF.

scholarly journals Level of Arachidonic Acid and State of Peroxidation Processes in Patients with Aspirin-Intolerant Polypous Rhinosinusitis

2016 ◽  
Vol 23 (4) ◽  
pp. 2016410
Author(s):  
Ivanna Koshel
Keyword(s):  
Arachidonic Acid ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Serum Proteins ◽  
Arachidonic Acid Metabolism ◽  
Oxidative Modification ◽  
Key Enzyme ◽  
Protein Peroxidation ◽  
Genetic Block ◽  
Peroxidation Processes

The main peculiarity of aspirin-intolerant polypous rhinosinusitis pathogenesis is the presence of “genetic block” of constitutive cyclooxygenase being the key enzyme of the arachidonic acid metabolism. It justifies the necessity of studying its metabolic peculiarities.The objective of the research was to determine the level of arachidonic acid as well as the state of lipid and protein peroxidation processes in patients with aspirin-intolerant polypous rhinosinusitis.Materials and methods. The levels of arachidonic acid, malondialdehyde and oxidative modification of serum proteins were studied in 20 patients with aspirin-intolerant polypous rhinosinusitis and 7 healthy individuals.Results. Significantly elevated levels of arachidonic levels were observed. The search for alternative metabolic pathways stimulated lipid and protein peroxidation processes and led to the increase in the levels of malondialdehyde and oxidative modification of serum proteins. The peculiarities of biochemical changes indicated pro-inflammatory orientation of lipid metabolism.Conclusions. The obtained data confirmed the hypothesis of “genetic block” of the arachidonic acid metabolism as the main pathogenetic component of aspirin-intolerant polypous rhinosinusitis and allowed us to clearly interpret biochemical picture of the disease.

Metabolomic Signature of Patients With Narcolepsy

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013128
Author(s):  
Dauvilliers Yves ◽  
Lucie Barateau ◽  
Benita Middleton ◽  
Daan Van Der Veen ◽  
Debra J Skene
Keyword(s):  
Arachidonic Acid ◽  
Metabolic Pathways ◽  
Slow Wave Sleep ◽  
Arachidonic Acid Metabolism ◽  
Metabolic Phenotype ◽  
Metabolic Disturbances ◽  
Brain Disorder ◽  
Metabolite Concentrations ◽  
Obese Subjects

Background and Objective:Narcolepsy type 1 (NT1) is an orphan brain disorder caused by the irreversible destruction of orexin neurons. Metabolic disturbances are common in patients with NT1 who have a body mass index (BMI) 10-20% higher than the general population, with one third being obese (BMI>30 kg/m2). Besides the destruction of orexin neurons in NT1, the metabolic alterations in obese and non-obese patients with narcolepsy type 1 remain unknown. The aim of the study was to identify possible differences in plasma metabolic profiles between patients with NT1 and controls as a function of their BMI status.Methods:We used a targeted liquid chromatography-mass spectrometry metabolomics approach to measure 141 circulating, low molecular weight metabolites in drug-free fasted plasma samples from 117 NT1 patients (including 41 obese subjects) compared with 116 BMI-matched controls (including 57 obese subjects).Results:Common metabolites driving the difference between NT1 and controls, irrespective of BMI, were identified, namely sarcosine, glutamate, nonaylcarnitine (C9), 5 long chain lysophosphatidylcholine acyls, one sphingolipid, 12 phosphatidylcholine diacyls and 11 phosphatidylcholine acyl-akyls, all showing increased concentrations in NT1. Metabolite concentrations significantly affected by NT1 (n = 42) and BMI category (n = 40) showed little overlap (n = 5). Quantitative enrichment analysis revealed common metabolic pathways that were implicated in the NT1/control differences, in both normal BMI and obese comparisons, namely glycine and serine, arachidonic acid, and tryptophan metabolisms. The metabolites driving these differences were glutamate, sarcosine and ornithine (glycine and serine metabolism), glutamate and PC aa C34:4 (arachidonic acid metabolism) and glutamate, serotonin and tryptophan (tryptophan metabolism). Linear metabolite-endophenotype regression analyses highlight that as part of the NT1 metabolic phenotype, most of the relationships between the sleep parameters (i.e. slow wave sleep duration, sleep latency and periodic leg movement) and metabolite concentrations seen in the controls were lost.Discussion:These results represented the most comprehensive metabolic profiling of patients with NT1 as a function of BMI and propose some metabolic diagnostic biomarkers for NT1, namely glutamate, sarcosine, serotonin, tryptophan, nonaylcarnitine and some phosphatidylcholines. The metabolic pathways identified offer, if confirmed, possible targets for treatment of obesity in NT1.Classification of Evidence:This study provides Class II evidence that a distinct metabolic profile can differentiate patients with Narcolepsy Type 1 from patients without the disorder.

scholarly journals Changes in hepatic metabolic profile during the evolution of STZ-induced diabetic rats via an 1H NMR-based metabonomic investigation

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Minjiang Chen ◽  
Hong Zheng ◽  
Min Xu ◽  
Liangcai Zhao ◽  
Qianqian Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
1H Nmr ◽  
Metabolic Pathways ◽  
Metabolic Profile ◽  
Diabetic Rats ◽  
Proton Nuclear Magnetic Resonance ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Discriminate Analysis ◽  
Protective Function

Abstract Background: The present study aimed to explore the changes in the hepatic metabolic profile during the evolution of diabetes mellitus (DM) and verify the key metabolic pathways. Methods: Liver samples were collected from diabetic rats induced by streptozotocin (STZ) and rats in the control group at 1, 5, and 9 weeks after STZ administration. Proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabolomics was used to examine the metabolic changes during the evolution of DM, and partial least squares-discriminate analysis (PLS-DA) was performed to identify the key metabolites. Results: We identified 40 metabolites in the 1H NMR spectra, and 11 metabolites were further selected by PLS-DA model. The levels of α-glucose and β-glucose, which are two energy-related metabolites, gradually increased over time in the DM rats, and were significantly greater than those of the control rats at the three-time points. The levels of choline, betaine, and methionine decreased in the DM livers, indicating that the protective function in response to liver injury may be undermined by hyperglycemia. The levels of the other amino acids (leucine, alanine, glycine, tyrosine, and phenylalanine) were significantly less than those of the control group during DM development. Conclusions: Our results suggested that the hepatic metabolic pathways of glucose, choline-betaine-methionine, and amino acids were disturbed during the evolution of diabetes, and that choline-betaine-methionine metabolism may play a key role.

Angiotensin II-induced relaxation of fowl aorta

1988 ◽  
Vol 255 (4) ◽  
pp. R591-R599 ◽  
Author(s):  
K. Yamaguchi ◽  
H. Nishimura
Keyword(s):  
Arachidonic Acid ◽  
Angiotensin Ii ◽  
Arachidonic Acid Metabolism ◽  
Isometric Tension ◽  
Eicosatetraenoic Acid ◽  
Ang Ii ◽  
Acid Metabolites ◽  
Relaxation Responses ◽  
Underlying Mechanisms ◽  
Dose Dependent

Angiotensin II (ANG II) decreases blood pressure of fowl. To characterize the vasodilating action of ANG II and its underlying mechanisms, we examined the effect of [Asp1, Val5]ANG II (fowl ANG II) on isometric tension of fowl aortic rings. [Val5]ANG II (10(-8) to 10(-5) M) produced rapid, reversible, dose-dependent relaxation of aortas precontracted with phenylephrine. [Sar1,Ile8]ANG II blocked ANG II-induced relaxation; propranolol, atropine, methysergid, pyrilamine, and cimetidine did not. Endothelium removal abolished relaxation responses to ANG II and acetylcholine but not to isoproterenol or sodium nitroprusside. Inhibitors of phospholipase or arachidonic acid metabolism (quinacrine, indomethacin, 5,8,11,14-eicosatetraenoic acid, hydroquinone, metyrapone, SKF 525A) and a calcium channel blocker (verapamil) did not inhibit ANG II-induced relaxation, whereas indomethacin nearly completely blocked arachidonic acid-induced dilation of aortas with or without endothelia. Guanosine 3',5'-cyclic monophosphate (cGMP) levels in the aorta increased 15 s after ANG II application. Aortic relaxation was caused by 8-bromo-cGMP with or without intact endothelium. These results suggest that ANG II-induced relaxation of fowl aortas involves 1) an endothelium-dependent mechanism and 2) cGMP but not arachidonic acid metabolites.

Effects of kinins on isolated blood vessels. Role of endothelium

1982 ◽  
Vol 60 (12) ◽  
pp. 1580-1583 ◽  
Author(s):  
D. Regoli ◽  
J. Mizrahi ◽  
P. D'Orléans-Juste ◽  
S. Caranikas
Keyword(s):  
Arachidonic Acid ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Arachidonic Acid Metabolism ◽  
Arachidonic Acid Cascade ◽  
Vascular Smooth Muscles ◽  
Acid Metabolites

Bradykinin (BK) and des-Arg9-BK were used to determine whether the stimulatory and inhibitory actions of the kinins in various isolated vessels require the presence of endothelium and may be mediated by arachidonic acid metabolites. It was found that the presence of intact endothelium is required only for the relaxation of the dog common carotid artery in response to bradykinin. Stimulatory actions of both BK and des-Arg9-BK in arterial (rabbit aorta) and venous (rabbit jugular and mesenteric vein) smooth muscle do not require the presence of endothelium. Inhibition of the arachidonic acid cascade at various levels affects the relaxing action of acetylcholine (rabbit aorta and dog common carotid artery) while being inactive against both the relaxing (dog common carotid artery) and contractile actions (rabbit aorta, rabbit jugular and mesenteric veins) of bradykinin and des-Arg9-BK. Inhibitors of the arachidonic acid cascade also do not affect the inhibitory action of isopropylnoradrenaline on the rabbit aorta. The present results indicate that stimulant actions of kinins in isolated vascular smooth muscles do not require the presence of endothelium. Endothelium is required for the inhibitory actions of acetylcholine and bradykinin but not for that of isopropylnoradrenaline on the dog carotid artery. Moreover, the inhibition of arachidonic acid metabolism only affects the response of isolated vessels to acetylcholine. The present results suggest that several mechanisms may be involved in the inhibition of vascular tone by vasodilators.

scholarly journals Proteomic And Metabolomic Analyses Reveal The Full Spectrum of Inflammatory and Lipid Metabolic Abnormalities In Dyslipidemia

2020 ◽  
Author(s):  
Hui DU ◽  
Yifei RAO ◽  
Ronghua LIU ◽  
Kesui DENG ◽  
Yongmei GUAN ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Lipid Metabolism ◽  
Linoleic Acid ◽  
Metabolic Pathways ◽  
Inflammatory Responses ◽  
Arachidonic Acid Metabolism ◽  
Antioxidant Defenses ◽  
Alpha Linolenic Acid ◽  
Full Spectrum ◽  
Potential Biomarker

Abstract Background: Dyslipidemia is a common, chronic metabolic disease associated with cardiovascular complications. Due to the multiplicity of etiological factors, the pathogenesis of dyslipidemia is still unclear.Methods: In this study, we combined proteomics and metabolomics methods to analyze the plasma of patients with dyslipidemia and healthy subjects. ITRAQ markers, combined with LC-MS/MS proteomics technology and the UHPLC/ Orbitfast-X Tribrid system, were used to establish the metabolite profile in clinical dyslipidemia.Results: A total of 137 differentially expressed proteins were identified, mainly related to biological processes such as protein activation cascades, adaptive immune responses, complement activation, acute inflammatory responses and regulation of acute inflammatory responses. These proteins are involved in the regulation of important metabolic pathways, such as immunity and inflammation, coagulation and hemostasis, lipid metabolism, and oxidation and antioxidant defenses. Analysis of clinical metabolites showed there were 69 different metabolites in plasma, mainly related to glycerolipid, sphingolipid, porphyrin, alpha-linolenic acid, linoleic acid and arachidonic acid metabolism, suggesting that regulation of inflammation and lipid metabolism may be disturbed in patients with dyslipidemia. Among these, significant changes were observed in indole-3-propionic acid (IPA), which is considered a potential biomarker of dyslipidemia. Conclusions: Combined analysis of proteins and metabolites showed that arachidonic acid, linoleic acid and lipid metabolic pathways were closely related to dyslipidemia. IPA may be a potential biomarker.The information provided in this study may provide new insights into the pathogenesis of dyslipidemia and related diseases, as well as potential intervention targets.

scholarly journals Characterizing the Genomic Profile in High-Grade Gliomas: From Tumor Core to Peritumoral Brain Zone, Passing through Glioma-Derived Tumorspheres

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1157
Author(s):  
Martina Giambra ◽  
Eleonora Messuti ◽  
Andrea Di Cristofori ◽  
Clarissa Cavandoli ◽  
Raffaele Bruno ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Copy Number ◽  
Array Cgh ◽  
Bioinformatic Analysis ◽  
Genomic Profile ◽  
Copy Number Alterations ◽  
Disease Treatment ◽  
Genomic Knowledge ◽  
Two Samples ◽  
Canonical Pathways

Glioblastoma is an extremely heterogeneous disease. Treatment failure and tumor recurrence primarily reflect the presence in the tumor core (TC) of the glioma stem cells (GSCs), and secondly the contribution, still to be defined, of the peritumoral brain zone (PBZ). Using the array-CGH platform, we deepened the genomic knowledge about the different components of GBM and we identified new specific biomarkers useful for new therapies. We firstly investigated the genomic profile of 20 TCs of GBM; then, for 14 cases and 7 cases, respectively, we compared these genomic profiles with those of the related GSC cultures and PBZ biopsies. The analysis on 20 TCs confirmed the intertumoral heterogeneity and a high percentage of copy number alterations (CNAs) in GBM canonical pathways. Comparing the genomic profiles of 14 TC-GSC pairs, we evidenced a robust similarity among the two samples of each patient. The shared imbalanced genes are related to the development and progression of cancer and in metabolic pathways, as shown by bioinformatic analysis using DAVID. Finally, the comparison between 7 TC-PBZ pairs leads to identifying PBZ-unique alterations, which it has been identified, require further investigation.

scholarly journals Metabolomic profiling identifies novel associations with Electrolyte and Acid-Base Homeostatic patterns

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Cristina Menni ◽  
Linsay McCallum ◽  
Maik Pietzner ◽  
Jonas Zierer ◽  
Alisha Aman ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Metabolic Pathways ◽  
Enrichment Analysis ◽  
Serum Levels ◽  
Population Based ◽  
Pathway Enrichment Analysis ◽  
Serum Electrolyte ◽  
Independent Population ◽  
Pressure Lowering ◽  
Acid Metabolites

Abstract Electrolytes have a crucial role in maintaining health and their serum levels are homeostatically maintained within a narrow range by multiple pathways involving the kidneys. Here we use metabolomics profiling (592 fasting serum metabolites) to identify molecular markers and pathways associated with serum electrolyte levels in two independent population-based cohorts. We included 1523 adults from TwinsUK not on blood pressure-lowering therapy and without renal impairment to look for metabolites associated with chloride, sodium, potassium and bicarbonate by running linear mixed models adjusting for covariates and multiple comparisons. For each electrolyte, we further performed pathway enrichment analysis (PAGE algorithm). Results were replicated in an independent cohort. Chloride, potassium, bicarbonate and sodium associated with 10, 58, 36 and 17 metabolites respectively (each P < 2.1 × 10−5), mainly lipids. Of all the electrolytes, serum potassium showed the most significant associations with individual fatty acid metabolites and specific enrichment of fatty acid pathways. In contrast, serum sodium and bicarbonate showed associations predominantly with amino-acid related species. In the first study to examine systematically associations between serum electrolytes and small circulating molecules, we identified novel metabolites and metabolic pathways associated with serum electrolyte levels. The role of these metabolic pathways on electrolyte homeostasis merits further studies.

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