BackgroundQuercetin derivatives in onions have been regarded as the most important flavonoids to improve diabetic status in cells and animal models. The present study was aimed to examine the hypoglycemic and insulin-sensitizing capacity of onion peel extract (OPE) containing high quercetin in high fat diet/streptozotocin-induced diabetic rats and to elucidate the mechanism of its insulin-sensitizing effect.MethodsMale Sprague-Dawley rats were fed the AIN-93G diet modified to contain 41.2% fat and intraperitoneally injected with a single dose of streptozotocin (40 mg/kg body weight). One week after injection, the rats with fasting blood glucose levels above 126 mg/dL were randomly divided into 4 groups to treat with high fat diet containing 0 (diabetic control), 0.5, or 1% of OPE or 0.1% quercetin (quercetin equivalent to 1% of OPE) for 8 weeks. To investigate the mechanism for the effects of OPE, we examined biochemical parameters (insulin sensitivity and oxidative stresses) and protein and gene expressions (pro-inflammatory cytokines and receptors).ResultsCompared to the diabetic control, hypoglycemic and insulin-sensitizing capability of 1% OPE were demonstrated by significant improvement of glucose tolerance as expressed in incremental area under the curve (P = 0.0148). The insulin-sensitizing effect of OPE was further supported by increased glycogen levels in liver and skeletal muscle (P < 0.0001 and P = 0.0089, respectively). Quantitative RT-PCR analysis showed increased expression of insulin receptor (P = 0.0408) and GLUT4 (P = 0.0346) in muscle tissues. The oxidative stress, as assessed by superoxide dismutase activity and malondialdehyde formation, plasma free fatty acids, and hepatic protein expressions of IL-6 were significantly reduced by 1% OPE administration (P = 0.0393, 0.0237, 0.0148 and 0.0025, respectively).ConclusionOPE might improve glucose response and insulin resistance associated with type 2 diabetes by alleviating metabolic dysregulation of free fatty acids, suppressing oxidative stress, up-regulating glucose uptake at peripheral tissues, and/or down-regulating inflammatory gene expression in liver. Moreover, in most cases, OPE showed greater potency than pure quercetin equivalent. These findings provide a basis for the use of onion peel to improve insulin insensitivity in type 2 diabetes.

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BackgroundHigh level of serum cholesterol is considered to be a major risk factor for cardiovascular disease (CVD). A double-blinded, randomized, placebo-controlled trial was performed to test the hypothesis that a daily intake of Chlorella may improve serum lipid profile through enhancement of serum carotenoid concentration in mildly hypercholesterolemic subjects.MethodsEligible subjects (n = 63) were randomized to either Chlorella (5 g/day) or placebo for a double-blinded trial with a 2-week lead-in period and a 4-week intervention period. Serum triglycerides, total cholesterol, lipoproteins, apolipoproteins and carotenoids were assessed at the beginning and the end of the trial.ResultsCompared with the control group, the Chlorella group exhibited remarkable changes in total cholesterol (Chlorella −1.6%; placebo 0.03%; P = 0.036), triglycerides (Chlorella −10.3%; placebo 11.9%; P = 0.002), lutein/zeaxanthin (Chlorella 89.6%; placebo −1.7%; P < 0.0001), and α-carotene (Chlorella 163.6%; placebo 15%; P < 0.0001). Improvement of serum lipids was supported by significant reductions of very low-density lipoprotein cholesterol (Chlorella −11%; placebo 11.8%; P = 0.006), apolipoprotein B (Chlorella −1.5%; placebo 1.7%; P = 0.044), non high-density lipoprotein (Chlorella −2.6%; placebo −0.5%; P = 0.032), and high-density lipoprotein/triglycerides (Chlorella 4.0%; placebo −9.5%; P = 0.023), suggesting an inhibitory effect of Chlorella on the intestinal absorption of dietary and endogenous lipids. Further, the changes of serum lipids appeared to be associated with the changes of serum carotenoids.ConclusionDaily consumption of Chlorella supplements provided the potential of health benefits reducing serum lipid risk factors, mainly triglycerides and total cholesterol, in mildly hypercholesterolemic subjects. The effect was related to carotenoid consumption.Trial registrationWHO International Clinical Trials Registry Platform KCT0000259.

It is important to understand the association between oxidative stress-related parameters and to evaluate their status in advance of chronic disease development. Further development towards disease can then be prevented by dietary antioxidants. The present study was aimed at assessing the relationship between diet quality, blood antioxidants, and oxidative damage to determine whether the association between these markers differs by oxidative stress status. For a cross-sectional analysis, we used data and samples of baseline information from a prospective cohort study. A total of 1229 eligible adults were classified into apparently healthy subjects (66.5%) and those with oxidative stress conditions (35.5%). Diet quality was assessed using the recommended food score (RFS). Plasma carotenoids (blood antioxidants) and blood/urinary malondialdehyde (MDA; oxidative damage) were determined by high-performance liquid chromatography. We found that the healthy group was younger, and they had a lower RFS and plasma MDA level and higher plasma carotenoids compared to the oxidative stress condition group. This result is probably due to the quenching of the oxidative response in the tissues of those people. A positive association of RFS with plasma carotenoids (total and β-carotene) was found in both groups, suggesting that carotenoids are a robust reflection of diet quality. Negative associations were observed between plasma MDA and RFS in the oxidative stress condition group and between urinary MDA and plasma zeaxanthin in the healthy group. Erythrocyte MDA was positively associated with plasma carotenoids (total, lutein, zeaxanthin, β-cryptoxanthin, and α- and β-carotene), regardless of health condition, probably also as a result of the use of carotenoids as antioxidants. In conclusion, these results indicate that the above three factors may be associated with the oxidative stress response and depend on the oxidative status. Furthermore, it was also suggested that erythrocytes are important in the oxidative stress response and the quenching of this response is represented in plasma carotenoids.

Reactive oxygen species are important risk factors for age-related diseases, but they also act as signaling factors for endogenous antioxidative defense. The hypothesis that a multi-micronutrient supplement with nutritional doses of antioxidant nutrients and phytochemicals (MP) may provide protection against oxidative damage and maintain the endogenous antioxidant defense capacity was assessed in subjects with a habitually low intake of fruits and vegetables. In a randomized, placebo-controlled, and parallel designed trial, 89 eligible subjects were assigned to either placebo or MP for eight weeks. Eighty subjects have completed the protocol and included for the analysis. MP treatment was superior at increasing serum folate (p < 0.0001) and resistance to DNA damage (p = 0.006, tail intensity; p = 0.030, tail moment by comet assay), and LDL oxidation (p = 0.009) compared with the placebo. Moreover, the endogenous oxidative defense capacity was not weakened after MP supplementation, as determined by the levels of glutathione peroxidase (p = 0.442), catalase (p = 0.686), and superoxide dismutase (p = 0.804). The serum folate level was negatively correlated with DNA damage (r = −0.376, p = 0.001 for tail density; r = −0.329, p = 0.003 for tail moment), but no correlation was found with LDL oxidation (r = −0.123, p = 0.275). These results suggest that MP use in healthy subjects with habitually low dietary fruit and vegetable intake may be beneficial in providing resistance to oxidative damage to DNA and LDL without suppressing the endogenous defense mechanisms.

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The vascular endothelium is a favorite early target of cardiovascular risk factors, including cigarette smoking. Here, we investigated the synergistic effects of Sanghuang–Danshen (SD) bioactives on vascular stiffness in a controlled clinical trial of healthy chronic smokers (n = 72). Relative to placebo, 4-week SD consumption at 900 mg/day improves pulse wave velocity (p = 0.0497), reduces systolic blood pressure (peripheral, p = 0.0008; brachial, p = 0.0046; and ankle, p = 0.0066), and increases endothelial nitric oxide synthase activation (p < 0.0001). We then mapped all differential markers obtained from the clinical data, Affymetrix microarray, and 1H NMR metabolomics, together with 12 SD bioactives, onto the network platform termed the context-oriented directed associations. The resulting vascular subnetwork demonstrates that ellagic acid, caffeic acid, protocatechuic acid, cryptotanshinone, tanshinone I, and tanshinone IIA are linked to NOS3, ARG2, and EDN1 for vascular dilation, implicated with arginine/proline metabolism. They are also linked to SUCLG1, CYP1A1, and succinate related to the mitochondrial metabolism and detoxification, implicated with various metabolic pathways. These results could explain the synergistic action mechanisms of SD bioactives in the regulation of vascular endothelial dilation and metabolism, confirming the potential of SD in improving vascular stiffness and blood pressure in healthy smokers.