Impact of Polyphenols on Inflammatory and Oxidative Stress Factors in Diabetes Mellitus: Nutritional Antioxidants and Their Application in Improving Antidiabetic Therapy.

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia and oxidative stress. Oxidative stress plays a crucial role in the development and progression of diabetes and its complications. Nutritional antioxidants derived from dietary sources have gained significant attention due to their potential to improve antidiabetic therapy. This review will delve into the world of polyphenols, investigating their origins in plants, metabolism in the human body, and relevance to the antioxidant mechanism in the context of improving antidiabetic therapy by attenuating oxidative stress, improving insulin sensitivity, and preserving ß-cell function. The potential mechanisms of, clinical evidence for, and future perspectives on nutritional antioxidants as adjuvant therapy in diabetes management are discussed.

Evidence from a Systematic Review and Meta-Analysis Pointing to the Antidiabetic Effect of Polyphenol-Rich Plant Extracts from Gymnema montanum, Momordica charantia and Moringa oleifera.

In vitro and animal model studies are of great interest for selecting new phytochemicals, including polyphenols with antioxidative properties, as candidates for antidiabetic drugs. This review provides evidence from a critical literature data analysis on the effects of plant extract supplementation in diabetes mellitus management. We considered and meta-analyzed the efficacy of oral supplementation of plant extracts in animal model studies and examined physiological and oxidative stress parameters. Finally, 23 articles were included in the meta-analysis, revealing three plants with experimentally confirmed in vivo and in vitro antidiabetic properties: Gymnema montanum, Momordica charantia and Moringa oleifera. The following parameter changes resulted from an investigation of the supplementation: reduced oxidative stress, decreased insulin resistance, increased insulin release, reduced adiposity, and a modulatory effect on glycolysis and gluconeogenesis, as well as attenuation of diabetes-associated weight loss, reduced fasting blood glucose and lowered oxidative status. A comparison of Gymnema montanum versus Glybenclamide revealed the superiority of extracts over drug administration in some aspects. Although the analyzed extracts are promising candidates for antidiabetic treatment, there is much inconsistent data in the literature. Therefore, ultimate references for using these compounds in the prevention of diabetes are currently not applicable.

Plasma Amino Acids May Improve Prediction Accuracy of Cerebral Vasospasm after Aneurysmal Subarachnoid Haemorrhage.

Aneurysmal subarachnoid haemorrhages (aSAH) account for 5% of strokes and continues to place a great burden on patients and their families. Cerebral vasospasm (CVS) is one of the main causes of death after aSAH, and is usually diagnosed between day 3 and 14 after bleeding. Its pathogenesis remains poorly understood. To verify whether plasma concentration of amino acids have prognostic value in predicting CVS, we analysed data from 35 patients after aSAH (median age 55 years, IQR 39-62; 20 females, 57.1%), and 37 healthy volunteers (median age 50 years, IQR 38-56; 19 females, 51.4%). Fasting peripheral blood samples were collected on postoperative day one and seven. High performance liquid chromatography-mass spectrometry (HPLC-MS) analysis was performed. The results showed that plasma from patients after aSAH featured a distinctive amino acids concentration which was presented in both principal component analysis and direct comparison. No significant differences were noted between postoperative day one and seven. A total of 18 patients from the study group (51.4%) developed CVS. Hydroxyproline (AUC = 0.7042, 95%CI 0.5259-0.8826, p = 0.0248) and phenylalanine (AUC = 0.6944, 95%CI 0.5119-0.877, p = 0.0368) presented significant CVS prediction potential. Combining the Hunt-Hess Scale and plasma levels of hydroxyproline and phenylalanine provided the model with the best predictive performance and the lowest leave-one-out cross-validation of performance error. Our results suggest that plasma amino acids may improve sensitivity and specificity of Hunt-Hess scale in predicting CVS.

Targeted and untargeted metabolomic approach for GDM diagnosis.

Gestational diabetes mellitus (GDM) is a disorder which manifests itself for the first time during pregnancy and is mainly connected with glucose metabolism. It is also known that fatty acid profile changes in erythrocyte membranes and plasma could be associated with obesity and insulin resistance. These factors can lead to the development of diabetes. In the reported study, we applied the untargeted analysis of plasma in GDM against standard glucose-tolerant (NGT) women to identify the differences in metabolomic profiles between those groups. We found higher levels of 2-hydroxybutyric and 3-hydroxybutyric acids. Both secondary metabolites are associated with impaired glucose metabolism. However, they are products of different metabolic pathways. Additionally, we applied lipidomic profiling using gas chromatography to examine the fatty acid composition of cholesteryl esters in the plasma of GDM patients. Among the 14 measured fatty acids characterizing the representative plasma lipidomic cluster, myristic, oleic, arachidonic, and α-linoleic acids revealed statistically significant changes. Concentrations of both myristic acid, one of the saturated fatty acids (SFAs), and oleic acid, which belong to monounsaturated fatty acids (MUFAs), tend to decrease in GDM patients. In the case of polyunsaturated fatty acids (PUFAs), some of them tend to increase (e.g., arachidonic), and some of them tend to decrease (e.g., α-linolenic). Based on our results, we postulate the importance of hydroxybutyric acid derivatives, cholesteryl ester composition, and the oleic acid diminution in the pathophysiology of GDM. There are some evidence suggests that the oleic acid can have the protective role in diabetes onset. However, metabolic alterations that lead to the onset of GDM are complex; therefore, further studies are needed to confirm our observations.

Polyphenol Extract from Evening Primrose (Oenothera paradoxa) Inhibits Invasion Properties of Human Malignant Pleural Mesothelioma Cells.

Extracts from the defatted evening primrose (Oenothera paradoxa Hudziok) seeds are the source of a range of stable polyphenolic compounds, including ellagic acid, gallic acid, and catechin. Our studies evaluate, for the first time, the influence of evening primrose isopropanol extract (EPE) on malignant pleural mesothelioma (MPM) cells. MPM is rarely diagnosed, its high aggressiveness and frequently noted chemoresistance limit its treatment schemes and it is characterized by low prognostic features. Here, we demonstrate that EPE inhibited MPM growth in a dose-dependent manner in cells with increased invasion properties. Moreover, EPE treatment resulted in cell cycle arrest in the G2/M phase and increased apoptosis in invasive MPM cell lines. Additionally, EPE strongly limited invasion and MMP-7 secretion in MPM cancer cells. Our original data provide evidence about the potential anti-invasive effects of EPE in MPM therapy treatment.

Associations of Arginine with Gestational Diabetes Mellitus in a Follow-Up Study.

In the reported study we applied the targeted metabolomic profiling employing high pressure liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-MS/MS) to understand the pathophysiology of gestational diabetes mellitus (GDM), early identification of women who are at risk of developing GDM, and the differences in recovery postpartum between these women and normoglycemic women. We profiled the peripheral blood from patients during the second trimester of pregnancy and three months, and one year postpartum. In the GDM group Arg, Gln, His, Met, Phe and Ser were downregulated with statistical significance in comparison to normoglycemic (NGT) women. From the analysis of the association of all amino acid profiles of GDM and NGT women, several statistical models predicting diabetic status were formulated and compared with the literature, with the arginine-based model as the most promising of the screened ones (area under the curve (AUC) = 0.749). Our research results have shed light on the critical role of arginine in the development of GDM and may help in precisely distinguishing between GDM and NGT and earlier detection of GDM but also in predicting women with the increased type 2 diabetes mellitus (T2DM) risk.

Analytical techniques for multiplex analysis of protein biomarkers.

INTRODUCTION: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research. AREAS COVERED: We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses. EXPERT COMMENTARY: The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine.

Lipid profile changes in erythrocyte membranes of women with diagnosed GDM.

Gestational diabetes mellitus (GDM) is a glucose intolerance that begins or is first recognized during pregnancy. It is currently a growing health problem worldwide affecting from 1% to 14% of all pregnant women depending on racial and ethnic group as well as the diagnostic and screening criteria. Our preliminary study aimed at investigating the erythrocyte membrane fatty acid profiles of pregnant women, in particular with diagnosed with gestational diabetes mellitus (GDM), and with normal glucose tolerant (NGT) pregnant women as a control group. The study group comprised 43 pregnant women, 32 of whom were diagnosed with GDM according to the WHO criteria, and 11 with normal glucose tolerance. The erythrocyte membrane phospholipids were obtained according to the Folch extraction procedure. Fatty acids (FA) were analyzed by gas chromatography (GC) as the corresponding fatty acid methyl esters (FAME). A cluster of 14 fatty acids identified contained >98% of the recognized peaks in the GC analysis. The analysis of fatty acids from erythrocytes revealed important differences between GDM and NGT women in the third trimester, and the results were correlated with biochemical data. Among the 14 measured FA representing the membrane lipidomic profile, the levels of three saturated FA (myristic, palmitic, stearic acids) tended to decrease in GDM patients, with the percentage content of stearic acid significantly changed. The relative content of monounsaturated fatty acids (MUFA) tended to increase, in particular the oleic acid and vaccenic acid contents were significantly increased in erythrocyte membranes of the GDM group in comparison with the NGT group. The GDM group demonstrated higher sapienic acid levels (+29%) but this change was not statistically significant. This study revealed association between an impaired cis-vaccenic acid concentration in erythrocytes membrane and GDM development. No significant changes of polyunsaturated fatty acids (PUFA) were observed in GDM and NGT erythrocytes. We postulate, basing on the differences between the GDM and NGT lipidomic profiles, that stearic and cis-vaccenic acids can be considered as dual biomarkers of specific SFA-MUFA conversion pathway, involving the coupling of delta-9 desaturase and elongase enzymes. Our results indicate that the SFA-MUFA families may be involved in the pathophysiology of metabolic diseases such as GDM, but the further studies are needed to confirm our hypothesis. In conclusion, the erythrocyte membranes of GDM women undergo remodeling resulting in abnormal fatty acid profiles, which are reflection of the long-term status of organism and can have great impact on both the mother and her offspring.

Dual stimulus-dependent effect of Oenothera paradoxa extract on the respiratory burst in human leukocytes: suppressing for Escherichia coli and phorbol myristate acetate and stimulating for formyl-methionyl-leucyl-phenylalanine.

Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA), and formyl-methionyl-leucyl-phenylalanine (fMLP). Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05) and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05). Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-ß-(D)-glucose (PGG), the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC) coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans.