Green tea extract decreases oxidative stress and improves insulin sensitivity in an animal model of insulin resistance, the fructose-fed rat.

BACKGROUND: Tea polyphenols, as both insulin potentiating factors and antioxidants, are postulated to act in preventing the metabolic syndrome, which is characterized by insulin resistance, dyslipidemia, and increased oxidative stress. OBJECTIVE AND METHODS: Using an animal model of insulin resistance, our objective was to determine the effects of a green tea extract on oxidative stress parameters and insulin sensitivity. Wistar rats, 10 per group, received a high-fructose diet (FD) for 6 weeks, or the same diet (FD) plus 1 or 2 g of green tea solids/kg diet. RESULTS: Signs of insulin resistance (hyperglycemia, hypertriglyceridemia, and hyperinsulinemia) developed in rats receiving the FD, but not in those of the control group. In contrast, animals receiving added tea solids exhibited decreases in glycemia, insulinemia, and triglyceridemia, consistent with an insulin-potentiating effect of tea. In parallel, oxidative stress was decreased by tea consumption with lower plasma lipid peroxidation, sulfhydryl (SH) group oxidation, and DNA oxidative damage. In summary, the addition of green tea extracts to the diet, inducing insulin resistance, led to protective effects of green tea against both oxidative stress and insulin resistance. CONCLUSIONS: These data suggest that green tea may be beneficial for people with decreased insulin sensitivity and increased oxidative stress, such as those with the metabolic syndrome or type 2 diabetes.

Green tea polyphenol extract regulates the expression of genes involved in glucose uptake and insulin signaling in rats fed a high fructose diet.

Green tea has antidiabetic, antiobesity, and anti-inflammatory activities in animal models, but the molecular mechanisms of these effects have not been fully understood. Quantitative real-time polymerase chain reaction (PCR) was used to investigate the relative expression levels and the effects of green tea (1 and 2 g solid extract/kg diet) on the expression of glucose transporter family genes (Glut1/Slc2a1, Glut2/Slc2a2, Glut3/Slc2a3, and Glut4/Slc2a4) and insulin signaling pathway genes (Ins1, Ins2, Insr, Irs1, Irs2, Akt1, Grb2, Igf1, Igf2, Igf1r, Igf2r, Gsk3b, Gys1, Pik3cb, Pik3r1, Shc1, and Sos1) in liver and muscle of rats fed a high-fructose diet known to induce insulin resistance and oxidative stress. Glut2 and Glut4 were the major Glut mRNAs in rat liver and muscle, respectively. Green tea extract (1 g) increased Glut1, Glut4, Gsk3b, and Irs2 mRNA levels by 110, 160, 30, and 60% in the liver, respectively, and increased Irs1 by 80% in the muscle. Green tea extract (2 g) increased Glut4, Gsk3b, and Pik3cb mRNA levels by 90, 30, and 30% but decreased Shc1 by 60% in the liver and increased Glut2, Glut4, Shc1, and Sos1 by 80, 40, 60, and 50% in the muscle. This study shows that green tea extract at 1 or 2 g/kg diet regulates gene expression in the glucose uptake and insulin signaling pathway in rats fed a fructose-rich diet.

Green tea increases anti-inflammatory tristetraprolin and decreases pro-inflammatory tumor necrosis factor mRNA levels in rats.

BACKGROUND: Tristetraprolin (TTP/ZFP36) family proteins have anti-inflammatory activity by binding to and destabilizing pro-inflammatory mRNAs such as Tnf mRNA, and represent a potential therapeutic target for inflammation-related diseases. Tea has anti-inflammatory properties but the molecular mechanisms have not been completely elucidated. We hypothesized that TTP and/or its homologues might contribute to the beneficial effects of tea as an anti-inflammatory product. METHODS: Quantitative real-time PCR was used to investigate the effects of green tea (0, 1, and 2 g solid extract/kg diet) on the expression of Ttp family genes (Ttp/Tis11/Zfp36, Zfp36l1/Tis11b, Zfp36l2/Tis11d, Zfp36l3), pro-inflammatory genes (Tnf, Csf2/Gm-csf, Ptgs2/Cox2), and Elavl1/Hua/Hur and Vegf genes in liver and muscle of rats fed a high-fructose diet known to induce insulin resistance, oxidative stress, inflammation, and TNF-alpha levels. RESULTS: Ttp and Zfp36l1 mRNAs were the major forms in both liver and skeletal muscle. Ttp, Zfp36l1, and Zfp36l2 mRNA levels were more abundant in the liver than those in the muscle. Csf2/Gm-csf and Zfp36l3 mRNAs were undetectable in both tissues. Tea (1 g solid extract/kg diet) increased Ttp mRNA levels by 50-140% but Tnf mRNA levels decreased by 30% in both tissues, and Ptgs2/Cox2 mRNA levels decreased by 40% in the muscle. Tea (2 g solid extract/kg diet) increased Elavl1/Hua/Hur mRNA levels by 40% in the liver but did not affect any of the other mRNA levels in liver or muscle. CONCLUSION: These results show that tea can modulate Ttp mRNA levels in animals and suggest that a post-transcriptional mechanism through TTP could partially account for tea's anti-inflammatory properties. The results also suggest that drinking adequate amounts of green tea may play a role in the prevention of inflammation-related diseases.

Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage inflammatory mediators.

Pentahydroxyflavone dihydrate, quercetin (QU) is one of common flavonols biosynthesized by plants and has been suggested to modulate inflammatory responses in various models. In the present study, we investigated in vivo effects of oral or intra-cutaneous QU in chronic rat adjuvant-induced arthritis (AA). Growth delay and arthritic scores were evaluated daily after AA induction in Lewis rats. Oral administration of QU (5 x 160 mg/kg) to arthritic rats resulted in a clear decrease of clinical signs compared to untreated controls. Intra-cutaneous injections of lower doses (5 x 60 mg/kg) of QU gave similar anti-arthritic effects, while 5 x 30 mg/kg concentrations were inefficient in this respect. Finally, injection of relatively low QU doses (5 x 30 mg/kg) prior to AA induction significantly reduced arthritis signs. As QU was suggested to inhibit macrophage-derived cytokines and nitric oxide (NO), we then analyzed macrophage response ex vivo. Anti-arthritic effects of QU correlated with significant decrease of inflammatory mediators produced by peritoneal macrophages, ex vivo and in vitro. These data indicate that QU is a potential anti-inflammatory therapeutic and preventive agent targeting the inflammatory response of macrophages.

Quercetin induces apoptosis of Trypanosoma brucei gambiense and decreases the proinflammatory response of human macrophages.

In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)-alpha and nitric oxide derivatives. In the present study, quercetin (3,3',4',5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-alpha and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis.