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1.
Clin Nutr ; 40(2): 445-459, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33041091

RESUMO

BACKGROUND & AIMS: Omega-3 polyunsaturated fatty acid (ω-3 PUFA) have been reported to have beneficial cardiovascular effects, but its mechanism of protection against acute myocardial infarction (AMI) who are under guideline-based therapy is not fully understood. Here, we used a metabolomic approach to systematically analyze the eicosanoid metabolites induced by ω-3 PUFA supplementation and investigated the underlying mechanisms. METHODS: Participants with AMI after successful percutaneous coronary intervention were randomized to 3 months of 2 g daily ω-3 PUFA and guideline-adjusted therapy (n = 30, ω-3 therapy) or guideline-adjusted therapy alone (n = 30, Usual therapy). Functional PUFA-derived eicosanoids in plasma were profiled by metabolomics. Clinical and laboratory tests were obtained before and 3 months after baseline and after the study therapy. RESULTS: By intent-to-treat analysis, the content of 11-HDoHE, 20-HDoHE and 16,17-EDP and that of epoxyeicosatetraenoic acids (EEQs), derived from docosahexaenoic acid and eicosapentaenoic acid, respectively, were significantly higher with ω-3 group than Usual therapy, whereas that of prostaglandin J2 (PGJ2) and leukotriene B4, derived from arachidonic acid, was significantly decreased. As compared with Usual therapy, ω-3 PUFA therapy significantly reduced levels of triglycerides (-6.3%, P < 0.05), apolipoprotein B (-4.9%, P < 0.05) and lipoprotein(a) (-37.0%, P < 0.05) and increased nitric oxide level (62.2%, P < 0.05). In addition, the levels of these variables were positively correlated with change in 16,17-EDP and EEQs content but negatively with change in PGJ2 content. CONCLUSIONS: ω-3 PUFA supplementation may improve lipid metabolism and endothelial function possibly by affecting eicosanoid metabolic status at a systemic level during convalescent healing after AMI. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn. Unique identifier: ChiCTR1900025859.


Assuntos
Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Ácidos Graxos Ômega-3/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Infarto do Miocárdio/terapia , Doença Aguda , Idoso , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Morte Súbita Cardíaca/prevenção & controle , Eicosanoides/sangue , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Análise de Intenção de Tratamento , Leucotrieno B4/sangue , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Óxido Nítrico/biossíntese , Política Nutricional , Intervenção Coronária Percutânea , Prostaglandina D2/análogos & derivados , Prostaglandina D2/sangue
2.
Clin Exp Pharmacol Physiol ; 47(7): 1134-1144, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32068900

RESUMO

Glycerophospholipids (GPs) and sphingolipids (SPs) are important lipid components in the body and play biological functions. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are important nutrients, and their supplements are commonly used for preventing some diseases. However, the effect of n-3 PUFAs on the human glycerophospholipidome and sphingolipidome is unclear. We used targeted lipidomics to study the GP and SP profile of healthy individuals after supplementation with n-3 PUFAs for 3, 7, 14 and 21 days. Fuzzy c-means clustering was used to cluster the lipid species into six classes reflecting different changed-content patterns after n-3 PUFA supplementation. Among the species with significantly changed content, lysophospholipids were the most sensitive; their content started to increase on day 3. The content of phosphatidylserines increased at a later stage. The content of most of the phosphatidylcholines and alkylphosphatidylcholines decreased on day 21. A correlation network analysis of lipid species suggested that some enzymes involved in the metabolism of lysophospholipids and phosphatidylserines were regulated by n-3 PUFAs. Levels of creatine kinase-MB (CK-MB), urea, glucose, triglycerides and total bilirubin were altered by n-3 PUFA at 21 days. Correlation analysis revealed that the level of CK-MB was negatively correlated with those of species in lysophosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine and phosphatidylserine classes, which were increased by n-3 PUFA supplementation. With the analysis in this work, we demonstrated the regular pattern of n-3 PUFAs on GP and SP metabolism, which provides a pharmacological basis for n-3 PUFAs for clinical application.


Assuntos
Suplementos Nutricionais/análise , Ácidos Graxos Ômega-3/farmacologia , Lipidômica , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino
3.
Clin Exp Pharmacol Physiol ; 46(8): 705-710, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30983029

RESUMO

Pre-eclampsia (PE) is considered a leading cause of mortality and morbidity in pregnant women worldwide. Eicosanoids derived from polyunsaturated fatty acids (PUFAs) might play an important role in the occurrence and development of PE. Omega-3 PUFAs are nutrients that are popular supplements for pregnant women and can reduce blood pressure. However, the levels of eicosanoids derived from omega-3 PUFAs in women with PE is not clear. The purpose of this study was to investigate the eicosanoid metabolic signature of PE. We performed a case-control study using data for pregnant women (n = 10) with PE and normotensive pregnant women (n = 10). We investigated the difference in eicosanoid profile between the groups by LC-MS/MS-based metabolomics. The plasma levels of arachidonic acid metabolites and some of the lipoxygenase metabolites of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) showed an increasing trend, and those of the cytochrome P450 metabolites of EPA and DHA were decreased in women with PE. Levels of leukotriene B4, 14,15-dihydroxy-eicosatetraenoate, 16-hydroxydocosahexaenoic acid and 8,9-epoxy eicosatetraenoic acid were significantly correlated with PE occurrence. These eicosanoids might take part in the progression of PE in pregnant women.


Assuntos
Eicosanoides/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Metabolômica , Pré-Eclâmpsia/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Adulto Jovem
4.
Acta Pharmaceutica Sinica ; (12): 1451-1456, 2014.
Artigo em Chinês | WPRIM | ID: wpr-299112

RESUMO

To evaluate the differences of Ophiopogonjaponicus from different cultivations, the metabolomics based method was conducted to compare the effects of Hangmaidong and Chuanmaidong (Chinese name) on plasma endogenous metabolites of normal rats. Data were collected by ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS), and were analyzed by multivariate statistical method, such as Principal Component Analysis and Orthogonal Signal Correction Partial Least Square Discriminant Analysis. Results revealed that the plasma metabolites profiling of low and middle dose group of Chuanmaidong were similar to the control group, but different from the high dose group obviously. Meanwhile the high, middle and low dose groups of Hangmaidong were different from control group notably, and the difference is dose dependent. Lysophosphatidylcholines, the possible endogenous metabolites which contribute to the classification most significantly, are closely related to cardiovascular system diseases. Compared with the group of Chuanmaidong, Hangmaidong has greater impact on the plasma metabolic profiling of normal rats. Hangmaidong and Chuanmaidong showed significant differences pharmacodynamically.


Assuntos
Animais , Ratos , Biomarcadores , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Farmacologia , Análise dos Mínimos Quadrados , Espectrometria de Massas , Metabolômica , Análise de Componente Principal
5.
Artigo em Chinês | WPRIM | ID: wpr-324343

RESUMO

<p><b>OBJECTIVE</b>To establish a RP-HPLC method for the determination of swertiamarin, sweroside, gentiopicrin and oleanolic acid in different parts of Swertia pseudochinesis.</p><p><b>METHOD</b>A Zorbax SB-C18 (4.6 mm x 250 mm, 5 microm) column was used with acetonitrile-water (10:90) and methnol-water(86:14) at detection wavelengths of 238 nm, 246 nm, 274 nm and 207 nm for swertiamarin, sweroside, gentiopicrin and oleanolic acid respectively. The flow rate was 1.0 mL x min(-1) and the column temperature was 25 degrees C.</p><p><b>RESULT</b>All of the compounds were based--isolated. The linear ranges of swertiamarin, sweroside, gentiopicrin and oleanolic acid were 0.068 9-0.344 4(r = 0.999 2) , 0.001 1-0.014 0 (r2 = 0. 999 8), 0.001 1-0.013 4 (r2 = 0.999 9) and 0.001 1-0.008 8 mg x mL(-1) (r2 = 0. 999 6), respectively.</p><p><b>CONCLUSION</b>The method is simple and accurate, which can be used for quality control of S. pseudochinesis.</p>


Assuntos
Cromatografia Líquida de Alta Pressão , Métodos , Flores , Química , Glucosídeos , Glucosídeos Iridoides , Iridoides , Ácido Oleanólico , Folhas de Planta , Química , Raízes de Plantas , Química , Caules de Planta , Química , Plantas Medicinais , Química , Pironas , Reprodutibilidade dos Testes , Swertia , Química , Triterpenos
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