Euglena gracilis produce high amounts of algal β-1,3-glucan, which evoke an immune response when consumed. This study investigated the effect of supplementation with a proprietary Euglena gracilis fermentate (BG), containing greater than 50% β-1,3-glucan, on immune function as measured by self-reported changes in upper respiratory tract infection (URTI) symptoms. Thirty-four healthy, endurance-trained participants were randomized and received either 367 mg of BG or placebo (PLA) for 90 days. Symptoms were assessed by the 24-item Wisconsin Upper Respiratory Symptom Survey and safety via clinical chemistry, hematology, vitals, and adverse event reporting. Participants supplemented with BG over 90 days reported fewer sick days (BG: 1.46 ± 1.01; PLA: 4.79 ± 1.47 days; p = 0.041), fewer URTI symptoms (BG: 12.62 ± 5.92; PLA: 42.29 ± 13.17; p = 0.029), fewer symptom days (BG: 5.46 ± 1.89; PLA: 15.43 ± 4.59 days; p = 0.019), fewer episodes (BG: 2.62 ± 0.67; PLA: 4.79 ± 0.67; p = 0.032), and lower global severity measured as area under curve for URTI symptoms (BG: 17.50 ± 8.41; PLA: 89.79 ± 38.92; p = 0.0499) per person compared to placebo. Sick days, symptoms, and global severity were significantly (p < 0.05) fewer over 30 days in the BG group compared to PLA. All safety outcomes were within clinically normal ranges. The study provides evidence that supplementation with a proprietary Euglena gracilis fermentate containing greater than 50% β-1,3-glucan may reduce and prevent URTI symptoms, providing immune support and protecting overall health. Full article

The fatty acid, lauric acid (‘C12’), and the amino acid, tryptophan (‘Trp’), when given intraduodenally at loads that individually do not affect energy intake, have recently been shown to stimulate plasma cholecystokinin, suppress ghrelin and reduce energy intake much more markedly when combined. Both fatty acids and amino acids stimulate insulin secretion by distinct mechanisms; fatty acids enhance glucose-stimulated insulin secretion, while amino acids may have a direct effect on pancreatic β cells. Therefore, it is possible that, by combining these nutrients, their effects to lower blood glucose may be enhanced. We have investigated the potential for the combination of C12 and Trp to have additive effects to reduce blood glucose. To address this question, plasma concentrations of glucose, insulin and glucagon were measured in 16 healthy, lean males during duodenal infusions of saline (control), C12 (0.3 kcal/min), Trp (0.1 kcal/min), or C12+Trp (0.4 kcal/min), for 90 min. Both C12 and C12+Trp moderately reduced plasma glucose compared with control (p < 0.05). C12+Trp, but not C12 or Trp, stimulated insulin and increased the insulin-to-glucose ratio (p < 0.05). There was no effect on plasma glucagon. In conclusion, combined intraduodenal administration of C12 and Trp reduced fasting glucose in healthy men, and this decrease was driven primarily by C12. The effects of these nutrients on postprandial blood glucose and elevated fasting blood glucose in type 2 diabetes warrant evaluation. Full article

Background: Docosahexaenoic acid (DHA) is an essential polyunsaturated fatty acid compound present in deep water fishes and dietary supplements, with a wide spectrum of potential health benefits, ranging from neurological to anti-inflammatory. Methods: Due to the fact that DHA is considered a breast cancer risk reducer, we examined the impact of DHA on MCF-7 breast cancer cells’ viability and its inhibitory properties on protein tyrosine phosphatase 1B (PTP1B), a pro-oncogenic phosphatase. Results: We found that DHA is able to lower both the enzymatic activity of PTP1B phosphatase and the viability of MCF-7 breast cancer cells. We showed that unsaturated DHA possesses a significantly higher inhibitory activity toward PTP1B in comparison to similar fatty acids. We also performed a computational analysis of DHA binding to PTP1B and discovered that it is able to bind to an allosteric binding site. Conclusions: Utilizing both a recombinant enzyme and cellular models, we demonstrated that DHA can be considered a potential pharmacological agent for the prevention of breast cancer. Full article

Our aim was to investigate whether hot water extract (CLW) of Curcuma longa L. could prevent non-alcoholic fatty liver disease (NAFLD). HepG2 cells were treated with free fatty acid (FFA) mixture (oleic acid: palmitic acid, 2:1) for 24 h to stimulate in vitro fatty liver. In addition, C57BL/6 mice were fed 60 kcal% high-fat (HF) diet for eight weeks to induce fatty liver in vivo. Intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) productions were increased by FFA and HF-diet, but supplementation with CLW significantly decreased these levels. CLW treatment ameliorated antioxidant activities that were suppressed by exposure to the FFA and HF-diet. Cluster of differentiation 36 (CD36) and fatty acid transport proteins (FATP2 and FATP5) were increased in HF-diet groups, while CLW suppressed their expression levels. Moreover, sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-coenzyme A carboxylase (ACC), and fatty acid synthase (FAS) expression levels were down-regulated in the CLW groups compared to HF-diet groups. On the other hand, 5′ adenosine monophosphate-activated protein kinase (AMPK), Peroxisome proliferator-activated receptor alpha (PPAR-α), and carnitine palmitoyltransferase 1 (CPT-1) expressions were up-regulated in the CLW groups. HF-diet fed mice showed high hepatic triglycerides (TG) content compared to the normal diet mice. However, the administration of CLW restored the hepatic TG level, indicating an inhibitory effect against lipid accumulation by CLW. These results suggest that CLW could be a potentially useful agent for the prevention of NAFLD through modulating fatty acid uptake. Full article

Rhodiola crenulata (R) and Cordyceps sinensis (C) are commonly used herbs that promote health in traditional Chinese medicine. These two herbs have also been shown to exhibit anti-inflammation and antioxidant functions. Regular endurance training reveals potent endurance capacity, body composition improvement, and metabolic-related biomarker benefits. However, it is not known whether the combination of Rhodiola crenulata and Cordyceps sinensis (RC) supplementation during endurance training provides additive health benefits. The purpose of this study was to investigate the effects of 8-week endurance training plus RC supplementation on body composition, oxidative stress, and metabolic biomarkers in young sedentary adults. Methods: Fourteen young sedentary adults (8M/6F) participated in this double-blind randomized controlled study. Participants were assigned to exercise training with placebo groups (PLA, n = 7, 4M/3F; age: 21.4 ± 0.4 years) and exercise training with the RC group (RC, 20 mg/kg/day; n = 7, 4M/3F; age: 21.7 ± 0.4 years). Both groups received identical exercise training for eight weeks. The body composition, circulating oxidative stress, and blood metabolic biomarkers were measured before and after the 8-week intervention. Results: Improvement in body composition profiles were significantly greater in the RC group (body weight: p = 0.044, BMI: p = 0.003, upper extremity fat mass: p = 0.032, lower extremity muscle mass: p = 0.029, trunk fat mass: p = 0.011) compared to the PLA group after training. The blood lipid profile and systemic oxidative stress makers (thiobarbituric reactive substanceand total antioxidant capacity) did not differ between groups. Although endurance training markedly improved endurance capacity and glycemic control ability (i.e., fast blood glucose, insulin, and HOMA index), there were no differences in these variables between treatments. Conclusions: In this preliminary investigation, we demonstrated that an 8-week RC supplementation (20 mg/kg/day) faintly enhanced endurance training-induced positive adaptations in body composition in young sedentary individuals, whereas the blood lipid profile and systemic oxidative stress states were not altered after such intervention. Full article

Falcarinol (FaOH) and falcarindiol (FaDOH) are cytotoxic and anti-inflammatory polyacetylenic oxylipins, which are commonly found in the carrot family (Apiaceae). FaOH and FaDOH have previously demonstrated a chemopreventive effect on precursor lesions of colorectal cancer (CRC) in azoxymethane (AOM)-induced rats. The purpose of the present study was to elucidate possible mechanisms of action for the preventive effect of FaOH and FaDOH on colorectal precancerous lesions and to determine how this effect was dependent on dose. Gene expression studies performed by RT-qPCR of selected cancer biomarkers in tissue from biopsies of neoplastic tissue revealed that FaOH and FaDOH downregulated NF-κβ and its downstream inflammatory markers TNFα, IL-6, and COX-2. The dose-dependent anti-neoplastic effect of FaOH and FaDOH in AOM-induced rats was investigated in groups of 20 rats receiving a standard rat diet (SRD) supplemented with 0.16, 0.48, 1.4, 7 or 35 µg FaOH and FaDOH g⁻¹ feed in the ratio 1:1 and 20 rats were controls receiving only SRD. Analysis of aberrant crypt foci (ACF) showed that the average number of small ACF (<7 crypts) and large ACF (>7 crypts) decreased with increasing dose of FaOH and FaDOH and that this inhibitory effect on early neoplastic formation of ACF was dose-dependent, which was also the case for the total number of macroscopic neoplasms. The CRC protective effects of apiaceous vegetables are mainly due to the inhibitory effect of FaOH and FaDOH on NF-κB and its downstream inflammatory markers, especially COX-2. Full article

Functional oligosaccharides, particularly konjac mannan oligosaccharides (KMOS), can regulate glucose metabolism. However, the molecular mechanisms involved in the hypoglycemic effect of KMOS remain largely unknown. Here, the effect of KMOS supplementation on glucose homeostasis was evaluated in both high-fat diet (HFD)-fed C57BL/6J mice and high-glucosamine-induced HepG2 cells. KMOS supplementation remarkably ameliorated the fasting blood glucose, glucose tolerance, and insulin tolerance of HFD-fed mice. Abnormalities of triglyceride and glycogen metabolism in the liver induced by the HFD were reversed by KMOS supplementation. The insulin signaling pathway was activated by KMOS, with stimulation of GLUT2 membrane translocation and glucose uptake in HepG2 cells via the AMPK pathway. Moreover, KMOS suppressed p-mTOR expression and stimulated the GSK-3β/CREB pathway via the AMPK pathway. KMOS significantly upregulated leptin receptor expression and downregulated PTP1B and SOCS3 levels in the liver and brain, with a decreased serum leptin concentration. Phosphorylation of JAK2 and STAT3 in the liver was activated by KMOS supplementation, while the expressions of Sirt1, Tfam, and Pgc1-α in the brain were elevated. Conclusively, KMOS attenuated HFD-induced glucose metabolism dysfunction through the regulation of insulin resistance and leptin resistance. This finding indicates that KMOS have potential value as an anti-hyperglycemic dietary supplement. Full article

Aronia melanocarpa are a rich source of anthocyanins that have received considerable interest for their relations to human health. In this study, the anti-adipogenic effect of cyanidin-3-O-galactoside-enriched Aronia melanocarpa extract (AM-Ex) and its underlying mechanisms were investigated in an in vivo system. Five-week-old male C57BL/6N mice were randomly divided into five groups for 8-week feeding with a control diet (CD), a high-fat diet (HFD), or a HFD with 50 (AM-Ex 50), 100 (AM-Ex 100), or 200 AM-Ex (AM-Ex 200) mg/kg body weight/day. HFD-fed mice showed a significant increase in body weight compared to the CD group, and AM-Ex dose-dependently inhibited this weight gain. AM-Ex significantly reduced the food intake and the weight of white fat tissue, including epididymal fat, retroperitoneal fat, mesenteric fat, and inguinal fat. Treatment with AM-Ex (50 to 200 mg/kg) reduced serum levels of leptin, insulin, triglyceride, total cholesterol, and low density lipoprotein (LDL)-cholesterol. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that AM-Ex suppressed adipogenesis by decreasing CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor gamma coactivator-1α, acetyl-CoA carboxylase 1, ATP-citrate lyase, fatty acid synthase, and adipocyte protein 2 messenger RNA (mRNA) expressions. These results suggest that AM-Ex is potentially beneficial for the suppression of HFD-induced obesity by modulating multiple pathways associated with adipogenesis and food intake. Full article

Ecklonia cava, an edible marine brown alga (Laminariaceae), is a rich source of phlorotannins. This study aimed to investigate the anti-inflammatory effect of Ecklonia cava ethanol extract (ECE, dieckol 10.6%, w/w) on Porphyromonas gingivalis lipopolysaccharide-stimulated inflammation in RAW 264.7 cells and in ligature-induced periodontitis in rats. The levels of nitric oxide (NO) and prostaglandin E₂ were decreased by more than half on treatment with 100 μg/mL ECE. Downregulated tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 gene expression confirmed the anti-inflammatory properties of ECE. ECE treatment upregulated heme oxygenase-1 (HO-1) expression by 6.3-fold and increased HO-1/nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling decreased nuclear factor-κB (NF-κB) translocation. ECE administration (400 mg/kg) significantly reduced gingival index, restricted tooth mobility, and prevented alveolar bone loss (p < 0.05). These beneficial effects were due to decreased inflammatory cell infiltration, IL-1β production, and matrix metalloproteinase expression in gingival tissues. The ratio of receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin, a biomarker of periodontitis and osteolysis, was significantly decreased by ECE administration (p < 0.05). Thus, ECE has potential therapeutic effects for the alleviation of periodontal disease. Full article

AVFQHNCQE is an antihypertensive nonapeptide obtained from a chicken foot protein hydrolysate. The present study aims to investigate the mechanisms involved in its blood pressure (BP)-lowering effect. Male (17–20 weeks old) spontaneously hypertensive rats (SHR) were used in this study. Rats were divided into two groups and orally administered water or 10 mg/kg body weight (bw) AVFQHNCQE. One hour post-administration, animals of both groups were intra-peritoneally treated with 1 mL of saline or with 1 mL of saline containing 30 mg/kg bw Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, or with 1 mL of saline containing 5 mg/kg bw indomethacin, which is an inhibitor of prostacyclin synthesis (n = 6 per group). Systolic BP was recorded before oral administration and six hours after oral administration. In an additional experiment, SHR were administered water or 10 mg/kg bw AVFQHNCQE (n = 6 per group) and sacrificed six hours post-administration to study the mechanisms underlying the peptide anti-hypertensive effect. Moreover, the relaxation caused by AVFQHNCQE in isolated aortic rings from Sprague-Dawley rats was evaluated. The BP-lowering effect of the peptide was not changed after indomethacin administration but was completely abolished by L-NAME, which demonstrates that its anti-hypertensive effect is mediated by changes in endothelium-derived NO availability. In addition, AVFQHNCQE administration downregulated aortic gene expression of the vasoconstrictor factor endothelin-1 and the endothelial major free radical producer NADPH. Moreover, while no changes in plasma ACE activity were observed after its administration, liver GSH levels were higher in the peptide-treated group than in the water group, which demonstrates that AVFQHNCQE presents antioxidant properties. Full article

Pomegranate fruit is a functional food of high interest for human health due to its wide range of phytochemicals with antioxidant properties are implicated in the prevention of inflammation and cancer. Ellagitannins, such as punicalagin and ellagic acid, play a role as anti-atherogenic and neuroprotective molecules in the complex fighting against the degenerative diseases. The aim of this work was to evaluate the composition in punicalagins and ellagic acid of differently obtained extracts from whole fruit, peels and juices, prepared by squeezing or by centrifugation, of pomegranate belonging to different cultivars. Moreover, a wider phenolic fingerprint was also determined. The bioactivity of the extracts was tested on the redox activity of PDIA3 disulfide isomerase, an enzyme involved in the regulation of several cellular functions and associated with different diseases such as cancer, prion disorders, Alzheimer’s and Parkinson’s diseases. The results demonstrate that the different ratios between punicalagin and ellagic acid modulate the enzyme activity and other ellagitannins could interfere with this activity. Full article

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. Full article

Fruit and vegetable intake has been associated with a reduced risk of cardiovascular disease. Quercetin and kaempferol are among the most ubiquitous polyphenols in fruit and vegetables. Most of the quercetin and kaempferol in plants is attached to sugar moieties rather than in the free form. The types and attachments of sugars impact bioavailability, and thus bioactivity. This article aims to review the current literature on the bioavailability of quercetin and kaempferol from food sources and evaluate the potential cardiovascular effects in humans. Foods with the highest concentrations of quercetin and kaempferol in plants are not necessarily the most bioavailable sources. Glucoside conjugates which are found in onions appear to have the highest bioavailability in humans. The absorbed quercetin and kaempferol are rapidly metabolized in the liver and circulate as methyl, glucuronide, and sulfate metabolites. These metabolites can be measured in the blood and urine to assess bioactivity in human trials. The optimal effective dose of quercetin reported to have beneficial effect of lowering blood pressure and inflammation is 500 mg of the aglycone form. Few clinical studies have examined the potential cardiovascular effects of high intakes of quercetin- and kaempferol-rich plants. However, it is possible that a lower dosage from plant sources could be effective due to of its higher bioavailability compared to the aglycone form. Studies are needed to evaluate the potential cardiovascular benefits of plants rich in quercetin and kaempferol glycoside conjugates. Full article

Epidemiological data suggest that regular intake of isoflavones from soy reduces the incidence of estrogen-dependent and aging-associated disorders, such as menopause symptoms in women, osteoporosis, cardiovascular diseases and cancer. Equol, produced from daidzein, is the isoflavone-derived metabolite with the greatest estrogenic and antioxidant activity. Consequently, equol has been endorsed as having many beneficial effects on human health. The conversion of daidzein into equol takes place in the intestine via the action of reductase enzymes belonging to incompletely characterized members of the gut microbiota. While all animal species analyzed so far produce equol, only between one third and one half of human subjects (depending on the community) are able to do so, ostensibly those that harbor equol-producing microbes. Conceivably, these subjects might be the only ones who can fully benefit from soy or isoflavone consumption. This review summarizes current knowledge on the microorganisms involved in, the genetic background to, and the biochemical pathways of, equol biosynthesis. It also outlines the results of recent clinical trials and meta-analyses on the effects of equol on different areas of human health and discusses briefly its presumptive mode of action. Full article

Different diseases and disorders that affect the kidneys include, but are not limited to, glomerulonephritis, diabetic nephropathy, polycystic kidney disease, kidney stones, renal fibrosis, sepsis, and renal cell carcinoma. Kidney disease tends to develop over many years, making it difficult to identify until much later when kidney function is severely impaired and undergoing kidney failure. Although conservative care, symptom management, medication, dialysis, transplantation, and aggressive renal cancer therapy are some of the current strategies/approaches to kidney disease treatment, new preventative targeted therapies are needed. Epidemiological studies have suggested that a diet rich in fruits and vegetables is associated with health benefits including protection against kidney disease and renal cancer. Resveratrol, a polyphenol found in grapes and berries, has been reported to have antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, and anti-cancer properties. The current review summarizes the existing in vitro and in vivo animal and human studies examining the nephroprotective effects of resveratrol. Full article

Glutathione and aged garlic extract are sulfur-containing products that play important protective and regulatory roles within the immune system and in oxidative processes. Hydrogen sulfide (H₂S), an endogenous, gaseous, signaling transmitter, has also been shown to be involved in the regulation of inflammation. Recent studies have shown that sulfur-containing compounds from garlic have beneficial effects in attenuating outcomes associated with cardiovascular disease and inflammation by a mechanism that may be related to the H₂S signaling pathway. In this review, we summarize the main functions of glutathione (GSH), garlic derivatives and H₂S and their role in the immune response and impact on health and disease. Full article