With the dramatically increasing prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide, there is an urgent need for new strategies to combat the growing epidemic of these metabolic ...diseases. Diet is an essential factor affecting the development of and risk for obesity and T2DM and it can either help or hurt. In searching for preventative and therapeutic strategies, it is therefore advantageous to consider the potential of certain foods and their bioactive compounds to reverse or prevent the pathogenic processes associated with metabolic disease. Anthocyanins are naturally occurring polyphenolic compounds abundant in dark-colored fruits, vegetables and grains. Epidemiological studies suggest that increased consumption of anthocyanins lowers the risk of T2DM. Many
in vitro
and
in vivo
studies also reveal an array of mechanisms through which anthocyanins could prevent or reverse obesity- and T2DM-related pathologies including promotion of antioxidant and anti-inflammatory activities, improvement of insulin resistance, and hypolipidemic and hypoglycemic actions. Here, we summarize the data on anthocyanin-mediated protection against obesity and T2DM and the underlying mechanisms. Further population-based and long-term human intervention studies are necessary to ultimately evaluate the use of anthocyanins for protection/prevention against the development of obesity and T2DM.
Scope
Quercetin is a typical flavonol with atheroprotective effects, but the effect of quercetin on dendritic cell (DC) maturation in relation to atherosclerosis has not yet been clearly defined. ...Thus, we investigated whether quercetin can inhibit DC maturation and evaluated its potential value in atherosclerosis progression in ApoE−/− mice.
Methods and results
Quercetin consumption inhibited DC activation, inflammatory response and suppressed the progression of atherosclerosis in ApoE−/− mice. Subsequently, quercetin treatment inhibited the phenotypic and functional maturation of DCs, as evidenced not only by downregulation of CD80, CD86, MHC‐II, IL‐6 and IL‐12 but also by a reduction in the ability to stimulate T cell allogeneic proliferation. Finally, an in vitro study demonstrated that quercetin inhibited DC maturation via upregulation of Dabs, which then downregulated the Src/PI3K/Akt‐NF‐κB‐inflammatory pathways.
Conclusions
Our data indicate that quercetin attenuates atherosclerosis progression by regulating DC activation via Dab2 protein expression.
Quercetin effectively attenuates atherosclerosis progression by suppressing dendritic cell (DC) activation. The molecular mechanism by which quercetin regulates DCs is through the Dab2/Src/PI3K/Akt‐NF‐κB signalling axis.
RATIONALE:We and others have demonstrated that anthocyanins have antiatherogenic capability. Because intact anthocyanins are absorbed very poorly, the low level of circulating parent anthocyanins may ...not fully account for their beneficial effect. We found recently that protocatechuic acid (PCA), a metabolite of cyanidin-3 to 0-β-glucoside (Cy-3-G), has a remarkable antiatherogenic effect.
OBJECTIVE:To investigate whether mouse gut microbiota metabolizes Cy-3-G into PCA and to determine whether and how PCA contributes to the antiatherogenic potency of its precursor, Cy-3-G.
METHODS AND RESULTS:PCA was determined as a gut microbiota metabolite of Cy-3-G in ApoE mice, verified by the utilization of antibiotics to eliminate gut microbiota and further microbiota acquisition. PCA but not Cy-3-G at physiologically reachable concentrations promoted cholesterol efflux from macrophages and macrophage ABCA1 and ABCG1 expression. By conducting a miRNA microarray screening, we revealed that expression of miRNA-10b in macrophages can be reduced by PCA. Functional analyses demonstrated that miRNA-10b directly represses ABCA1 and ABCG1 and negatively regulates cholesterol efflux from murine- and human-derived macrophages. Further in vitro and ex vivo analyses verified that PCA accelerates macrophage cholesterol efflux, correlating with the regulation of miRNA-10b-ABCA1/ABCG1 cascade, whereas Cy-3-G consumption promoted macrophage RCT and regressed atherosclerotic lesion in a gut microbiotaendependent manner.
CONCLUSIONS:PCA, as the gut microbiota metabolite of Cy-3-G, exerts the antiatherogenic effect partially through this newly defined miRNA-10b-ABCA1/ABCG1-cholesterol efflux signaling cascade. Thus, gut microbiota is a potential novel target for atherosclerosis prevention and treatment.
Sustained low-grade inflammation mediated by non-resolving inflammatory monocytes has long been suspected in the pathogenesis of atherosclerosis; however, the molecular mechanisms responsible for the ...sustainment of non-resolving inflammatory monocytes during atherosclerosis are poorly understood. Here we observe that subclinical endotoxemia, often seen in humans with chronic inflammation, aggravates murine atherosclerosis through programming monocytes into a non-resolving inflammatory state with elevated Ly6C, CCR5, MCP-1 and reduced SR-B1. The sustainment of inflammatory monocytes is due to the disruption of homeostatic tolerance through the elevation of miR-24 and reduction of the key negative-feedback regulator IRAK-M. miR-24 reduces the levels of Smad4 required for the expression of IRAK-M and also downregulates key lipid-processing molecule SR-B1. IRAK-M deficiency in turn leads to elevated miR-24 levels, sustains disruption of monocyte homeostasis and aggravates atherosclerosis. Our data define an integrated feedback circuit in monocytes and its disruption may lead to non-resolving low-grade inflammation conducive to atherosclerosis.
Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. Here, ...we hypothesized that cyanidin 3-glucoside (C3G), a typical anthocyanin reported to possess potent anti-inflammatory properties, would ameliorate obesity-associated inflammation and metabolic disorders, such as insulin resistance and hepatic steatosis in mouse models of diabesity. Male C57BL/6J obese mice fed a high-fat diet for 12 weeks and genetically diabetic db/db mice at an age of 6 weeks received dietary C3G supplementation (0.2%) for 5 weeks. We found that dietary C3G lowered fasting glucose levels and markedly improved the insulin sensitivity in both high-fat diet fed and db/db mice as compared with unsupplemented controls. White adipose tissue messenger RNA levels and serum concentrations of inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1) were reduced by C3G, as did macrophage infiltration in adipose tissue. Concomitantly, hepatic triglyceride content and steatosis were alleviated by C3G. Moreover, C3G treatment decreased c-Jun N-terminal kinase activation and promoted phosphorylation and nuclear exclusion of forkhead box O1 after refeeding. These findings clearly indicate that C3G has significant potency in antidiabetic effects by modulating the c-Jun N-terminal kinase/forkhead box O1 signaling pathway and the related inflammatory adipocytokines.
Numerous clinical trials have confirmed that supplementation with purified anthocyanins has favorable effects on metabolic diseases, but the dose-response of dyslipidemia to anthocyanin ...supplementation remains unclear. This study aimed to investigate the effect of anthocyanin supplementation in different doses on lipid profile.
We randomly assigned 176 dyslipidemic subjects aged 35-70 to three purified anthocyanin groups (40 mg/day, n = 45; 80 mg/day, n = 42; 320 mg/day, n = 43) and a placebo group (n = 46). Anthropometric parameters, serum lipid profiles, and cholesterol efflux capacity (CEC) were measured at baseline, and at the end of 6 and 12 weeks.
After 12 weeks of supplementation, significant differences in CEC (P = 0.033), high-density lipoprotein cholesterol (HDL-C) (P = 0.043), and apolipoprotein A-I (ApoA-I) (P = 0.022) were observed between four groups. Compared with placebo, 320 mg/day anthocyanin significantly increased CEC (35.8%, 95% CI: 11.5-60.2%; P = 0.004), HDL-C (0.07 mmol/L, 95% CI: 0.01-0.14; P = 0.003), and ApoA-I (0.07 g/L, 95% CI: 0.01-0.12; P = 0.008). Linear trend analysis showed that anthocyanin supplementation has a strong dose-response relationship with CEC (P = 0.002), HDL-C (P = 0.038), and ApoA-I (P = 0.023). Moreover, the enhancement of CEC showed positive correlations with the increase in HDL-C (r = 0.215, P < 0.01) and APOA-I (r = 0.327, P < 0.01).
Anthocyanin supplementation at 0-320 mg/day for 12 weeks enhances CEC in a dose-response manner in dyslipidemic subjects. Anthocyanin supplementation doses of 80-320 mg/day can improve serum HDL-C levels and HDL-induced CEC.
Polyphenols, including anthocyanins, from various plant foods are effective in the prevention of atherosclerosis in animal and human studies. Protocatechuic acid (PCA), a major metabolite of ...anthocyanins, has been found to possess the anti-carcinogenic effect, whereas the in vivo effect of PCA as an anti-atherosclerotic agent remains unknown. We demonstrated herein that PCA inhibited monocyte adhesion to tumor necrosis factor-α (TNF-α)-activated mouse aortic endothelial cells, associated with the inhibition of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression. Furthermore, PCA inhibited the nuclear content of p65, a subunit of nuclear factor-κB (NF-κB), along with reduced NF-κB binding activity. Finally, PCA administration in the apolipoprotein E (ApoE)-deficient mouse model reduced aortic VCAM-1 and ICAM-1 expression, NF-κB activity, and plasma-soluble VCAM-1 and ICAM-1 levels, with inhibiting atherosclerosis development. We suggest that PCA possesses the anti-atherogenic effect at least partially via its anti-inflammatory activity.
Anthocyanins widely present in human diet and have a variety of health effects. This study investigates the anticancer effects of an anthocyanin-rich extract from black rice (AEBR) on breast cancer ...cells in vitro and in vivo. AEBR reduced the viability of breast cancer cell lines MCF-7 (ER+, HER2/neu-), MDA-MB-231 (ER-, HER2/neu-), and MDA-MB-453 (ER-, HER2/neu+) and induced apoptosis in MDA-MB-453 cells via the intrinsic pathway in vitro by activating caspase cascade, cleaving poly (ADP-ribose) polymerase (PARP), depolarizing mitochondrial membrane potential, and releasing cytochrome C. Oral administration of AEBR (100 mg/kg/day) to BALB/c nude mice bearing MDA-MB-453 cell xenografts significantly suppressed tumor growth and angiogenesis by suppressing the expression of angiogenesis factors MMP-9, MMP-2, and uPA in tumor tissue. Altogether, this study suggests the anticancer effects of AEBR against human breast cancer cells in vitro and in vivo by inducing apoptosis and suppressing angiogenesis.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown.
In a short-term crossover ...study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8).
Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P < 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs -1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P < 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P < 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model.
Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.
Adropin, a secretory signal peptide, has shown beneficial effects on improving glucose homeostasis and dyslipidemia. However, whether this peptide affects nonalcoholic steatohepatitis (NASH) has ...remained unclear. In this study, the serum adropin levels, liver injury and oxidative stress were measured in diet-induced NASH mice. Adropin knock-out mice and palmitate treated primary hepatic cells were used to investigate the influence of adropin on liver injury. Our results show that serum adropin levels were decreased and negatively correlated with liver injury in NASH mice. Knockout of adropin significantly exacerbated hepatic steatosis, inflammatory responses and fibrosis in mice after either methionine-choline deficient diet (MCD) or western diet (WD) feeding. And the treatment with adropin bioactive peptides ameliorated NASH progression in mice. Adropin alleviated hepatocyte injury by upregulating the expression of Gclc, Gclm, and Gpx1 in a manner dependent on Nrf2 transcriptional activity and by increasing the glutathione (GSH) levels. And adropin significantly increased CBP expression and promoted its binding with Nrf2, which enhanced Nrf2 transcriptional activity. Furthermore, AAV8-mediated overexpression of hepatic Nrf2 expression functionally restored the liver injury induced by adropin-deficiency MCD-fed mice. These findings provide evidence that adropin activates Nrf2 signaling and plays a protective role in liver injury of NASH and therefore might represent a novel target for the prevention and treatment of NASH.
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