Previous studies demonstrated that oral administration of Saskatoon berry powder (SBp) reduced fasting plasma glucose (FPG), insulin resistance, lipids, and inflammatory markers in diet-induced ...insulin resistant rodents. Mechanism for the beneficial effects of SB remains unclear. The present study examined the effects of high fat-high sucrose (HFHS) diet supplemented with or without 5% SBp, cyanidin-3-glucoside (C3G, an anthocyanin rich in SBp) at a dosage of C3G in 5% SBp, or equimolar concentration of protocatechuic acid (PCA, a relatively stable metabolite of C3G) for 11 weeks on FPG, cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), circulatory inflammatory markers, fecal microbiota, and short chain fatty acids in mice. HFHS diet significantly enhanced FPG, insulin, HOMA-IR, lipids and inflammatory markers, but reduced the abundance of fecal Bacteroidetes, Muribaculaceae and propionate compared to low fat diet. Supplementation of SBp, C3G or PCA significantly attenuated HFHS diet induced metabolic and inflammatory markers, and increased the abundances of fecal Muribaculaceae and propionate compared to HFHS diet alone. The abundances of fecal Muribaculaceae negatively correlated with FPG, lipids, HOMA-IR and inflammatory markers in the mice. The abundances of fecal propionate positively correlated with fecal Muribaculaceae and negatively correlated with the metabolic and inflammatory markers. The findings suggest that C3G in SBp and PCA contribute to the metabolic and anti-inflammatory effect of SBp in mice. The increases in fecal Muribaculaceae and propionate may play important regulatory roles in the anti-diabetic and anti-inflammatory benefits of SBp, C3G, and PCA in mice.
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Cardiovascular diseases are the predominant cause of death in patients with diabetes mellitus. Underlying mechanism for the susceptibility of diabetic patients to cardiovascular diseases remains ...unclear. Elevated oxidative stress was detected in diabetic patients and in animal models of diabetes. Hyperglycemia, oxidatively modified atherogenic lipoproteins, and advanced glycation end products are linked to oxidative stress in diabetes. Mitochondria are one of major sources of reactive oxygen species (ROS) in cells. Mitochondrial dysfunction increases electron leak and the generation of ROS from the mitochondrial respiratory chain (MRC). High levels of glucose and lipids impair the activities of MRC complex enzymes. NADPH oxidase (NOX) generates superoxide from NADPH in cells. Increased NOX activity was detected in diabetic patients. Hyperglycemia and hyperlipidemia increased the expression of NOX in vascular endothelial cells. Accumulated lines of evidence indicate that oxidative stress induced by excessive ROS production is linked to many processes associated with diabetic cardiovascular complications. Overproduction of ROS resulting from mitochondrial dysfunction or NOX activation is associated with uncoupling of endothelial nitric oxide synthase, which leads to reduced production of nitric oxide and endothelial-dependent vasodilation. Gene silence or inhibitor of NOX reduced oxidized or glycated LDL-induced expression of plasminogen activator inhibitor-1 in endothelial cells. Statins, hypoglycemic agents, and exercise may reduce oxidative stress in diabetic patients through the reduction of NOX activity or the improvement of mitochondrial function, which may prevent or postpone the development of cardiovascular complications.
Accumulated lines of evidence demonstrate that the gut microbiota plays a critical role in metabolism, inflammation and the pathophysiology of many chronic diseases ....
The present study examined the impact of Saskatoon berry powder (SBp) on insulin resistance, inflammation and intestinal microbiota in diet-induced obese mice. Male C57 BL/6 J mice were fed control ...diet, high fat-high sucrose (HFHS) diet or HFHS+5% SBp (HFHS+B) diet for 15 weeks. The composition of fecal bacterial community was characterized using the Illumina sequencing of V4 region of 16S rRNA gene. HFHS diet increased body weight, fasting plasma glucose, cholesterol, triglycerides, insulin, homeostatic model assessment-insulin resistance, monocyte adhesion, tumor necrosis factor-α, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, intracellular cell adhesion molecule-1, urokinase plasminogen activator and its receptor in plasma or aortae compared to the control diet. HFHS+B diet postponed the increase in body weight, suppressed HFHS diet-induced disorders in the metabolic and inflammatory variables. The ratio of Firmicutes/Bacteroidetes in the HFHS group was higher than that in the control group (P<.01), and that in the HFHS+B group was lower than that in the HFHS group (P<.05). The abundances of S24–7 family negatively correlated with body weight and tested metabolic or inflammatory variables. The results suggest that SBp attenuated HFHS diet-induced metabolic disorders and vascular inflammation in gut microbiota in mice.
Previous studies indicated that North American wild rice (WIR) reduced atherosclerosis and vascular inflammation in low-density lipoprotein receptor knockout mice. The effects of WIR on hyperglycemia ...in diabetic animal models have not been documented. The present study aims to determine the impact of WIR on glucose metabolism in high-fat (HF)-induced diabetic mice and a key modulator. Male C57 BL/J6 mice were treated with a control diet and a HF diet supplemented with 26% (weight/weight, a substitute for carbohydrates in the diet) of WIR or white rice (WHR) (n = 8/group) for 11 weeks. HF + WHR diet significantly increased fasting plasma glucose, cholesterol, triglycerides, insulin, insulin resistance, monocyte adhesion, and the levels of relevant inflammatory mediators (tumor necrotic factor-α, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1) in mice compared to the control diet (p < 0.01). HF + WIR significantly reduced HF diet-induced metabolic and inflammatory changes compared to the HF + WHR diet (p < 0.01). Metabolomics analysis indicated that an array of metabolites related to glucose metabolism was significantly more abundant in WIR than in WHR, including adenosine 5′-monophosphate (AMP), a potent agonist for AMP-activated protein kinase or AMPK. WIR normalized HF diet-induced reduction in the abundance of phospho-AMPKα in skeletal muscle, liver, and adipose tissue from the mice. The findings for the first time demonstrated that WIR decreased HF diet-induced hyperglycemia in mice compared to WHR. The metabolic benefits of WIR may result, at least in part, from the activation of AMPKα in insulin-sensitive tissue in the mice.
Non-alcoholic fatty liver disease is a common metabolic disorder associated with insulin resistance and lacks a specific treatment. Our previous studies demonstrated that freeze-dried Saskatoon berry ...powder (SBp) reduced high fat-high sucrose (HFHS) diet-induced hyperglycemia and insulin resistance in mice. The present study examined the effect of SBp and one of its active components, cyanidin-3-glucoside (C3G), on hepatic steatosis in mice fed with HFHS diet for 10 weeks. HFHS diet significantly increased fasting plasma glucose, cholesterol, triglycerides, insulin resistance, inflammatory markers (tumor necrosis factor-α, monocyte chemotactic protein-1, plasminogen activator inbitor-1), alanine aminotransferase activity, and monocyte adhesion compared to control diet. In the liver, HFHS diet increased steatosis, lipid accumulation, collagen deposition, and the abundance of patatin-like phospholipase domain-containing 3, CCAAT-enhancer-binding protein homologous protein, toll-like receptor-4, and macrophage marker. Supplementation with SBp (5%) or C3G in an amount corresponding to that in 5% SBp to HFHS diet had similar effects to reduced fasting plasma glucose, liver steatosis, enzyme activity, lipid, collagen and macrophage deposition, hyperglycemia, hyperlipidemia, insulin resistance, monocyte adhesion, markers related to liver steatosis, inflammation, oxidative or endoplasmic reticulum stress in the peripheral circulation and/or liver compared to mice fed with HFHS diet alone. No significant difference in the studied variables was detected between mice treated with HFHS+SBp and C3G diet. The results suggest that SBp or C3G administration attenuates HFHS diet-induced liver steatosis in addition to insulin resistance and chronic inflammation in mice. C3G may contribute to the beneficial effects of SBp.
•High fat-high sucrose (HFHS) diet increased liver steatosis and insulin resistance in mice.•Saskatoon berry powder (SBp) attenuated steatosis and ALT activity in mice fed with HFHS diet.•SBp decreased insulin resistance and vascular inflammation in mice receiving HFHS diet.•Cyanidin-3-glucose mimics the effects of SBp on liver abnormalities in HFHS diet-fed mice.•Cyanidin-3-glucose reduced insulin resistance and vascular inflammation in HFHS diet-fed mice.
The binding interactions of bovine lactoferrin (BLF) with two flavonoids dihydromyricetin (DMY) and myricetin (MY) were investigated by the multi-spectroscopic, microscale thermophoresis (MST) ...techniques, molecular docking, and then their antioxidant activities were studied by detection of free radical scavenging activity against DPPH. Results of UV–vis and fluorescence spectroscopies showed that DMY/MY and BLF formed the ground state complex through the static quenching mechanism. Moreover, MY with more planar stereochemical structure had higher affinity for BLF than DMY with twisted stereochemical structure, according to the binding constant (Kb), free energy change (ΔG°), dissociation constant (Kd) and donor-acceptor distance (r). Thermodynamic parameters revealed that hydrogen bond and van der Waals force were major forces in the formation of BLF-DMY complex, while hydrophobic interactions played major roles in the formation of BLF-DMY complex. The circular dichroism (CD) study indicated that MY induced more conformational change in BLF than DMY. Furthermore, molecular modeling provided insights into the difference of binding interactions between BLF and two flavonoids. Finally, the radical scavenging activity assays indicated the presence of BLF delayed the decrease in antioxidant capacities of two flavonoids. These results were helpful to understand the binding mechanism and biological effects of non-covalent BLF-flavonoid interaction.
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•Dihydromyricetin and myricetin quench the fluorescence of bovine lactoferrin through a static quenching mechanism.•Myricetin has a stronger affinity to bovine lactoferrin than dihydromyricetin.•Myricetin induced more conformation changes in BLF than dihydromyricetin.•Antioxidant activity of flavonoids and their complexes with bovine lactoferrin were assessed.
The present study assessed the effects of freeze-dried cyanidin-3-glucoside (C3G), an anthocyanin enriched in dark-red berries, compared to Saskatoon berry powder (SBp) on metabolism, inflammatory ...markers and gut microbiota in high fat-high sucrose (HFHS) diet-induced insulin-resistant mice. Male C57 BL/6J mice received control, HFHS, HFHS + SBp (8.0 g/kg/day) or HFHS + C3G (7.2 mg/kg/day, equivalent C3G in SBp) diet for 11 weeks. The HFHS diet significantly increased plasma levels of glucose, cholesterol, triglycerides, insulin resistance and inflammatory markers. The HFHS + SBp diet increased the Bacteroidetes/Firmicutes (B/F) ratio and relative abundance of Muriculaceae family bacteria in mouse feces detected using 16S rRNA gene sequencing. The HFHS + SBp or HFHS + C3G diet attenuated glucose, lipids, insulin resistance and inflammatory markers, and increased the B/F ratio and Muriculaceae relative abundance compared to the HFHS diet alone. The relative abundances of Muriculaceae negatively correlated with body weight, glucose, lipids, insulin resistance and inflammatory mediators. Functional predication analysis suggested that the HFHS diet upregulated gut bacteria genes involved in inflammation, and downregulated bacteria involved in metabolism. C3G and SBp partially neutralized HFHS diet-induced alterations of gut bacteria. The results suggest that C3G is a potential prebiotic, mitigating HFHS diet-induced disorders in metabolism, inflammation and gut dysbiosis, and that C3G contributes to the metabolic beneficial effects of SBp.
Biofortification using inorganic selenium has become an effective strategy to enhance selenium content in crops. In the present study, the effects of selenium biofortification on the chemical ...composition and antioxidant capacity of black soybean (BS) during germination were studied. The contents of selenium, total sugar, vitamin C, γ‐aminobutyric acid, total polyphenols, and total flavonoids in selenium biofortified germinated black soybeans (GBS‐Se) significantly increased compared to germinated black soybeans (GBS). However, the contents of soluble protein, fat, and reducing sugar were decreased, while fatty acid composition was not significantly different between GBS and BS. HPLC analysis showed that 12 phenolic acids of all samples, which mainly existed in free forms. Their contents increased at low concentration of selenium and decreased along with the rise of selenium concentrations. The antioxidant activity of GBS‐Se as analyzed by Pearson correlation analysis positively correlated with the accumulation of phenolic substances. Principal component analysis (PCA) showed that GBS and GBS‐Se were significantly different from BS. Moreover, the physicochemical indexes of GBS showed regularly changes with increasing selenium content, and those of GBS‐Se50 and GBS‐Se75 were significantly different from GBS. The results provide a systematic evaluation on the effect of selenium fortification on the germination of seeds and useful information for the development of Se‐enriched functional foods.
Practical Application
The organic selenium black soybean (BS) produced by the germination method can be directly processed and eaten to improve human health. In addition, complexes of organic selenium, vitamin C, and γ‐aminobutyric acid of germinated BS can be developed into functional substances and applied to food or health products as functional ingredient and/or natural antioxidant supplements.
Intake of whole grain foods is associated with improving metabolic profile compared to refined grain products, but the underlying mechanism remains unclear. The present study examined the effects of ...brown rice (BRR) or germinated brown rice (GBR) supplementation on fecal short-chain fatty acids (SCFAs), and relationship with gut microbiota, metabolism and inflammation in high fat (HF)-diet-fed mice. The results demonstrated that an HF diet supplemented with BRR or GBR comparably increased the abundance of fecal isobutyric acid compared to that in mice receiving HF+white rice (WHR) diet (p < 0.01). The abundance of valeric acid in HF+GBR-diet-fed mice was higher than those receiving HF+WHR diet (p < 0.05). The abundances of fecal isobutyric acid negatively correlated with fasting plasma glucose, insulin, cholesterol, triglycerides, tumor necrosis factor-α, plasminogen activator inhibit-1, monocyte chemotactic protein-1 and homeostatic model assessment of insulin resistance (p < 0.01). The abundance of valeric acids negatively correlated with insulin resistance (p < 0.05). The abundances of isobutyric acid positively correlated with Lactobacillus, but negatively correlated with Dubosiella genus bacteria (p < 0.05). The findings demonstrated that the increases in SCFAs in the feces of BRR and GBR-treated mice were associated with improvements in gut microbiome, metabolic and inflammatory profile, which may contribute to the antidiabetic and anti-inflammatory effects of the whole grains in HF-diet-fed mice.
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