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.

Formation and metabolism of 6-(1-acetol)-8-(1-acetol)-rutin in foods and in vivo, and their cytotoxicity.

Methylglyoxal (MGO) is a highly reactive precursor which forms advanced glycation end-products (AGEs) in vivo, which lead to metabolic syndrome and chronic diseases. It is also a precursor of various carcinogens, including acrylamide and methylimidazole, in thermally processed foods. Rutin could efficiently scavenge MGO by the formation of various adducts. However, the metabolism and safety concerns of the derived adducts were paid less attention to. In this study, the optical isomers of di-MGO adducts of rutin, namely 6-(1-acetol)-8-(1-acetol)-rutin, were identified in foods and in vivo. After oral administration of rutin (100 mg/kg BW), these compounds reached the maximum level of 15.80 µg/L in plasma at 15 min, and decreased sharply under the quantitative level in 30 min. They were detected only in trace levels in kidney and fecal samples, while their corresponding oxidized adducts with dione structures presented as the predominant adducts in kidney, heart, and brain tissues, as well as in urine and feces. These results indicated that the unoxidized rutin-MGO adducts formed immediately after rutin ingestion might easily underwent oxidation, and finally deposited in tissues and excreted from the body in the oxidized forms. The formation of 6-(1-acetol)-8-(1-acetol)-rutin significantly mitigated the cytotoxicity of MGO against human gastric epithelial (GES-1), human colon carcinoma (Caco-2), and human umbilical vein endothelial (HUVEC) cells, which indicated that rutin has the potential to be applied as a safe and effective MGO scavenger and detoxifier, and AGEs inhibitor.

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.

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.

Formation of a Hydroxymethylfurfural-Cysteine Adduct and Its Absorption and Cytotoxicity in Caco-2 Cells.

Adducts of 5-hydroxymethylfurfural (HMF)-amino acids are formed during food processing and digestion; the elimination capacity of in vitro intestinal digests of biscuits, instant noodles, and potato crisps for HMF is 652, 727, and 540 µg/g, respectively. However, the safety of these adducts is unknown. In this study, an HMF-cysteine adduct named 1-dicysteinethioacetal-5-hydroxymehtylfurfural (DCH), which was found to be produced in the gastrointestinal tract after HMF intake, was prepared to test its effect toward Caco-2 cells. Compared with HMF, the adduct displayed lower cytotoxicity against Caco-2 cells with an IC50 value of 31.26 mM versus 14.95 mM (HMF). The DCH did not induce cell apoptosis, whereas HMF significantly increased the apoptosis rate after incubation at concentrations of 16, 32, and 48 mM for 72 h. DCH showed an absorption rate considerably lower than that of HMF by Caco-2 cells. Lower absorption of DCH may result in lower toxicity compared with HMF against Caco-2 cells. Intracellular transformation of DCH has been observed.

Protection of feruloylated oligosaccharides from corn bran against oxidative stress in PC 12 cells.

Feruloylated oligosaccharides (FOs) were prepared by autoclaving corn bran in oxalic acid (0.6%) solution, and their protection effects against oxidative stress in pheochromocytoma cells (PC 12) cells were investigated. The FOs samples, which comprised a mixture of feruloylated mono- and dipentoses with 4.88% bound ferulic acid (FA), as well as xylose, arabinose, galactose, and glucose amounting to 46.43, 40.46, 3.76, and 8.68% of the total sugars, respectively, were prepared by autoclaving the pretreated corn bran in 0.6% oxalic acid and then further separated. Antioxidant activity was tested by 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH) scavenging and oxygen radical absorbance capacity (ORAC) methods. Oxidative stress was induced by H2O2 in PC 12 neuronal cell culture model. The results showed that FOs exhibited higher antioxidant activity than free ferulic acid, with an IC50 value of 11 versus 128 µM for DPPH and an ORAC value of 4.77 versus 2.62 µmol Trolox/µmol. Tetrazolium blue assay showed that the addition of FOs with an FA concentration >50 µM significantly increased cell viability after treatment with H2O2. Flow cytometry analysis showed that the addition of FOs at concentrations of 800, 200, and 50 µM significantly decreased the apoptosis rate at the sub-G0 phase from 37.5 to 12.7, 16.2, and 20.9% (P < 0.01), respectively. FOs also significantly decreased the malonic dialdehyde content and lactate dehydrogenase (LDH) activity, but increased superoxide dismutase activity in PC 12 cells treated with H2O2 and prevented the damage of cellular membranes by decreasing the release of LDH to the cultures. The addition of FA at 800 µM showed an effect similar to that of FOs at 200 µM. Therefore, the FOs prepared from corn bran are potential functional ingredients for protection against oxidative stress.

Secondary metabolites of a mangrove endophytic fungus Aspergillus terreus (No. GX7-3B) from the South China Sea.

The mangrove endophytic fungus Aspergillus terreus (No. GX7-3B) was cultivated in potato dextrose liquid medium, and one rare thiophene compound (1), together with anhydrojavanicin (2), 8-O-methylbostrycoidin (3), 8-O-methyljavanicin (4), botryosphaerone D (5), 6-ethyl-5-hydroxy-3,7-dimethoxynaphthoquinone (6), 3ß,5α-dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (7), 3ß,5α,14α-trihydroxy-(22E,24R)-ergosta-7, 22-dien-6-one (8), NGA0187 (9) and beauvericin (10), were isolated. Their structures were elucidated by analysis of spectroscopic data. This is the first report of a natural origin for compound 6. Moreover, compounds 3, 4, 5, 7, 8 and 10 were obtained from marine microorganism for the first time. In the bioactive assays in vitro, compounds 2, 3, 9 and 10 displayed remarkable inhibiting actions against α-acetylcholinesterase (AChE) with IC50 values 2.01, 6.71, 1.89, and 3.09 µM, respectively. Furthermore, in the cytotoxicity assays, compounds 7 and 10 exhibited strong or moderate cytotoxic activities against MCF-7, A549, Hela and KB cell lines with IC50 values 4.98 and 2.02 (MCF-7), 1.95 and 0.82 (A549), 0.68 and 1.14 (Hela), and 1.50 and 1.10 µM (KB), respectively; compound 8 had weak inhibitory activities against these tumor cell lines; compounds 1, 2, 3, 4, 5, 6 and 9 exhibited no inhibitory activities against them.

A new sesquiterpene from the mangrove endophytic fungus Aspergillus terreus (No. GX7-3B).

A new compound 1 (named botryosphaerin F), along with other three known compounds 2 (13,14,15,16-tetranorlabd-7-ene-19,6b:12,17-diolide), 3 (botryosphaerin B) and 4 (LL-Z1271ß), has been isolated from the mangrove fungus Aspergillus terreus (No. GX7-3B). The structure of the new compound was established by analysis of spectroscopic data. The hypothetical biogenic relationship of four sesquiterpene analogues was also described in this paper. Furthermore, in the cytotoxicity assays, compound 1 showed potent inhibiting activity towards MCF-7 and HL-60 cancer cell lines with 50% inhibition of cell growth (IC50) values of 4.49 and 3.43 µM, respectively, and compound 4 exhibited promising activity against HL-60 cell line with an IC50 value of 0.6 µM.

The cytotoxicity and anticancer mechanisms of alterporriol L, a marine bianthraquinone, against MCF-7 human breast cancer cells.

Alterporriol L, a new bianthraquinone derivative, was isolated from a marine fungus Alternaria sp. ZJ9-6B. The cytotoxic activity and anticancer mechanisms of alterporriol L towards breast cancer cells lines were detected using MTT assay, immunofluorescence, and flow cytometry. Simultaneously, the changes in morphological properties of cells were detected before and after treatment with alterporriol L by atomic force microscope (AFM) at a nanometer scale. MTT assay showed that alterporriol L could effectively inhibit the growth and proliferation, and there was a dose-dependent manner of cell death. Moreover, the alterporriol L could induce cancer cell apoptosis or necrosis. Furthermore, the reactive oxygen species, mitochondrial membrane potential, and cytosolic free calcium level were changed after treatment with alterporriol L, suggesting that alterporriol L played vital roles in breast cancer cells through destroying the mitochondrial. And all these alterations are in accord with changes of morphology detected by AFM, which suggested that the AFM is a useful tool to detect the morphological changes of the cancer cells.

Three bianthraquinone derivatives from the mangrove endophytic fungus Alternaria sp. ZJ9-6B from the South China Sea.

Three new bianthraquinone derivatives, alterporriol K (1), L (2) and M (3), along with six known compounds were obtained from extracts of the endophytic fungus Alternaria sp. ZJ9-6B, isolated from the mangrove Aegiceras corniculatum collected in the South China Sea. Their structures were elucidated by one- and two-dimensional NMR spectroscopy, MS data analysis and circular dichroism measurements. Compounds 1, 2 and 3 were first isolated alterporriols with a C-2-C-2' linkage. The crystallographic data of tetrahydroaltersolanol B (7) was reported for the first time. In the primary bioassays, alterporriol K and L exhibited moderate cytotoxic activity towards MDA-MB-435 and MCF-7 cells with IC50 values ranging from 13.1 to 29.1 µM.

Benzofuran derivatives from the mangrove endophytic Fungus Xylaria sp. (#2508).

Three metabolites, named xyloketal J (1), xyloester A (2), and xyloallenolide B (3), together with the known substituted dihydrobenzofuran (4) were isolated from the mangrove endophytic fungus Xylaria sp. (#2508). Structures were determined by spectroscopic methods, mainly 1D and 2D NMR.