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Abnormal glycerophospholipid (GPL) metabolism represented by phosphatidylcholine (PC) and phosphatidylethanolamine (PE) has been as a universal metabolic hallmark of cancer, which is involved in tumor progression. Our previous finding showed that peroxidase from foxtail millet bran (FMBP) exhibited significant anticolorectal cancer (CRC) activity in vitro and in nude mice. Presently, the potential of FMBP in clinical application was further evaluated by an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated carcinogenesis (CAC) mice model, revealed the pivotal role of GPL metabolism in anti-CRC effects of FMBP. Excitedly, FMBP significantly reduced the number and volume of CAC polyps of mice and effectively improved physiological indexes of CAC mice. Meanwhile, the elevated expressions of CRC early markers (cyclooxygenase 2, tumor-proliferating nuclear antigen Ki-67, and EGF module-containing mucin-like receptor 1) in CAC mice were efficiently prevented by FMBP treatment. Metabolomics analysis showed that the elevated abundances of PC and PE involved in GPL metabolism in CAC mice were markedly decreased in FMBP-treated groups, which was also verified in human CRC cells. Further, FMBP reduced the expression levels of PE and PC key metabolic enzymes, resulting in the blockage of GPL metabolism and insufficient adenosine triphosphate to maintain CRC growth. Collectively, FMBP has the potential as a preventive and therapeutic candidate for CRC through the blockage of GPL metabolism.

Purple sweet potato is known as a rich source of protein and anthocyanins. Anthocyanins can form complexes with protein present in food products through non-covalent forces or covalent bonds during processing, transportation, and storage as their protein affinity. We evaluated the hypoglycemic effects of protein-bound anthocyanin compounds of purple sweet potato (p-BAC-PSP) and free anthocyanin compounds of purple sweet potato (FAC-PSP) in high-fat diet/streptozotocin-induced diabetic mice. The results showed that administration of both p-BAC-PSP and FAC-PSP improved diabetic condition, as evidenced by the improvement of glucose tolerance and lipid metabolism, and the decrease of oxidative stress and liver damage. For the mechanism study, we have found that p-BAC-PSP and FAC-PSP induced the expression of AMP-activated protein kinase in liver. With p-BAC-PSP or FAC-PSP treatment, glucose transporter type 2, the protein levels of glucokinase, and insulin receptor α were found to be improved significantly ( p < 0.05). Glycolysis key genes, phosphofructokinase and pyruvate kinase, were upregulated in two treatment groups, while gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, were downregulated. Our findings suggested that p-BAC-PSP has great potential as a dietary supplement with hypoglycemic activity for general, pre-diabetic, and diabetic population.

Atherosclerosis is one of the main causes of cardiovascular diseases. Our previous study indicated that a type of peroxidase derived from foxtail millet bran (FMBP) had prominent antitumor activities. In the present study, we found that FMBP had potential antiatherosclerosis effects. The results showed that FMBP treatment strongly suppressed lipid phagocytosis in both HASMCs and THP-1 cells by 52% and 49%, respectively. Further, FMBP significantly inhibited HASMCs migration by promoting transformation of HASMCs from synthetic to contractile, leading to the decrease of lipid phagocytosis. Simultaneously, FMBP repressed lipid uptake by reducing the expression of CD36 in THP-1 cells. In addition, FMBP reduced the secretion of inflammatory factor IL-1β by inhibiting the expression of STAT3 in THP-1 cells. Interestingly, FMBP also had the same effects in models of atherosclerosis constructed with ApoE-/- mice, including decreased aortic lesion area, repressed aortic sinus CD36 and STAT3 expression, and elevated serum HDL-C concentration. Collectively, these results indicate that FMBP has great potential in preventing the development of atherosclerosis.

Dioscorins, the major storage proteins of yam tubers, exert immunomodulatory activities. To improve oral bioavailability of dioscorins in the intestine, recombinant dioscorin (rDioscorin) was coated with N,N,N-trimethyl chitosan (TMC) and tripolyphosphate (TPP), resulting in the formation of TMC-rDio-TPP nanoparticles (NPs). The loading capacity and entrapment efficiency of rDioscorin in the NPs were 26 ± 0.7% and 61 ± 1.4%, respectively. The NPs demonstrated a substantial release profile in the pH environment of the jejunum. The rDioscorin released from the NPs stimulated proliferation and phagocytosis of the macrophage RAW264.7 and activated the gene expression of IL-1β and IL-6. Incubation of the NPs in the Caco-2 cell monolayer led to a 5.2-fold increase of P app compared with rDioscorin alone, suggesting that rDioscorin, with the assistance of TMC, can be promptly transported across the intestinal epithelia. These results demonstrate that the TMC-rDio-TPP NPs can be utilized for elucidating the immunopharmacological effects of dioscorins through oral delivery.

The C57BL/6J mice were fed a 135-day normal diet or a high-fat diet (HFD) without, or concurrent with, a single yam dioscorin (80 mg/kg) or dipeptide NW (40 mg/kg) intervention every day. The final body weights (g) of mice were 26.1 ± 1.4, 34.97 ± 2.1, 31.75 ± 2.6, and 31.66 ± 3.1, respectively, for normal diet-fed, HFD-fed, dioscorin-intervened, and NW-intervened group. The mice in both intervened groups showed similar less weight gains and had significant differences (P < 0.05) compared to those in the HFD group under the same cumulative HFD intakes. The blood biochemical index of mice with dioscorin interventions showed significantly lower contents in total cholesterol and low-density lipoprotein, and NW interventions showed significantly lower total triglyceride contents compared to those of the HFD group (P < 0.05). Both intervened mice exhibited similar reductions in total visceral lipid contents and have significant differences compared to those of the HFD group (P < 0.05). The dioscorin intervention was better than NW interventions in lowering blood glucose levels by oral glucose tolerance tests and both showed significant differences (P < 0.05) compared to those in the HFD group. Yam dioscorin or dipeptide NW will potentially be used for preventive functional foods of less body weight gains and impaired glucose tolerance controls, which require further clinical trial investigations.

Momordica charantia is a commonly used food and has been used for the management of diabetes. Our previous study has identified an insulin receptor (IR)-binding protein (mcIRBP) from Momordica charantia. Here we identified the gastro-resistant hypoglycemic bioactive peptides from protease-digested mcIRBP. By in vitro digestion and IR kinase activity assay, we found that a 9-amino-acid-residue peptide, mcIRBP-9, was a gastro-resistant peptide that enhanced IR kinase activities. mcIRBP-9 activated IR signaling transduction pathway, which resulted in the phosphorylation of IR, the translocation of glucose transporter 4, and the uptake of glucose in cells. Intraperitoneal and oral administration of mcIRBP-9 stimulated the glucose clearance by 30.91 ± 0.39% and 32.09 ± 0.38%, respectively, in streptozotocin-induced diabetic mice. Moreover, a pilot study showed that daily ingestion of mcIRBP-9 for 30 days decreased the fasting blood glucose levels and glycated hemoglobin (HbA1c) levels by 23.62 ± 6.14% and 24.06 ± 1.53%, respectively. In conclusion, mcIRBP-9 is a unique gastro-resistant bioactive peptide generated after the digestion of mcIRBP. Furthermore, oral administration of mcIRBP-9 improves both the glucose tolerance and the HbA1c levels in diabetic mice via targeting IR signaling transduction pathway.

Bioactive peptides derived from foods have shown beneficial anti-inflammatory potential. Inhibitory κB kinase-β (IKKβ) plays a crucial role in the activation of nuclear factor-κB (NF-κB), a transcription factor involved in inflammation. Here we applied proteomic and bioinformatics approaches to identify anti-inflammatory peptides that target IKKβ from corn silk. Corn silk extract significantly suppressed lipopolysaccharide (LPS)-induced NF-κB activities [(1.7 ± 0.2)-fold vs (3.0 ± 0.6)-fold, p < 0.05] in cells. Trypsin hydrolysate of corn silk also suppressed LPS-induced NF-κB activities [(1.1 ± 0.3)-fold vs 3.3 ± 0.5 fold, p < 0.01]. In addition, both corn silk extract and trypsin hydrolysate significantly inhibited LPS-induced interleukin-1β (IL-1β) production by 58.3 ± 4.5 and 55.1 ± 7.4%, respectively. A novel peptide, FK2, docked into the ATP-binding pocket of IKKβ, was further identified from trypsin hydrolysis of corn silk. FK2 inhibited IKKβ activities, IκB phosphorylation, and subsequent NF-κB activation [(2.3 ± 0.4)-fold vs (5.5 ± 0.4)-fold, p < 0.001]. Moreover, FK2 significantly reduced NF-κB-driven luminescent signals in organs by 5-11-fold and suppressed LPS-induced NF-κB activities and IL-β production in tissues. In conclusion, our findings indicated that corn silk displayed anti-inflammatory abilities. In addition, we first identified an anti-inflammatory peptide FK2 from corn silk. Moreover, the anti-inflammatory effect of FK2 might be through IKKβ-NF-κB signaling pathways.

Peanut allergy is an IgE-mediated hypersensitivity. Upon peanut consumption by an allergic individual, epitopes on peanut proteins bind and cross-link peanut-specific IgE on mast cell and basophil surfaces triggering the cells to release inflammatory mediators responsible for allergic reactions. Polyphenolic phytochemicals have high affinity to bind proteins and form soluble and insoluble complexes with unique functionality. This study investigated the allergenicity of polyphenol-fortified peanut matrices prepared by complexing various polyphenol-rich plant juices and extracts with peanut flour. Polyphenol-fortified peanut matrices reduced IgE binding to one or more peanut allergens (Ara h 1, Ara h 2, Ara h 3, and Ara h 6). Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) suggested changes in secondary protein structure. Peanut protein-cranberry polyphenol fortified matrices triggered significantly less basophil degranulation than unmodified flour in an ex vivo assay using human blood and less mast cell degranulation when used to orally challenge peanut-allergic mice. Polyphenol fortification of peanut flour resulted in a hypoallergenic matrix with reduced IgE binding and degranulation capacity, likely due to changes in protein secondary structure or masking of epitopes, suggesting potential applications for oral immunotherapy.

Buckwheat (Fagopyrum esculentum) is rich in antihypertensive compounds. This study investigated the effect of lactic-fermented buckwheat sprouts (neo-FBS) on level, identification, and potency of blood pressure-lowering (BPL) compounds. A single oral dose of 1.0 mg/kg body weight buckwheat sprouts (BS) in spontaneously hypertensive rats did not show significant BPL activity, whereas neo-FBS significantly decreased blood pressure. HPLC of neo-FBS identified two peaks absent in the profile of BS. The peak exhibiting potent BPL activity was fractionated, and six peptides (DVWY, FDART, FQ, VAE, VVG, and WTFR) and tyrosine were identified by LC-MS/MS and Edman degradation. Single oral dose administration of the peptides revealed significant BPL effect of all the peptides, with the most potent being DVWY, FQ, and VVG. DVWY, VAE, and WTFR are novel. This study demonstrates that lactic fermentation of BS produces new, highly potent antihypertensive peptides and increases active compounds GABA and tyrosine already present in BS.

Wheat (Triticum spp. L.), rye (Secale cereal L.), and barley (Hordeum vulgare L.) seeds contain peptides toxic to celiac patients. Maize (Zea mays L.) and rice (Oryza sativa L.) are distant relatives of wheat as well as sorghum (Sorghum bicolor (L.) Moench) and are known to be safe for celiacs. Both immunochemical studies and in vitro and in vivo challenge of wheat-free sorghum food products support this conclusion, although molecular evidence is missing. The goal of the present study was to provide biochemical and genetic evidence that sorghum is safe for celiac patients. In silico analysis of the recently published sorghum genome predicts that sorghum does not contain peptides that are toxic for celiac patients. Aqueous/alcohol-soluble prolamins (kafirins) from different sorghum varieties, including pure lines and hybrids, were evaluated by SDS-PAGE and HPLC analyses as well as an established enzyme-linked immunosorbent assay (ELISA) based on the R5 antibody. These analyses provide molecular evidence for the absence of toxic gliadin-like peptides in sorghum, confirming that sorghum can be definitively considered safe for consumption by people with celiac disease.

The physiological effects of the hydrolysates of white rice protein (WRP), brown rice protein (BRP), and soy protein (SP) hydrolyzed by the food grade enzyme, alcalase2.4 L, were compared to the original protein source. Male Syrian Golden hamsters were fed high-fat diets containing either 20% casein (control) or 20% extracted proteins or their hydrolysates as the protein source for 3 weeks. The brown rice protein hydrolysate (BRPH) diet group reduced weight gain 76% compared with the control. Animals fed the BRPH supplemented diet also had lower final body weight, liver weight, very low density lipoprotein cholesterol (VLDL-C), and liver cholesterol, and higher fecal fat and bile acid excretion than the control. Expression levels of hepatic genes for lipid oxidation, PPARα, ACOX1, and CPT1, were highest for hamsters fed the BRPH supplemented diet. Expression of CYP7A1, the gene regulating bile acid synthesis, was higher in all test groups. Expression of CYP51, a gene coding for an enzyme involved in cholesterol synthesis, was highest in the BRPH diet group. The results suggest that BRPH includes unique peptides that reduce weight gain and hepatic cholesterol synthesis.

An arabinogalactan-protein (WSSP-AGP) was isolated from the tuberous cortex of the white-skinned sweet potato (WSSP; Ipomoea batatas L.). It consists of 95% (w/w) carbohydrate and 5% (w/w) protein with high contents of hydroxyproline, alanine, and serine. Its sugar composition is α-L-Rha:α-L-Ara:β-D-Gal:β-D-GlcA in a molar ratio of 1.0:4.1:7.6:1.3. Its weight-average molecular weight was estimated to be 126,800 g/mol by high-performance size exclusion chromatography coupled with multiangle laser light scattering. Structural analysis indicated that WSSP-AGP is a (1→3)-β-D-galactan highly branched at O-6 with (1→6)-β-D-galactan, in which the branched chains are substituted at the O-3 position with α-L-Araf-(1→ and α-L-Araf-(1→5)-α-L-Araf-(1→ and at the O-6 position typically with α-L-Rhap-(1→4)-β-D-GlcAp-(1→ as terminating groups. Continuous administration of WSSP-AGP to KKAy mice significantly lowered fasting plasma glucose levels. This indicates that WSSP-AGP plays an important role in the hypoglycemic effects of WSSP.

A novel pea protein-based emulsifier was used in the production of oil in water (O/W) nanoemulsions. The regions of kinetically stabilized O/W emulsions were individuated in a pseudoternary diagram containing different pea protein, sunflower oil, and water fractions. The stable O/W emulsion region was widened by the addition of NaCl to the aqueous phase or, to a more significant extent, by high pressure homogenization (HPH) processing. The HPH treatment caused the formation of very fine emulsions in the nanometric range (<200 nm), with extremely high stability over time. HPH treatment affected the protein properties, resulting in a reduced water surface tension. Changes in protein structure, which were characterized by light scattering and SDS-PAGE, suggest the occurrence of the disruption of disulfide bonds, thus changing the exposition and availability of hydrophobic groups.

Dioscorin, the tuber storage protein of yam, was reported to have immunomodulatory activity in RAW264.7 murine macrophage cell lines ( Food and Chemical Toxicology , 2007 , 45 , 2312 -2318 ). However, the immunomodulatory function of dioscorin after being ingested was not elucidated in vivo. Hence, BALB/c mice were given oral dioscorin (2.5 and 20 mg/kg/day) once a day for 21-days. Lymphocyte subpopulation changes in the peripheral blood and splenocytes, stimulation in phagocytosis of the polymorphonuclear cell (PMN) and monocytes, the natural killer (NK) cell cytotoxicity, the splenocyte proliferation, and cytokine secretions in the presence of PHA were determined. The number changes of Peyer's patches and secreted IgA (sIgA) in the feces were determined. Oral dioscorin for 21-days increased the subpopulation in natural killer cells (CD49(+)) and/or B cells (CD19(+)), elevated the phagocytosis of PMN (p < 0.01) and MON (p < 0.01), and the NK cell cytotoxic activity (p < 0.05), and stimulated splenocyte proliferations in the presence of LPS or PHA (p < 0.05) in comparison with those of the control. Cytokines of INF-gamma, IL-4, and IL-10 secretions, the numbers of Peyer's patches, and sIgA in the feces showed higher levels in oral dioscorin and significant difference to those of the control (p < 0.001). These results suggested that dioscorin exhibited systemic and mucosal immunomodulatory activities after being ingested in vivo.

A study of repeated oral administration of transgenic rice containing a hybrid peptide of major human T-cell epitopes (7Crp) from Japanese cedar pollen allergens was carried out in cynomolgus macaques over 26 weeks. The monkeys were divided into three groups, each comprising three males and three females, administered a high dose of transgenic rice, a low dose of transgenic rice, or a high dose of the parental rice strain. The transgenic rice 7crp#10 and the parental nontransgenic control were polished, steamed, mashed, and prepared in water at 40% (w/v). Monkeys were orally administered a high or low dose of transgenic rice or the nontransgenic control by gavage every day. No adverse effects on general behavior or body weight of animals were observed during the study. Analysis of blood from monkeys administered for 26 weeks showed that, with few exceptions, there were no significant differences in hematological or biochemical values between them. Additionally, neither pathological symptoms nor histopathological abnormalities were observed. Thus, it was concluded that oral administration of transgenic rice containing T-cell epitopes from Japanese cedar pollen allergens has no adverse effects.

The aim of this study was to elucidate the effect of the major storage protein dioscorin isolated from two different yam species, Tainong No. 1 (TN1-dioscorins) and Japanese yam (Dj-dioscorins), on the immune activities of mice. Dj-dioscorins, like TN1-dioscorins, could induce expression of the pro-inflammatory cytokines and stimulate phagocytosis of RAW 264.7. Intraperitoneal injection of the TN1-dioscorins into mice stimulated phagocytosis of bone marrow, spleen, and thymic cells. In contrast, the T and B cells in bone marrow, spleen, and thymus isolated from mice injected with Dj-dioscorins had higher proliferative responses to mitogens. Furthermore, Dj-dioscorins enhanced proliferation of CD4(+), CD8(+), and Tim3(+) (Th1) cells in spleen and CD19(+) cells in both spleen and thymus. Supplement of Dj-dioscorins in the lymphoid cells isolated from Dj-dioscorins primed mice induced cell proliferation of both spleen and thymic cells. These findings indicated that TN1-dioscorins have a higher ability to stimulate the phagocytic activity of the lymphoid cells than Dj-dioscorins, whereas Dj-dioscorins possess more abilities than TN1-dioscorins to enhance the proliferation of the lymphoid cells.

Suppression of postprandial hyperglycemia reduces lipogenic enzyme activities in the adipose tissues of normal rats. The present study investigated the expression of genes related to lipogenesis and insulin sensitivity in mesenteric adipose and epididymal adipose tissues to evaluate the effects of wheat albumin (WA) and a crude preparation of WA (CWA) with alpha-amylase inhibitory activity on lipid metabolism. Rats fed 2.5% WA, which had 12.7-fold inhibitory activity compared with CWA, exhibited reduced mRNA levels for G6PDH, ACO, ACS, PEPCK, and LPL in the mesenteric adipose, but not in the epididymal adipose tissue. Linear regression analyses showed that the gene expression levels of FAS, G6PDH, ACS, and LPL were reduced in dose-dependent manners in the mesenteric adipose tissue of rats fed the CWA diet. These results suggest that supplementation with CWA as well as WA reduces the expression of genes related to lipogenesis and insulin sensitivity in mesenteric adipose tissue.

The aim of this study was to isolate the protein fractions from chickpea, var. IAC-Marrocos, as well as to evaluate its in vivo nutritional protein quality. Among the proteins, albumins showed better nutritional value in the in vivo assays and amino acid contents, despite their higher trypsin inhibitor contents. Trypsin inhibitors were found to be heat labile in all samples, but the digestibility results for unheated and heated flour and albumins suggest that their contents are not very decisive. The PER values for casein (not supplemented) were very similar to those of heated flour and unheated or heated albumin and total globulins. The albumin and glutelin fractions showed the best results for PDCAAS, however, lower than those of casein. Despite the high digestibility of the globulin the very low essential amino acid content lowered its PDCAAS, and it had the lowest values.

Okara (a byproduct of the soy milk industry) is rich in proteins (24.5-37.5 g/100 g of dry matter (dm)), lipids (9.3-22.3 g/100 g of dm), and dietary fiber (DF) (14.5-55.4 g/100 g of dm). It also contains isoflavones (0.14 g/100 g of dm). In the present study we fed female healthy Wistar rats either a standard rat diet or a supplemented 10% DF-rich okara (DFRO) diet for 4 weeks, and then we assessed several health parameters in the serum and the cecum compartments. In comparison to the control group, rats fed DFRO showed a significant decrease in weight gain (5.00 +/- 1.22 g vs 2.00 +/- 1.46 g, P < 0.03, during week 4) and in total cholesterol (65 +/- 8 mg/dL vs 51 +/- 5 mg/dL, P < 0.05) and a significantly increased antioxidant status (36.71 +/- 15.31 micromol of Trolox equivalents (TEs)/g vs 69.75 +/- 16.11 micromol of TEs/g, P < 0.0003) and butyrogenic effect (39.37%, P < 0.003) in the cecum. In addition, a significant enhancement in the apparent absorption (41.89 +/- 1.64% vs 47.02 +/- 2.51%, P < 0.004) and in the true retention (41.62 +/- 1.60% vs 46.68 +/- 2.55%, P < 0.005) of calcium was appreciated. In summary, these findings show for the first time that a concentrate DF from a soybean byproduct protects the gut environment in terms of antioxidant status and prebiotic effect. These results may highlight the development of an innovative soybean byproduct rich in DF which could be useful as a functional ingredient with health-promoting attributes.

The effects of concentrated carrot protein (CCP) containing 15.4% (w/w) carrot (Daucus carota) antifreeze protein on texture properties of frozen dough and volatile compounds of crumb were studied. CCP supplementation lowered the freezable water content of the dough, resulting in some beneficial effects including holding loaf volume steadily and making the dough softer and steadier during frozen storage. Furthermore, SPME-GC-MS analysis showed CCP supplementation did not give any negative influences on volatile compounds of crumb and gave a pleasant aroma felt like Michelia alba DC from trans-caryophyllene simultaneously. Combining our previous results that CCP supplementation improves the fermentation capacity of the frozen dough, CCP could be used as a beneficial additive for frozen dough processing.

A calcium-soluble protein isolate (CSPI) was prepared from the supernatant obtained after addition of 0.75 M calcium chloride to a pH 5.0 aqueous extract of yellow mustard (Sinapis alba) seed meal. Total amino acid analysis showed that the CSPI has significantly higher (p < 0.05) contents of glutamic acid + glutamine, cysteine, and proline when compared to the precipitated, calcium-insoluble proteins. Peptide mass fingerprinting of tryptic peptides of the major polypeptides by mass spectrometry indicated that the CSPI is composed mainly of cruciferin proteins with a contribution from napins (the major allergenic proteins of S. alba). The S. alba CSPI had significantly higher (p < 0.05) protein solubility and emulsion formation ability in the presence of 0.75 M calcium chloride when compared to similar isolates prepared from Brassica juncea (brown mustard) and soybean seed meals. We suggest that the S. alba CSPI could be used to prepare calcium-fortified high protein liquid products. However, the presence of allergenic proteins in this extract may limit its widespread food use.

The nutritional and physiological effects of raw cowpea (Vigna unguiculata (L) Walp.) seed meal, protein isolate (globulins), or starch on the metabolism of young growing rats have been evaluated in 14-day trials. Wet and dry weight gain, feed conversion efficiency, and lipid and protein accretion were significantly reduced as a result of inclusion of seed meal, globulins, or starch in the diet, with growth retardation being most marked with the seed meal. The proportional weights of the small intestine and pancreas were increased by meal diets, and serum cholesterol levels were slightly reduced. The globulins and raw starch also increased relative small intestine weights but had no effect on the pancreas or serum constituents. The effects of cowpeas on rats appeared to be due primarily to the combined actions of globulins, resistant starches, protease inhibitors, and possibly fiber and non-starch polysaccharides on intestinal and systemic metabolism.