Foodborne Titanium Dioxide Nanoparticles Induce Stronger Adverse Effects in Obese Mice than Non-Obese Mice: Gut Microbiota Dysbiosis, Colonic Inflammation, and Proteome Alterations.

The recent ban of titanium dioxide (TiO2 ) as a food additive (E171) in France intensified the controversy on safety of foodborne-TiO2 nanoparticles (NPs). This study determines the biological effects of TiO2 NPs and TiO2 (E171) in obese and non-obese mice. Oral consumption (0.1 wt% in diet for 8 weeks) of TiO2 (E171, 112 nm) and TiO2 NPs (33 nm) does not cause severe toxicity in mice, but significantly alters composition of gut microbiota, for example, increased abundance of Firmicutes phylum and decreased abundance of Bacteroidetes phylum and Bifidobacterium and Lactobacillus genera, which are accompanied by decreased cecal levels of short-chain fatty acids. Both TiO2 (E171) and TiO2 NPs increase abundance of pro-inflammatory immune cells and cytokines in the colonic mucosa, indicating an inflammatory state. Importantly, TiO2 NPs cause stronger colonic inflammation than TiO2 (E171), and obese mice are more susceptible to the effects. A microbiota transplant study demonstrates that altered fecal microbiota by TiO2 NPs directly mediate inflammatory responses in the mouse colon. Furthermore, proteomic analysis shows that TiO2 NPs cause more alterations in multiple pathways in the liver and colon of obese mice than non-obese mice. This study provides important information on the health effects of foodborne inorganic nanoparticles.

[Chemical Constituents from Ethyl Acetate Extract of Psidium guajava Leaves (II)].

OBJECTIVE: To study the chemical constituents from ethyl acetate extract of Psidium guajava leaves. METHODS: The constituents were separated and purified by silica gel and Sephadex LH-20 column chromatography and their structures were identified on the basis of physicochemical properties and spectral data. RESULTS: Eleven compounds were isolated and identified as 6,10,14-trimethyl-2-pentadecanone (1), phytyl-acetate (2), cubenol (3), eucalyptin (4), n-docosanoic acid-p-hydroxy-phenethylol ester (5),8-methyl-5,7- dihydroxy-flavonone (6), 6-methyl-5,7-dihydroxy-flavonone (7), betulinic acid (8), carnosol (9), quercetin (10), and 2,4,6-tirhydroxy- 3,5-dimethyl-diphenylketone-4-O-(6'"-O-galloyl)-ß-D-glucoside (11). CONCLUSION: Compounds 1-9 are isolated from this plant for the first time.

[Spectroscopic characteristics of novel Psidium meroterpenoids isolated from guava leaves].

Recently, novel Psidium meroterpenoids were reported in the guava leaves. According to careful analysis of the spectral data of literatures, the spectroscopic characteristics and biosynthetic pathway of Psidium meroterpenoids were summarized in this paper. The results showed that Psidium meroterpenoids had distinct spectroscopic features and reasonable biosynthetic routines, however the number order of carbon atoms was not consistent in the reported literatures. It was concluded that Psidium meroterpenoids were the characteristic chemical constituents of Psidium guajava Linn.

The bioavailability, absorption, metabolism, and regulation of glucolipid metabolism disorders by quercetin and its important glycosides: A review.

Quercetin and its glycosides (QG), vitally natural flavonoid, have been popular for health benefits. However, the absorption and metabolism affect their bioavailability, and the metabolic transformation alters their biological activities. This review systematically summarizes the bioavailability and pathways for the absorption and metabolism of quercetin/QG in vivo and in vitro, the biological activities and mechanism of quercetin/QG and their metabolites in treating glucolipid metabolism are discussed. After oral administration, quercetin/QG are mainly absorbed by the intestine, undergo phase II metabolism in the small intestine and liver to form conjugates and are metabolized into small phenolic acids by intestinal microbiota. Quercetin/QG and their metabolites exert beneficial effects on regulating glucolipid metabolism disorders, including improving insulin resistance, inhibiting lipogenesis, enhancing thermogenesis, modulating intestinal microbiota, relieving oxidative stress, and attenuating inflammation. This review enhances understanding of the mechanism of quercetin/QG regulate glucolipid metabolism and provides scientific support for the development of functional foods.

Inhibitory effects and reactions of gallic acid, catechin, and procyanidin B2 with nitrosation under stomach simulating conditions.

Nitrite widely exists in meat products, and has the functions of bacteriostasis, antisepsis, and color development. However, in an acidic environment, nitrite will react with amines, and further generate nitrosamines with carcinogenic and teratogenic effects. Polyphenols have good antioxidant and nitrite-scavenging effects. This study aimed to evaluate the inhibitory effects of gallic acid, catechin, and procyanidin B2 on the nitrosation reaction under stomach simulating conditions and discuss the potential inhibitory mechanism. The nitrite scavenging rate and nitrosamine synthesis blocking rate of gallic acid, catechin, and procyanidin B2 under different reaction times and contents was determined by UV-vis spectrophotometry. The possible products of the reaction of the three polyphenols with nitrite were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) to reveal the mechanism of inhibiting nitrification. The results showed that the scavenging rate of the three polyphenols on nitrite and the blocking rate of nitrosamine synthesis increased with the increase of the content and reaction time. The ability of the three polyphenols to inhibit nitrosation was catechin > procyanidin B2 > gallic acid. HPLC-MS analysis showed that under simulated gastric juice conditions, the three phenolics were oxidized by nitrous acid to form their semiquinone radicals as the intermediates and nitrosated derivatives, while nitrite might be converted to ˙NO. These results suggested that gallic acid, catechin, and procyanidin B2 could inhibit nitrosation reactions in an acidic environment and may be used as food additives to reduce nitrite residues and nitrosamines in food.

Influence of gardenia yellow on in vitro slow starch digestion and its action mechanism.

This study aimed to explore the influence of gardenia yellow on in vitro wheat starch digestion. The influence of gardenia yellow on the digestion properties of starch was determined through in vitro digestion, and its action mechanism on slow starch digestion was revealed by laser scanning confocal microscopy, enzymatic inhibition dynamics, and other means of characterization. Results showed that gardenia yellow could inhibit starch digestion, significantly increase the resistant starch and slowly digestible starch contents in starch (P < 0.05), and trigger the decrease in glycemic and hydrolysis indices. Furthermore, gardenia yellow could spontaneously bind to the catalytic sites of α-amylase and α-glucosidase, affect their secondary structures through vdW force and hydrophobic interaction, and reduce their catalytic abilities to inhibit the digestion process of wheat starch. Therefore, the interactions of gardenia yellow with starch and digestive enzymes jointly promote the slow digestion of starch.

Dietary citrus peel essential oil ameliorates hypercholesterolemia and hepatic steatosis by modulating lipid and cholesterol homeostasis.

Citrus peel essential oil (CPEO) contains abundant volatile compounds and exhibits fragrance properties and beneficial pharmacological effects on humans. Herein, we aimed to investigate the effects of CPEO on the prevention of hypercholesterolemia and hepatic steatosis in high-fat diet-fed rats and identify its possible regulatory mechanisms in lipid metabolism by combining lipidomics with gene expression analysis. CPEO at effective supplementation levels of 0.5% and 0.75% significantly ameliorated hypercholesterolemia and hepatic steatosis, including decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), hepatic TC and triglyceride (TG) levels, and hepatic lipid droplet accumulation. Lipidomics analysis revealed that the total levels of fatty acid (FFA), TG and cholesteryl ester (CE) classes in the liver tissue were remarkably decreased after 0.75% CPEO supplementation some of which (3 TGs and 4 CEs) might emerge as potential lipid biomarkers in response to the effects of CPEO. Furthermore, these lipidomics findings were associated with downregulation of lipogenesis-related genes SREBP-1c, ACC and FAS and upregulation of bile acid biosynthesis-related genes LXRα, CYP7A1 and CYP27A1 in the liver. This study indicated that CPEO could effectively prevent hypercholesterolemia and hepatic steatosis, possibly because of its mediation of lipid and cholesterol homeostasis by altering liver lipid metabolites and regulating lipid metabolism-related genes.

Hepatic Lipidomics Analysis Reveals the Antiobesity and Cholesterol-Lowering Effects of Tangeretin in High-Fat Diet-Fed Rats.

Tangeretin (TAN) exhibited antilipogenic, antidiabetic, and lipid-lowering effects. However, the lipid biomarkers and the underlying mechanisms for antiobesity and cholesterol-lowering effects of TAN have not been sufficiently investigated. Herein, we integrated biochemical analysis with lipidomics to elucidate its efficacy and mechanisms in high-fat diet-fed rats. TAN at supplementation levels of 0.04 and 0.08% not only significantly decreased body weight gain, serum total cholesterol, and low-density lipoprotein cholesterol levels but also ameliorated hepatic steatosis. These beneficial effects were associated with the declining levels of fatty acids, diacylglycerols (DGs), triacylglycerols, ceramides, and cholesteryl esters by hepatic lipidomics analysis, which were attributed to downregulating lipogenesis-related genes and upregulating lipid oxidation- and bile acid biosynthesis-related genes. Additionally, 21 lipids were identified as potential lipid biomarkers, such as DGs and phosphatidylethanolamines. These findings indicated that the modulation of lipid homeostasis might be the key pathways for the mechanisms of TAN in the antiobesity and cholesterol-lowering effects.

Immobilization of Aspergillus niger lipase onto a novel macroporous acrylic resin: Stable and recyclable biocatalysis for deacidification of high-acid soy sauce residue oil.

Deacidification of high-acid soy sauce residue (SSR) oil is crucial to utilization of SSR oil. Aspergillus niger lipase (ANL) has been widely applied for such purpose while its immobilization still has large room for improvement. ANL was immobilized onto six different macroporous acrylic resins, accounting the effect of the different textural properties of resins on stability and their potential for application in enzymatic deacidification. The resin MARE with lower porosity, higher bulk density, and medium hydrophobicity, was chosen as the best carrier for the best thermostability and reusability. ANL-MARE is a promising catalyst than Novozym 40086, which not only exhibited higher deacidification activity and good thermostability, but also was continuously reused for 15 cycles and efficiently catalyzed from high-acid SSR oil into diacylglycerol-enriched oil. Therefore, immobilized ANL was a novel, low-cost and recyclable biocatalyst that could be used as a good alternative to higher-cost commercial lipases in industrial applications.

Extraction, structural characterization, and immunobiological activity of ABP Ia polysaccharide from Agaricus bisporus.

The extraction, purification, immunobiological activities, and structure of Agaricus bisporus polysaccharides (ABP) were investigated. Especially we purified and identified the polysaccharides with the highest in vitro immunobiological activity. The extraction conditions of ABP were optimized using single factor and orthogonal experiment. ABP Ia was screened after double purification with DEAE-52 and Sephadex G-200 and showed the best immunoregulatory activity. UV spectra analysis and high-performance gel permeation chromatography results indicated that the ABP Ia fraction did not contain any proteins or nucleotides and was a homogeneous polysaccharide with a relative molecular weight of 784 kDa. Gas chromatography mass spectroscopy results showed that ABP Ia was a heteropolysaccharide consisting of ribose, rhamnose, arabinose, xylose, mannose, glucose, and galactose at a molar ratio of 2.08:4.61:2.45:22.25:36.45:89.22:1.55. FT-IR and periodic acid oxidation analysis indicated that ABP Ia was an α-pyran polysaccharide composed of 1 â†’ 2 and 1 â†’ 4 glycosidic bonds, as well as a possible 1 â†’ 3 glycosidic bond. Furthermore, atomic force microscopy revealed that ABP Ia polysaccharide chains twisted to form a rod-like architecture and, at a 5% concentration, aggregated into a tight structure similar to the shape of a stone forest. These findings identify ABP Ia as a potential functional food ingredient or pharmaceutical for immunoregulation.

Identification of a new benzophenone from Psidium guajava L. leaves and its antineoplastic effects on human colon cancer cells.

Psidium guajava L. leaves have a long history of being consumed as herbal teas in many countries. The aim of this study was to identify compounds with anticancer potentials from Psidium guajava L. leaves. Utilizing various extraction and chromatographical techniques, we have isolated one new (2) and two known compounds (1, 3). Structural analyses by the spectroscopic methods of TOF-MS, 1H NMR, 13C NMR, HSQC, and HMBC identified these three compounds as guavinoside E (1), 3,5-dihydroxy-2,4-dimethyl-1-O-(6'-O-galloyl-ß-d-glucopyranosyl)-benzophenone (2), and guavinoside B (3). Cell viability assays showed that compounds 2 and 3 inhibited the growth of HCT116 human colon cancer cells in a dose-dependent manner, where compound 2 was more potent than compound 3. Based on flow cytometry analysis, compound 2 showed stronger activity in inducing cellular apoptosis in cancer cells than compound 3. Furthermore, compounds 2 and 3 modulated expression levels of key proteins involved in cell proliferation and apoptotic signaling. Specifically, compound 2 increased the levels of p53, p-ERK1/2, p-JNK, and cleaved caspases 8 and 9, and compound 3 increased the levels of p53 and cleaved caspase 8. Overall, this study provided identities of three bioactive compounds from P. guajava L. leaves and their anti-cancer effects against human colon cancer cells, which could facilitate the utilization of these compounds and P. guajava L. leaves as potential chemoprevention agents against colon carcinogenesis.

Hepatic transcriptome and proteome analyses provide new insights into the regulator mechanism of dietary avicularin in diabetic mice.

Many dietary flavonoids existing as glycosides in fruits and vegetables are considered bioactive food components with various potential health benefits. Type 2 diabetes mellitus (T2DM) is a complex and polygenic disease with increasing global prevalence and economic burden. In this study, the hypoglycemic effect of avicularin (quercetin-3-O-α-arabinofuranoside), a flavonoid glycoside commonly found in natural plants and fruits, was determined in a high fat diet/streptozotocin induced type 2 diabetes mouse model. Our results demonstrated that dietary avicularin treatment reduced levels of fasting blood glucose, serum TG and LDL-C, liver AST and ALT, and increased hepatic glycogen in T2DM mice. Furthermore, we used RNA-Seq and iTRAQ to compare the gene and protein expression in the livers of the normal control mice (NC), diabetic control mice (DC) and avicularin treated mice (DA100). The differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were analyzed based on gene annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Integrated analysis of the RNA-Seq and iTRAQ data indicated that the fifteen DEGs/DEPs showed the same trend in mRNA and protein expression levels in comparisons of both NC vs DC and DC vs DA100. KEGG analysis revealed that four DEGs/DEPs (PKM, PEPCK, PYG, and PLA2) in the glycolysis, gluconeogenesis, and arachidonic acid pathway, and six DEPs (Ndufb4, Ndufa6, Cox5a, Cox5b, Cox6c, and ATPSß) in the oxidative phosphorylation signaling pathway, play important roles in avicularin's hypoglycemic effect. We also found six other DEGs/DEPs related to T2DM (CA1, Serpinb6a, AK, Pcolce, Cand2, and Atp2a3), and five related to cancer (Phgdh, Tes, Papss1, Psat1, and Fam49b). We did further verify by qRT-PCR and explored the possible binding modes of avicularin with targeted proteins with molecular docking simulations. Taken together, our results demonstrated the protective effects of avicularin against diabetes and provided a global view about the system-level hypoglycemic mechanisms of avicularin by the comprehensive analysis of transcriptomic and proteomic data in T2DM mice.

Dietary Intake of Whole Strawberry Inhibited Colonic Inflammation in Dextran-Sulfate-Sodium-Treated Mice via Restoring Immune Homeostasis and Alleviating Gut Microbiota Dysbiosis.

Strawberry (Fragaria chiloensis) is a major edible berry with various potential health benefits. This study determined the protective effects of whole strawberry (WS) against dextran-sulfate-sodium-induced colitis in mice. In colitic mice, dietary WS reduced the disease activity index, prevented the colon shortening and spleen enlargement, and alleviated the colonic tissue damages. The abundance of proinflammatory immune cells was reduced by dietary WS in the colonic mucosa, which was accompanied by the suppression of overproduction of proinflammatory cytokines. Western blotting and immunohistochemical analysis revealed that dietary WS decreased the expression of proinflammatory proteins in the colonic mucosa. Moreover, dietary WS partially reversed the alteration of gut microbiota in the colitic mice by increasing the abundance of potential beneficial bacteria, e.g., Bifidobacterium and Lactobacillus, and decreasing the abundance of potential harmful bacteria, e.g., Dorea and Bilophila. Dietary WS also restored the decreased production of short-chain fatty acids in the cecum of the colitic mice. The results revealed the anti-inflammatory effects and mechanisms of dietary WS in the colon, which is critical for the rational utilization of strawberry for the prevention of inflammation-driven diseases.

Prevention of Obesity and Hyperlipidemia by Heptamethoxyflavone in High-fat Diet-induced Rats.

Polymethoxyflavones (PMFs) have been shown to prevent obesity, ameliorate type 2 diabetes, and regulate lipid metabolism in vitro and in vivo. However, little is known about the contribution of 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) to prevent obesity and regulate lipid metabolism in vivo. We aimed to investigate the potential efficacy of HMF on preventing obesity and hyperlipidemia in rats fed a high-fat diet (HFD) and its underlying mechanisms. Male Sprague-Dawley rats were fed a normal diet or an HFD with or without HMF (0.02%, 0.04% and 0.08%, w/w) for 6 weeks. The supplementation of HMF not only significantly decreased body weight gain (HFD, 336.50 ± 18.84 g; LHMF, 309.43 ± 20.74 g; MHMF, 296.83 ± 13.88 g; HHMF, 265.71 ± 19.09 g; respectively, p < 0.05) and adipose tissues weight ( p < 0.05), but also markedly lowered serum levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol ( p < 0.05) in the sixth week in a dose-dependent manner compared with the HFD group. HMF also significantly alleviated hepatic steatosis in the liver (liver weight g/100 g body weight of HFD, 4.86 ± 0.11%; LHMF, 4.02 ± 0.33%; MHMF, 4.05 ± 0.31%; HHMF, 3.72 ± 0.34%; respectively, p < 0.05). Furthermore, transcriptome analysis and real-time quantitative RT-PCR demonstrated that HMF supplementation markedly downregulated hepatic genes related to adipogenesis transcription and inflammatory responses, and significantly upregulated genes related to fatty acid oxidation and energy expenditure. These results indicated that HMF could effectively prevent obesity and hyperlipidemia by regulation of the expression of lipid metabolism-related and inflammatory response-related genes.

Novel skeleton sesquiterpenoids isolated from guava leaves.

A chemical investigation of the plant Psidium guajava L., collected in Guangdong province, afforded two novel skeleton sesquiterpenoids 1 and 2. Compound 2 also known as isocaryolan-9-one was a new natural product. The structure of the novel compound 1 was determined as guavacid A by various spectroscopic methods. A possible biosynthetic pathway for 1 and 2 was proposed.

Physicochemical characterisation of the supramolecular structure of luteolin/cyclodextrin inclusion complex.

The formation of supramolecular inclusion complexes between luteolin and five cyclodextrins namely ß-cyclodextrin (ß-CD), methyl-ß-cyclodextrin (M-ß-CD), hydroxyethyl-ß-cyclodextrin (HE-ß-CD), hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and glucosyl-ß-cyclodextrin (G-ß-CD) was investigated. Results from phase-solubility studies showed that luteolin formed 1:1 stoichiometric inclusion complexes with these cyclodextrins with the G-ß-CD complex displaying the greatest stability constant. The supramolecular structure of the luteolin/G-ß-CD complex was investigated by ultraviolet-visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Results showed clearly the formation of a supramolecular complex in which the guest molecule, luteolin, was entrapped inside the cavity of the host, G-ß-CD. The close association between luteolin and G-ß-CD resulted in changes in some of the characteristic spectral, phase transitional and morphological properties of luteolin. Furthermore, molecular docking study showed that the complex was formed with the B ring of luteolin inserted into the cavity of G-ß-CD.

Physicochemical [corrected] properties of the inclusion complex of puerarin and glucosyl-ß-cyclodextrin.

Puerarin is a natural isoflavone, found in the Chinese medicinal plant Ge-gen, with many reported health-promoting properties. However, its low water solubility impedes its application in pharmaceutical and functional food products. This study explores the formation of inclusion complex between puerarin and glucosyl-ß-cyclodextrin (G-ß-CD) to improve the aqueous solubility of puerarin. The complex was prepared by mixing an equal molar mixture of puerarin and G-ß-CD for 24 h, followed by freeze-drying. The obtained complex was analyzed by ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, X-ray diffractometry, and proton nuclear magnetic resonance spectroscopy. Results showed clearly that the process led to the formation of a supramolecular complex in which the guest molecule, puerarin, was entrapped inside the cavity of the host, G-ß-CD. The close association between puerarin and G-ß-CD resulted in changes in some of the characteristic spectral, phase-transitional, and morphological properties of puerarin.