Formation of Hesperetin-Methylglyoxal Adducts in Food and In Vivo, and Their Metabolism In Vivo and Potential Health Impacts.

Polyphenols with a typical meta-phenol structure have been intensively investigated for scavenging of methylglyoxal (MGO) to reduce harmful substances in food. However, less attention has been paid to the formation level of polyphenol-MGO adducts in foods and in vivo and their absorption, metabolism, and health impacts. In this study, hesperitin (HPT) was found to scavenge MGO by forming two adducts, namely, 8-(1-hydroxyacetone)-hesperetin (HPT-mono-MGO) and 6-(1-hydroxyacetone)-8-(1-hydroxyacetone)-hesperetin (HPT-di-MGO). These two adducts were detected (1.6-15.9 mg/kg in total) in cookies incorporated with 0.01%-0.5% HPT. HPT-di-MGO was the main adduct detected in rat plasma after HPT consumption. The adducts were absorbed 8-30 times faster than HPT, and they underwent glucuronidation and sulfation in vivo. HPT-mono-MGO would continue to react with endogenous MGO in vivo to produce HPT-di-MGO, which effectively reduced the cytotoxicity of HPT and HPT-mono-MGO. This study provided data on the safety of employing HPT as a dietary supplement to scavenge MGO in foods.

Esterification of black bean anthocyanins with unsaturated oleic acid, and application characteristics of the product.

Esterification of anthocyanins with saturated fatty acids have been widely investigated, while that with unsaturated fatty acids is little understood. In this study, crude extract (purity âˆ¼ 35 %) of cyanidin-3-O-glucoside (C3G) from black bean seed coat was utilized as reaction substrate, and enzymatically acylated with unsaturated fatty acid (oleic acid). Optimization of various reaction parameters finally resulted in the highest acylation rate of 54.3 %. HPLC-MS/MS and NMR analyses elucidated the structure of cyanidin-3-O-glucoside-oleic acid ester (C3G-OA) to be cyanidin-3-O-(6″-octadecene)-glucoside. Introduction of oleic acid into C3G improved the lipophilicity, antioxidant ability, and antibacterial activity. Further, the color and substance stability analyses showed that the susceptibility of C3G and C3G-OA to different thermal, peroxidative, and illuminant treatments were highly pH dependent, which suggested individual application guidelines. Moreover, C3G-OA showed lower toxicity to normal cell (QSG-7701) and better inhibitory effect on the proliferation of HepG2 cells than C3G, which indicated its potential anti-tumor bioactivity.

Glyoxal in Foods: Formation, Metabolism, Health Hazards, and Its Control Strategies.

Glyoxal is a highly reactive aldehyde widely present in common diet and environment and inevitably generated through various metabolic pathways in vivo. Glyoxal is easily produced in diets high in carbohydrates and fats via the Maillard reaction, carbohydrate autoxidation, and lipid peroxidation, etc. This leads to dietary intake being a major source of exogenous exposure. Exposure to glyoxal has been positively associated with a number of metabolic diseases, such as diabetes mellitus, atherosclerosis, and Alzheimer's disease. It has been demonstrated that polyphenols, probiotics, hydrocolloids, and amino acids can reduce the content of glyoxal in foods via different mechanisms, thus reducing the risk of exogenous exposure to glyoxal and alleviating carbonyl stresses in the human body. This review discussed the formation and metabolism of glyoxal, its health hazards, and the strategies to reduce such health hazards. Future investigation of glyoxal from different perspectives is also discussed.

Cytotoxicity of a Novel Compound Produced in Foods via the Reaction of Amino Acids with Acrolein along with Formaldehyde.

Acrolein (ACR) and formaldehyde (FA) are toxic aldehydes co-produced in foods. This work found that amino acids, the nucleophiles ubiquitously existing in foods, can react simultaneously with them. Six amino acids, including γ-aminobutyric acid (GABA), glycine, alanine, serine, threonine, and glutamine, can scavenge ACR and FA at 37, 85, and 160 °C. GABA had the highest scavenging capacity for ACR and FA, by 79 and 13% at 37 °C for 2 h, and 99 and 48% at 160 °C for 30 min, respectively. Moreover, a new type of compound with a basic structure of 5-formyl-3-methylene-3,6-dihydropyridin was identified in all reactions and formed by 1 molecule of FA and amino acid and 2 molecules of ACR. The content of this compound was higher than that of free ACR in typical thermally processed foods. Moreover, the compounds produced from different amino acids showed different cytotoxicity values. In gastric epithelial and human intestinal epithelial cell lines, the cytotoxicity values of serine-sourced and threonine-sourced products were lower than that of ACR but higher than that of FA, whereas others had less toxicity compared with the two aldehydes. Considering that the content of serine-sourced products was the highest in almost all tested foods, their safety needs to be evaluated.

Rutin alleviated acrolein-induced cytotoxicity in Caco-2 and GES-1 cells by forming a cyclic hemiacetal product.

Acrolein (ACR), an α, ß-unsaturated aldehyde, is a toxic compound formed during food processing, and the use of phenolics derived from dietary materials to scavenge ACR is a hot spot. In this study, rutin, a polyphenol widely present in various dietary materials, was used to investigate its capacity to scavenge ACR. It was shown that more than 98% of ACR was eliminated under the conditions of reaction time of 2 h, temperature of 80 °C, and molar ratio of rutin/ACR of 2/1. Further structural characterization of the formed adduct revealed that the adduct of rutin to ACR to form a cyclic hemiacetal compound (RAC) was the main scavenging mechanism. Besides, the stability of RAC during simulated in vitro digestion was evaluated, which showed that more than 83.61% of RAC was remained. Furthermore, the cytotoxicity of RAC against Caco-2 and GES-1 cells was significantly reduced compared with ACR, where the IC50 values of ACR were both below 20 µM while that of RAC were both above 140 µM. And the improvement of the loss of mitochondrial membrane potential (MMP) by RAC might be one of the detoxification pathways. The present study indicated that rutin was one of the potential ACR scavengers among natural polyphenols.

Water-In-Oil Pickering Emulsions Stabilized by Microcrystalline Phytosterols in Oil: Fabrication Mechanism and Application as a Salt Release System.

Recently, Pickering emulsions stabilized by edible particles have attracted significant attention from the scientific community and food industry owing to their surfactant-free character. However, those edible particles are mostly used for stabilizing oil-in-water emulsions, whereas those for water-in-oil emulsions are very limited. In this article, stable water-in-oil Pickering emulsions were prepared through dispersing phytosterol particles in oil phase, and the effects of antisolvent treatment, the type of oil, particle concentration, and water fraction on the stability, type, and morphology of these emulsions were investigated. In addition, the release profile of salt as a model aqueous compound from these emulsions has also been studied. Results showed that due to its higher water content, the antisolvent pretreatment of phytosterol in the ethanol/water system facilitated the dispersion of dried phytosterol particles into oil phase as microcrystals. Water-in-oil Pickering emulsions with droplet sizes of 80-100 µm were fabricated at phytosterol concentrations of 1.5-3% w/v and water fractions of 0.2-0.6. The dissolved phytosterol molecules in oil phase could help in emulsion stabilization through interfacial crystallization during emulsification, evidenced by polar microscopic observations. Moreover, the salt release from phytosterol-stabilized Pickering emulsions showed a temperature-dependent profile which could have potential application in a controlled-release system. The current study provided important information for fabrication of stable water-in-oil emulsion using natural particles.

Glycine and serine markedly eliminate methylglyoxal in the presence of formaldehyde via the formation of imidazole salts.

l-glycine and l-serine are the building blocks of proteins and exhibit various biological activities. This work found that l-glycine and l-serine show low scavenging capacity for methylglyoxal at moderate conditions (pH 7.0, 37 °C). However, they efficiently eliminate methylglyoxal and formaldehyde when the two aldehydes co-exist, via generation of imidazole salt, a compound formed by one molecule of methylglyoxal and formaldehyde, and two molecules of amino acids. The imidazole salts were identified in biscuits and fried potato crisps. Moreover, the formation of imidazole salts greatly decreased the cytotoxicity of their precursors, methylglyoxal and formaldehydes. This finding suggests that glycine and serine can be used to scavenge these two harmful aldehydes both after intake and during food processing.

Cytotoxicity of adducts formed between quercetin and methylglyoxal in PC-12 cells.

Quercetin (Que) or quercetin-containing food stuffs are widely incorporated in bakery foods for improving food texture and health effects, and scavenging reactive aldehydes, such as methylglyoxal (MGO) that exhibits various deleterious effects including contribution to neurodegeneration. This study aimed to investigate the cytotoxicity of the adducts formed between quercetin and MGO resulted from the incorporation of quercetin in foods. Two highly-purified adducts (Que-mono-MGO and Que-di-MGO) were found to display higher cytotoxicity than their precursor MGO and quercetin. They elevated apoptosis via upregulation of expression of apoptotic markers, including p-P38, cleaved caspase-9 and -3, and pro-apoptotic Bax. They induced mitochondrial dysfunction via decreasing mitochondrial membrane potential and increasing lactate dehydrogenase release. Moreover, they attenuated levels of p-Akt, Nrf2, NQO-1, and HO-1, proving that they induced neurodegeneration apoptosis through mitochondria-mediated signaling pathways (PI3K-Akt and Nrf2-HO-1/NQO-1). These findings indicated that the safety consequence of MGO after scavenged by polyphenols needs to be concerned.

Water-in-Oil Pickering Emulsions Stabilized Solely by Water-Dispersible Phytosterol Particles.

Water-in-oil (W/O) Pickering emulsions were successfully synthesized by water-dispersible phytosterol (PS) particles formed through simple antisolvent precipitation. The effects of the organic/aqueous ratio on the particle morphology, crystallinity, and contact angle were investigated. Sheet-like PS particles with reduced crystallinity were further used as W/O Pickering emulsion stabilizers. The properties of the formed W/O emulsions could be transformed by changing the oil type, water-phase fraction, or particle contents. Results showed that emulsions with 80% water fraction could be stabilized by 3% particles in the aqueous phase, where dodecane was used as the oil phase. W/O Pickering emulsions stabilized by PS particles showed temperature responsiveness. When dried, PS particles could be well dispersed either in the water or oil phase to stabilize W/O Pickering emulsions. Therefore, this kind of PS particles could not only enrich the family of food-grade Pickering stabilizers, especially the W/O type, but also provide a smart Pickering stabilizer to fabricate environmental-responsive emulsion products.

Formation and Identification of Two Hydroxmethylfurfural-Glycine Adducts and Their Cytotoxicity and Absorption in Caco-2 Cells.

Our previous research showed that thioacetal and Schiff base formed between 5-hydroxymethylfurfural (HMF) and cysteine or lysine considerably decreased the cytotoxicity of HMF. In this study, two adol condensation adducts, named 2ß-amino-3α-hydroxy-3-(5-(hydroxymethyl)furan-2-yl)propanoic acid (HGA) and 2α-amino-3ß-hydroxy-3-(5-(hydroxymethyl)furan-2-yl)propanoic acid (HGB), were prepared from the reaction products of glycine and HMF, and their cytotoxicities were investigated in Caco-2 cells. Compared with HMF, HGA and HGB displayed lower cytotoxicities against Caco-2 cells with IC50 values of 36.50 and 43.47 mM, respectively, versus 16.11 mM (HMF). In contrast to our findings in thioacetal and Schiff base products, HGA and HGB underwent a very high metabolism rate (99%) in Caco-2 cells. HGA and HGB may degrade to other products instead of HMF since no extracellular or intracellular HMF was detected.

Formation of di-cysteine acrolein adduct decreases cytotoxicity of acrolein by ROS alleviation and apoptosis intervention.

Acrolein (ACR) is a toxic contaminant for humans. Our previous research indicated that l-cysteine (Cys) decreased the cytotoxicity of acrolein possibly via adduct formation, but which adduct contributed to the toxicity-lowering effect remains unknown. In this work, we identified a di-cysteine acrolein adduct (ACR-di-Cys) and investigated its toxicity against human bronchial epithelial cell line HBE and colon cancer cell line Caco-2. ACR-di-Cys tremendously decreased acrolein-induced cytotoxicity via alleviating ROS and apoptosis intervention. In the condition of no presence of free cysteine, however, this adduct can convert to mono-ACR-Cys in PBS solution by losing a molecule of cysteine conjugated at CC bond. ACR-mono-Cys showed much higher toxicity than ACR-di-Cys, and even higher than acrolein after 48 h exposure. This study indicated that cysteine can react with acrolein to form adducts with different acrolein-detoxifying capacity, and a sufficient intake of cysteine or cysteine-containing proteins can maximize the detoxifying effect for acrolein via the formation of a highly detoxifying agent, ACR-di-Cys.

Alternating consumption of ß-glucan and quercetin reduces mortality in mice with colorectal cancer.

The current dietary recommendations for disease prevention and management are scarce and are not well supported. Beta-glucan or quercetin in a diet can alleviate colorectal cancer (CRC) by regulating the gut microbiota and related genes, but the effects of alternating their consumption for routine ingestion during CRC occurrence remain unknown. This study investigated the effects of alternating the consumption of ß-glucan and quercetin for routine ingestion on CRC development in mice. The mortality rate, colonic length, inflammatory cytokines, gut microbiota, and colonic epithelial gene expression in healthy and CRC mice that consumed normal and alternate diets were compared and studied. The results showed that alternating the consumption of ß-glucan and quercetin (alternating among a ß-glucan diet, a normal diet and a normal diet that was supplemented with quercetin) alleviated colon damage and reduced the mortality rate in CRC mice, with a reduction in mortality of 12.5%. Alternating the consumption of ß-glucan and quercetin significantly decreased the TNF-α level, increased the relative abundance of Parabacteroides, and downregulated three genes (Hmgcs2, Fabp2, and Gpt) that are associated with inflammation and cancer. Alternating the consumption of some bioactive compounds, such as ß-glucan and quercetin, in food can contribute to human health. This experiment provided some experimental evidence for the dietary recommendations for disease prevention and management.

Ganoderma lucidum polysaccharide improves rat DSS-induced colitis by altering cecal microbiota and gene expression of colonic epithelial cells.

BACKGROUND: The effects of ß-glucan on colitis mice are contradictory in previous reports. As a result, it is still unclear whether there is an anti-colitis effect in Ganoderma lucidum polysaccharide (GLP), which is mainly composed of ß-glucan. Moreover, the association between GLP function and gut microbiota remains to be elucidated. OBJECTIVE: This study aimed to investigate whether GLP consumption improved rat dextran sodium sulfate (DSS)-induced colitis by regulating gut microbiota and altering colonic epithelial expression. DESIGN: The disease activity index (DAI) scores and the cecal short chain fatty acid (SCFA) levels of DSS-induced colitis rats fed with a GLP diet (Group GLP, n = 6) and a control diet (Group Con, n = 6) were investigated and analyzed. Moreover, the profiles of gut microbiota and colonic epithelial expression were analyzed using metagenomics and transcriptomics. RESULTS: GLP consumption significantly lowered animal DAI scores by producing more SCFAs by increasing SCFA-producing bacteria such as Ruminococcus_1 and reducing pathogens such as Escherichia-Shigella in both the small intestine and cecum of rat. Moreover, GLP consumption regulated 11 genes, including six upregulated (Ccl5, Cd3e, Cd8a, Il21r, Lck, and Trbv) and five downregulated (Ccl3, Gro, Il11, Mhc2, and Ptgs) genes enriched in six inflammation-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, resulting in enhancement of immunity and reduction of inflammatory response and colonic cancer risk. CONCLUSIONS: GLP consumption alleviated DSS-induced colitis and may have potential for ulcerative colitis relief.

Influences of stir-frying and baking on flavonoid profile, antioxidant property, and hydroxymethylfurfural formation during preparation of blueberry-filled pastries.

Bakery products with fruit fillings are growing fast. Blueberry-filled pastries are widely consumed in China. This study aimed to investigate the effects of two thermal processing procedures (stir-frying and baking) on flavonoid profile, antioxidant property, and hydroxymethylfurfural (HMF) formation during preparation of blueberry-filled pastries. Stir-frying contributed the most to the variations in these values in blueberry filling. Anthocyanins (48%-53% reduction in total) were more susceptible to thermal processing than flavonols (11%-16%). Among anthocyanins, delphinidin glycosides (61%-67% reduction) were the most unstable, followed by malvidin (52%-58%), petunidin (40%-45%), and cyanidin (38%-41%). A high level of HMF (300 mg/kg) was formed during stir-frying. Except for anthocyanins, baking did not significantly influence HMF formation, flavonol degradation, and antioxidant property in the fillings. Stir-frying processing conditions rather than baking must be further investigated for nutrient retention and HMF inhibition.

The Alternate Consumption of Quercetin and Alliin in the Traditional Asian Diet Reshaped Microbiota and Altered Gene Expression of Colonic Epithelial Cells in Rats.

The diet of traditional Asian is similar to the Mediterranean that was considered as a healthy dietary pattern. The report was scarce on whether different plant-derived components with similar anti-oxidative and anti-inflammatory function such as quercetin and alliin in traditional Asian diet consumed in an alternate style cooperatively affect health including the growth of host and the status of the gut microbiota and colonic epithelial immunity. In the present study, the effects of alternate consumption of quercetin and alliin on host health judging by the profile of gut microbiota and gene expression of colonic epithelial cells were investigated with the Illumina MiSeq sequencing (16S rRNA genes) and Illumina HiSeq (RNA-seq) technique, respectively. The results showed that the alternate consumption significantly increased the rat body weight and reshaped the gut microbiota composition. At the phylum level, it significantly increased the relative abundance of fecal Firmicutes and Cyanobacteria but decreased that of Bacteroidetes (P < 0.05) and increased the relative abundance of Candidatus Arthromitus, Lactococcus, Geobacillus, and Ruminococcus at the genus level that benefits the host's health. The alternate consumption of quercetin and alliin also altered 13 genes expression involved in the KEGG pathways of complement and coagulation cascades and hematopoietic cell lineage to improve the gut immunity. Therefore, the alternate consumption of quercetin and alliin in traditional Asian diet can contribute beneficial metabolic effects by optimizing gut microbiota and altering the immunologic function of colonic epithelial cells, resulting in its potential to improve the sub-health status.

Positive and negative effects of polyphenol incorporation in baked foods.

Polyphenols are hot research topics worldwide owing to their physiological and pharmaceutical activities. Polyphenols and polyphenol-enriched by-products have been widely used in bakery foods because of their neutraceutical properties. This review summarizes the classification, biosynthesis, main source and analysis of polyphenols and intensively discusses the effects of their incorporation in baked foods. The positive effects of polyphenol incorporation include elevation of antioxidant activity of baked foods, scavenging of food-borne toxins produced during thermal processing and decreasing postprandial serum glucose level. Meanwhile, polyphenol incorporation negatively influences colour, texture and flavour of baked foods and bioavailability of the added polyphenols. Most polyphenols are thermally sensitive and reactive. Thus far, few studies have investigated on neoformed compounds from the reaction of polyphenols or their oxidised products (quinones) with other food components. Before launching polyphenol-incorporated bakery foods in the market, future work should focus on full toxicological evaluation of newly derived compounds from polyphenols.

Metabolism of anthocyanins and consequent effects on the gut microbiota.

Anthocyanins are natural water-soluble polyphenols present in fruits and vegetables. Health-promoting effects attributed to anthocyanins are mainly associated with oxidative stress inhibition and gut microbiota modulation. Dietary anthocyanins undergo a complex metabolism after ingestion and interact with endogenous and microbial enzymes, leading to the production of a large number of circulating and excreted anthocyanin metabolites and catabolic products. To date, the bioavailability and health benefits of anthocyanins have been widely documented. Although there are several papers that illustrated the metabolism of anthocyanins, the effects of dietary anthocyanins on the modulation of the gut microbial ecology and on the growth of certain microbial species are still poorly understood. The present paper summarizes the recent data on the absorption of anthocyanins in the upper gastrointestine and the metabolism of anthocyanins by gut microbiota. The modulatory effects of anthocyanins from different sources on gut microbiota are also discussed.

Adducts formed during protein digestion decreased the toxicity of five carbonyl compounds against Caco-2 cells.

Acrolein (ACR), glyoxal (GO), methylglyoxal (MGO), hydroxymethylfurfural (HMF), and malondialdehyde (MDA) are toxic contaminants for humans. This work aimed to investigate whether intake of proteins can mitigate their toxicity. Simulated gastrointestinal digestion of proteins from pork, chicken, milk powder and soy protein isolate eliminated amount of ACR, GO, MGO, HMF, and MDA. Among six amino acids, cysteine showed highest capacity for elimination of these toxic compounds through the formation of adducts; it reached the highest elimination capacity for GO, MGO, ACR, MDA, and HMF in 40 min at pH 2.0, and 20 min at pH 7.0. The formed adducts between cysteine and GO, MGO, or ACR showed much lower toxicity against Caco-2 cells. Incubation of the cells with 8 mM GO and MGO for 48 h decreased the cell viability to 16.1%, 16.9% respectively; while incubation of the same concentration of their adducts still kept the cell viability at 82.2% and 81.6% respectively. Cysteine showed much higher detoxifying capacity for ACR than GO and MGO, which can lower the toxicity of ACR toward Caco-2 cells by 80 times.

Absorption of 1-Dicysteinethioacetal-5-Hydroxymethylfurfural in Rats and Its Effect on Oxidative Stress and Gut Microbiota.

The absorption of a 5-hydroxymethylfurfural (HMF)-cysteine adduct, 1-dicysteinethioacetal-5-hydroxymethylfurfural (DCH), and its effect on antioxidant activity and gut microbiota were investigated. Results indicated that DCH is more easily absorbed in rats than HMF. Serum DCH concentrations were 15-38-fold of HMF concentrations from 30 to 180 min after intragastrical administration at the level of 100 mg/kg of body weight, and 2.7-4.5% of absorbed DCH was converted to HMF. The malondialdehyde content in the plasma, heart, liver, and kidneys significantly increased after drug (100 mg/kg of bw) administration for 1 week, suggesting that HMF and DCH were oxidative-stress-inducing agents, instead of antioxidant agents, in rats. HMF and DCH also modulated gut microbiota. HMF promoted the growth of Lactobacillus, Tyzzerella, Enterobacter, and Streptococcus. DCH increased the ratio of Firmicutes/ Bacteroidetes and promoted the growth of Akkermansia, Shigella, and Escherichia while inhibiting the growth of Lactobacillus.

Applications and perspectives of nanomaterials in novel vaccine development.

Vaccines show great potential for both prophylactic and therapeutic use in infections, cancer, and other diseases. With the rapid development of bio-technologies and materials sciences, nanomaterials are playing essential roles in novel vaccine formulations and can boost antigen effectiveness by operating as delivery systems to enhance antigen processing and/or as immune-potentiating adjuvants to induce or potentiate immune responses. The effect of nanoparticles in vaccinology showed enhanced antigen stability and immunogenicity as well as targeted delivery and slow release. However, obstacles remain due to the lack of fundamental knowledge on the detailed molecular working mechanism and in vivo bio-effects of nanoparticles. This review provides a broad overview of the current improvements in nanoparticles in vaccinology. Modern nanoparticle vaccines are classified by the nanoparticles' action based on either delivery system or immune potentiator approaches. The mechanisms of interaction of nanoparticles with the antigens and the immune system are discussed. Nanoparticle vaccines approved for use are also listed. A fundamental understanding of the in vivo bio-distribution and the fate of nanoparticles will accelerate the rational design of new nanoparticles comprising vaccines in the future.