Flavonoids are functional constituents of many fruits and vegetables. Some flavonoids have antidiabetic properties because they improve altered glucose and oxidative metabolisms of diabetic states. Procyanidins are flavonoids with an oligomeric structure, and it has been shown that they can improve the pathological oxidative state of a diabetic situation. To evaluate their effects on glucose metabolism, we administered an extract of grape seed procyanidins (PE) orally to streptozotocin-induced diabetic rats. This had an antihyperglycemic effect, which was significantly increased if PE administration was accompanied by a low insulin dose. The antihyperglycemic effect of PE may be partially due to the insulinomimetic activity of procyanidins on insulin-sensitive cell lines. PE stimulated glucose uptake in L6E9 myotubes and 3T3-L1 adipocytes in a dose-dependent manner. Like insulin action, the effect of PE on glucose uptake was sensitive to wortmannin, an inhibitor of phosphoinositol 3-kinase and to SB203580, an inhibitor of p38 MAPK. PE action also stimulated glucose transporter-4 translocation to the plasma membrane. In summary, procyanidins have insulin-like effects in insulin-sensitive cells that could help to explain their antihyperglycemic effect in vivo. These effects must be added to their antioxidant activity to explain why they can improve diabetic situations.

Diet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases. Flavonoids appear to be promising candidates among the natural preventive treatments that have been identified to date. They have been shown to protect against several diseases, including CVD and various cancers. Furthermore, they have clear anti-inflammatory properties, which have primarily been evaluated in non-intestinal models. At present, a growing body of evidence suggests that flavonoids could exert a protective role against obesity-associated pathologies by modulating inflammatory-related cellular events in the intestine and/or the composition of the microbiota populations. The present paper will review the literature to date that has described the protective effects of flavonoids on intestinal inflammation, barrier integrity and gut microbiota in studies conducted using in vivo and in vitro models.

OBJECTIVE To investigate possible differences in Th1 and Th2 cytokine mRNA expression in the synovial tissue (ST) of patients with rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA) with diagnostic and/or pathogenic interest. METHODS Eleven RA patients and 14 SpA patients (10 with undifferentiated spondyloarthropathy (USpA), two with ankylosing spondylitis (AS) and two with psoriatic arthritis (PsA)) were included. Th1 (interferon γ, interleukin 2) and Th2 (interleukin 4, interleukin 5 and interleukin 10) cytokine mRNA levels from arthritic knee ST were quantified by using an optimised polymerase chain reaction method with a computerised analysis system. Protein levels of proinflammatory cytokines (interleukin 1, tumour necrosis factor α and interleukin 6) in synovial fluid were quantified with a specific ELISA test. RESULTS Th1 cytokines were detected in all of RA ST samples in contrast with 58% (interferon γ) and 71% (interleukin 2) of SpA samples. Th2 cytokines were expressed in 90% of RA ST samples, but the findings in SpA were interleukin 10 in 90%, interleukin 4 in 60% and interleukin 5 in 40% of ST samples. However, when the mRNA levels of each cytokine were quantified and corrected for T cell mRNA levels, only interferon γ levels were significantly higher in RA than in SpA (p<0.003). Thus, the Th1/Th2 cytokine ratio in RA was fivefold that of SpA. Synovial fluid interleukin 1β concentrations were higher in RA than in SpA (p<0.05); there were also higher synovial fluid levels of tumour necrosis factor α in RA than in SpA, but without statistical significance. CONCLUSION This study has detected both Th1 and Th2 cytokine gene expression in ST from RA and SpA patients. Synovium interferon γ mRNA levels and SF interleukin 1β protein levels were significantly higher in RA than in SpA, so reflecting the known proinflammatory activity of interferon γ through macrophage activation. Thus, the Th1 (interferon γ)/Th2 (interleukin 4) ratio is significantly higher in RA than in SpA ST. These data confirm previous studies on ST Th1/Th2 balance in RA and extend previous work in comparing ST RA with subgroups of SpA distinct of ReA.