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We studied the anti-arthritic activity of glucomannan (GM) isolated from Candida utilis and of Imunoglukán®, a beta-(1,3/1,6)-D-glucan (IMG) isolated from Pleurotus ostreatus. Adjuvant arthritis (AA) was induced intradermally by the injection of Mycobacterium butyricum in incomplete Freund's adjuvant to Lewis rats. Blood for biochemical and immunological analysis was collected on experimental days 1, 14, 21, and 28. A clinical parameter - hind paw volume (HPV) - was also measured. The detection of IL-1 alpha, IL-4, TNF alpha, and MCP-1 was done by immunoflowcytometry. On day 28 - the end of the experiment - we determined spectrophotometrically: the total anti-oxidant status (TAS) of plasma samples along with thiobarbituric acid-reacting substances (TBARS) levels in plasma and we assessed the activity of gamma-glutamyl transferase (GGT) in hind paw joint homogenate. The experiments included healthy animals, arthritic animals without treatment, and arthritic animals with administration of glucomannan (GM-AA) in the oral daily dose of 15 mg/kg b.w. and of IMG (IMG-AA) in the oral daily dose of 2 mg/kg b.w. The progress of AA was manifested by all parameters monitored. Both substances had beneficial effects on HPV, TBARS levels, GGT activity, and TAS levels. For cytokine assessment, only IMG-AA samples were selected, considering the significant HPV improvement accompanied with the observed anti-oxidant action. IMG administration had a positive immunomodulating effect on all cytokine plasma levels measured, changed markedly due to arthritis progression. Thus, IMG may be considered as a candidate for combinatorial therapy of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background & Aims: There is convincing clinical evidence to suggest that flavanol-containing foods/beverages are capable of inducing improvements in human vascular function. However, whilst (-)-epicatechin has been tested for efficacy, a full dose-dependency has yet to be established, particularly at doses below 1 mg/kg BW. The current study examined the dose-dependent effects of (-)-epicatechin on human vascular function with concurrent measurement of plasma (-)-epicatechin metabolites and levels of circulating nitrite and nitrate species, NO x ., Methods: An acute, double-blind, placebo-controlled, crossover intervention trial was conducted in 20 healthy males with 4 treatment arms: water-based (-)-epicatechin (0.1, 0.5 and 1.0 mg/kg BW) and a water only as control. Vascular function was assessed by flow-mediated dilatation (FMD) measured at the brachial artery, laser Doppler imaging with iontophoresis (LDI) at the subcutaneous capillaries of the forearm (response to Ach and SNP) and peripheral blood pressure (BP) at baseline, 1, 2, 4 and 6 h post-intervention. Plasma analysis of epicatechin metabolites was conducted by LC-MS and circulating plasma of nitrite and nitrate species were performed using an HPLC-based system (ENO-30)., Results: Significant increases in % FMD were found to occur at 1 and 2 h following intake of 1 mg/kg BW, and at 2 h for the 0.5 mg/kg BW intake. There were no significant changes in LDI or BP at any time-points or intake levels. Increases in FMD over the 6 h timeframe were closely paralleled by the appearance of total plasma (-)-epicatechin metabolites. Non-significant changes in circulating NOx was observed., Conclusions: Our data add further evidence that (-)-epicatechin is a causal vasoactive molecule within flavanol-containing foods/beverages. In addition, we show for the first time that intake levels as low as 0.5 mg/kg BW are capable of inducing acute improvements in vascular function (FMD) in healthy volunteers., (Copyright © 2019. Published by Elsevier Ltd.)

Assessment of the flavanol composition of 41 commercial chocolates was by HPLC-DAD. Among individual flavonols ranged from 0.095 to 3.264mgg(-1), epicatechin was the predominant flavanol accounting for 32.9%. Contrary to catechin, epicatechin was a reliable predictive value of the polyphenol content. Conversely the percentage of theobromine used as a proxy measure for nonfat cocoa solids (NFCS) was not a good predictor of epicatechin or flavanol content. In a further chiral analysis, the naturally occurring forms of cocoa flavanols, (-)-epicatechin and (+)-catechin, was determined joint the occurrence of (+)-epicatechin and (-)-catechin due to the epimerization reactions produced in chocolate manufacture. (-)-Epicatechin, the most bioactive compound and predominant form accounted of 93%. However, no positive correlation was found with% cocoa solids, the most significant quality parameter., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

There is increasing evidence to suggest that neuroinflammatory processes contribute to the cascade of events that lead to the progressive neuronal damage observed in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Therefore, treatment regimes aimed at modulating neuroinflammatory processes may act to slow the progression of these debilitating brain disorders. Recently, a group of dietary polyphenols known as flavonoids have been shown to exert neuroprotective effects in vivo and in neuronal cell models. In this review we discuss the evidence relating to the modulation of neuroinflammation by flavonoids. We highlight the evidence which suggests their mechanism of action involves: 1) attenuation of the release of cytokines, such as interleukin-1beta (IL-1beta and tumor necrosis factor-alpha (TNF-alpha); 2) an inhibitory action against inducible nitric oxide synthase (iNOS) induction and subsequent nitric oxide (NO(*)) production; 3) inhibition of the activation of NADPH oxidase and subsequent reactive oxygen species generation; 4) a capacity to down-regulate the activity of pro-inflammatory transcription factors such as nuclear factor-kappaB (NF-kappaB); and 5) the potential to modulate signalling pathways such as mitogen-activated protein kinase (MAPK) cascade. We also consider the potential of these dietary compounds to represent novel therapeutic agents by considering their metabolism in the body and their ability to access the brain via the blood brain barrier. Finally, we discuss future areas of study which are necessary before dietary flavonoids can be established as therapeutic agents against neuroinflammation.

The aim of this study was to investigate the potential of quercetin and two of its "in vivo" metabolites, 3'-O-methyl quercetin and 4'-O-methyl quercetin, to protect H9c2 cardiomyoblasts against H(2)O(2)-induced oxidative stress. As limited data are available regarding the potential uptake and cellular effects of quercetin and its metabolites in cardiac cells, we have evaluated the cellular association/uptake of the three compounds and their involvement in the modulation of two pro-survival signalling pathways: ERK1/2 signalling cascade and PI3K/Akt pathway. The three flavonols associated with cells to differing extents. Quercetin and its two O-methylated metabolites were able to reduce intracellular ROS production but only quercetin was able to counteract H(2)O(2) cell damage, as measured by MTT reduction assay, caspase-3 activity and DNA fragmentation assays. Furthermore, only quercetin was observed to modulate pro-survival signalling through ERK1/2 and PI3K/Akt pathway. In conclusion we have demonstrated that quercetin, but not its O-methylated metabolites, exerts protective effects against H(2)O(2) cardiotoxicity and that the mechanism of its action involves the modulation of PI3K/Akt and ERK1/2 signalling pathways.

Objective: Peroxynitrite (ONOO(-)) is formed in the inflamed and degenerating human joint. Peroxynitrite-modified collagen-II (PMC-II) was recently discovered in the serum of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Therefore we investigated the cellular effects of PMC-II on human mesenchymal progenitor cells (MPCs) as a model of cartilage and cartilage repair cells in the inflamed and degenerating joint., Design: MPCs were isolated from the trabecular bone of patients undergoing reconstructive surgery and were differentiated into a chondrogenic lineage. Cells were exposed to PMC-II and levels of the proinflammatory mediators nitric oxide (*NO) and prostaglandin E(2) (PGE(2)) measured. Levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), phosphorylated mitogen activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kappaB) activation were measured by enzyme linked immunosorbent assay (ELISA) together with specific MAPK and NF-kappaB inhibitors., Results: PMC-II induced ()NO and PGE(2) synthesis through upregulation of iNOS and COX-2 proteins. PMC-II also lead to the phosphorylation of MAPKs, extracellularly regulated kinase 1/2 (ERK1/2) and p38 [but not c-Jun NH(2)-terminal kinase (JNK1/2)] and the activation of proinflammatory transcription factor NF-kappaB. Inhibitors of p38, ERK1/2 and NF-kappaB prevented PMC-II induced ()NO and PGE(2) synthesis, iNOS and COX-2 protein expression and NF-kappaB activation., Conclusion: iNOS, COX-2, NF-kappaB and MAPK are known to be activated in the joints of patients with OA and RA. PMC-II induced iNOS and COX-2 synthesis through p38, ERK1/2 and NF-kappaB dependent pathways suggesting a previously unidentified pathway for the synthesis of the proinflammatory mediators, ()NO and PGE(2), further suggesting that inhibitors of these pathways may be therapeutic in the inflamed and degenerating human joint.