Dietary Oat ß-Glucan Alleviates High-Fat Induced Insulin Resistance through Regulating Circadian Clock and Gut Microbiome.

SCOPE: High-fat diet induced circadian rhythm disorders (CRD) are associated with metabolic diseases. As the main functional bioactive component in oat, ß-glucan (GLU) can improve metabolic disorders, however its regulatory effect on CRD remains unclear. In this research, the effects of GLU on high-fat diet induced insulin resistance and its mechanisms are investigated, especially focusing on circadian rhythm-related process. METHODS AND RESULTS: Male C57BL/6 mice are fed a low fat diet, a high-fat diet (HFD), and HFD supplemented 3% GLU for 13 weeks. The results show that GLU treatment alleviates HFD-induced insulin resistance and intestinal barrier dysfunction in obese mice. The rhythmic expressions of circadian clock genes (Bmal1, Clock, and Cry1) in the colon impaired by HFD diet are also restored by GLU. Further analysis shows that GLU treatment restores the oscillatory nature of gut microbiome, which can enhance glucagon-like peptide (GLP-1) secretion via short-chain fatty acids (SCFAs) mediated activation of G protein-coupled receptors (GPCRs). Meanwhile, GLU consumption significantly relieves colonic inflammation and insulin resistance through modulating HDAC3/NF-κB signaling pathway. CONCLUSION: GLU can ameliorate insulin resistance due to its regulation of colonic circadian clock and gut microbiome.

Persimmon leaf polyphenols as potential ingredients for modulating starch digestibility: Effect of starch-polyphenol interaction.

The interaction mode between persimmon leaf polyphenols (PLP) and corn starch with different amylose content and its effect on starch digestibility was studied. Results of iodine binding test, TGA, and DSC revealed that PLP interacted with starch and reduced the iodine binding capacity and thermal stability of starch. High amylopectin corn starch (HAPS) interacted with PLP mainly via hydrogen bonds, since the FT-IR of HAPS-PLP complex showed higher intensity at 3400 cm-1 and an obvious shift of 21 cm-1 to shorter wavelength, and the chemical shifts of protons in 1H NMR and the shift of C-6 peak in 13C NMR of HAPS moved to low field with the addition of PLP. Results of 1H NMR also showed the preferential formation of hydrogen bonds between PLP and OH-3 of HAPS. Different from HAPS, PLP formed V-type inclusion complex with high amylose corn starch (HAS) because XRD of HAS-PLP complex showed characteristic feature peaks of V-type inclusion complex and C-1 signal in 13C NMR of PLP-complexed HAS shifted to low field. Interaction with PLP reduced starch digestibility and HAS-PLP complex resulted in more resistant starch production than HAPS-PLP complex. To complex PLP with starch might be a potential way to prepare functional starch with slower digestion.

Hypoglycemic activity in vivo and in vitro of the Lotus (Nelumbo nucifera Gaertn.) seed skin (testa) phenolic-rich extracts.

Lotus (Nelumbo nucifera Gaertn.) seed, a traditional Chinese herbal medicine, exhibits good hypoglycemic activities. However, the bioactive components that are responsible for the biological effects and their underlying mechanisms remain obscure. This study aimed to identify the bioactive components of lotus seed skin phenolic-rich extract (LSSE) and investigate their α-glucosidase inhibitory activity. In vivo study showed that LSSE could significantly decrease the fasting blood glucose levels and the area under the curves with dose-dependent manners in diabetes mellitus mice. And the α-glucosidase activity was decreased by 39.4% after intervention with LSSE. The results also demonstrated that LSSE possessed up to 77.53% rat intestinal maltase inhibitory activity and general sucrase and isomaltase inhibitory activity. A total of 38 phenolic compounds were first quantified in LSSE. Molecular docking analysis further revealed that the bioactive components in LSSE bind with α-glucosidase by hydrogen bonding Van der Waals and hydrophobic interactions. These results indicate the potential use of LSSE for natural hypoglycemic functional foods.

Dietary fiber (oligosaccharide and non-starch polysaccharide) in preventing and treating functional gastrointestinal disorders - Challenges and controversies: A review.

Functional gastrointestinal disorders (FGIDs) are a group of chronic or recurrent gastrointestinal functional diseases, including functional dyspepsia, irritable bowel syndrome, and functional constipation. A lack of safe and reliable treatments for abdominal pain-related FGIDs has prompted interest in new therapies. Evidence has shown that supplementation with dietary fiber may help treat FGIDs. Dietary fibers (DFs) have been demonstrated to have regulatory effects on the gut microbiota, microbiota metabolites, and gastrointestinal movement and have important implications for preventing and treating FGIDs. However, the adverse effects of some DFs, such as fermentable oligosaccharides, on FGIDs are unclear. This review provides an overview of the DFs physiological properties and functional characteristics that influence their use in management of FGIDs, with emphasis on structural modification technology to improve their therapeutic activities. The review highlights that the use of appropriate or novel fibers is a potential therapeutic approach for FGIDs.

Domestic Cooking Affects the Prebiotic Performances of Chinese Yam.

The appropriate domestic cooking methods can retain and protect the biological properties of foods well. Thus, the objective of this study was to unravel the effect of different cooking methods on the microbiota modulatory properties of yam and their non-starch polysaccharides by an in vitro simulated digestion and fermentation model. The results showed that different cooking processes led to different changes in polysaccharide content. The polysaccharide content of yam increased by 21.3~108.2% or decreased by 12.0% compared with that of raw yam. Additionally, the soluble polysaccharides contents in all cooked yam samples significantly increased by 16.85~119.97% after in vitro digestion. The regulation of whole-yam digesta on gut microbiota was partly related with yam polysaccharides. Both yam and yam polysaccharide fermentation appeared to promote beneficial bacteria, such as Bifidobacteria, Bacteroides spp. and Megasphaera and suppressed bacterial pathogens such as Ruminococcusforques and Escherichia-Shigella. Household cooking significantly influenced the prebiotic performances of yam and yam polysaccharides by changing the heat-sensitive microbial substrates and their physiology properties. According to our results, normal-pressure steaming and normal-pressure boiling processes can retain the microbiota modulatory effects of Chinese yam.

Ionic liquid depolymerize the lignocellulose for the enzymatic extraction of feruloylated oligosaccharide from corn bran.

In this study, a new method was developed for feruloylated oligosaccharides (FOs) enzymatic hydrolysis extraction from corn bran, using ionic liquids (ILs) as the solvent for the depolymerization of dietary fiber. The 1-allyl-3-methylimidazolium acetate [Amim]Ac was the most effective IL among the eight evaluated ILs, which leads to a 1.5 times-higher total FOs content as compared with conventional non-pretreatment extraction. The optimum condition acquired by response surface methodology was 194.31 min, 143.08 °C, solid-liquid ratio of 1:20, and the concentration of 18.65%. The depolymerized biomass was characterized using SEM, FTIR and CLSM. The results confirmed that [Amim]Ac mainly enters the cavity among the lignocellulose and breaks linkages to release FOs by exposure binding sites of hemicellulose to hydrolysis enzymes. In particular, the linkages between ferulic acid and hemicellulose were not affected by ILs pretreatment. This study provides an efficient method for the preparation of conjugated phenols from lignocellulose.

Arborinine from Glycosmis parva leaf extract inhibits clear-cell renal cell carcinoma by inhibiting KDM1A/UBE2O signaling.

Background: Arborinine is a natural product isolated from Globigerina parva (G. parva) leaf extract that shows strong anticancer activity with its role in clear-cell renal cell carcinoma (ccRCC) unreported. Objective: We aim to evaluate the role of Arborinine in ccRCC. Design: Arborinine was tested for its effects in ccRCC cell lines in vitro and in silico. Results: Arborinine conferred inhibitory effect to ccRCC cells at reasonable doses. Arborinine showed inhibitory effects on Lysine Demethylase 1A (KDM1A) in ccRCC cells and decreased levels of KDM1A outputs and on epithelial mesenchymal transition (EMT) markers. Arborinine significantly inhibited proliferation, apoptosis, and cell cycle progression and migration of ccRCC cells. Using in silico ChIP analysis and luciferase activity validation, we identified Ubiquitin-conjugating enzyme E2O (UBE2O) as an active transcription target downstream of KDM1A. UBE2O expression was not only correlated with KDM1A expression but also associated with worsened prognosis in ccRCC. Overexpression of UBE2O abrogated cancer-inhibitory effect of Arborinine. Discussion: Arborinine holds promise as an additive in the treatment of ccRCC. Conclusions: We have shown for the first time that Arborinine showed inhibitory effect on ccRCC via KDM1A/UBE2O signaling.

Red-Skin Extracts of Lotus Seeds Alleviate High-Fat-Diet Induced Obesity via Regulating Lipoprotein Lipase Activity.

In recent years, obesity has become an epidemic and an important public health concern. This study was designed to explore the anti-obesity effects of red-skin extracts (RSE) from lotus seeds on high-fat-diet (HFD)-fed mice. In this study, a total of 55 phenolic compounds from the RSE were tentatively characterized using a UPLC-Q/TOF-MS system, including 9 phenolic acids and derivatives, 40 flavonoids, 2 proanthocyanidin, and 4 coumarins and derivatives. Our data demonstrated that RSE could significantly ameliorate obesity characteristics of HFD-fed mice by regulating tissue specific lipoprotein lipase (LPL) activities. In detailed, the activity and expression of LPL in adipose tissue was inhibited, and the activity and expression of LPL in skeletal muscle tissue was enhanced. Overall, these findings suggested that RSE from the red skin of lotus seeds could serve as a great candidate for a value-added, functional ingredient due to its anti-obesity effects via the regulation of LPL activity.

Therapeutic Potential of Natural Products in the Treatment of Renal Cell Carcinoma: A Review.

Renal cell carcinoma (RCC) is a common cancer of the urinary system. The potential therapeutic effects of certain natural products against renal cell carcinoma have been reported both in vivo and in vitro, but no reviews have been published classifying and summarizing the mechanisms of action of various natural products. In this study, we used PubMed and Google Scholar to collect and screen the recent literature on natural products with anti-renal-cancer effects. The main mechanisms of action of these products include the induction of apoptosis, inhibition of angiogenesis, inhibition of metastasis and reduction of drug resistance. In total, we examined more than 30 natural products, which include kahweol acetate, honokiol, englerin A and epigallocatechin-3-gallate, among others, have demonstrated a variety of anti-renal-cancer effects. In conclusion, natural products may have a wider application in kidney cancer than previously believed and are potential candidates for treatment in RCC.

The Progress of Nomenclature, Structure, Metabolism, and Bioactivities of Oat Novel Phytochemical: Avenanthramides.

Oats are among the most commonly consumed whole grains and are widely grown worldwide, and they contain numerous nutrients, including proteins, lipids, vitamins, minerals, ß-glucan, and unique phytochemical polyphenol avenanthramides (Avns). Recent studies have indicated that Avns play essential roles in mediating the health benefits of oats. This review systemically summarized the nomenclature and structures of Avns, effect of germination on promoting Avns production, and in vivo metabolites produced after Avns consumption. The classical functions and novel potential bioactivities of Avns were further elucidated. The classical functions of Avns in cancer prevention, antioxidative response, anti-inflammatory reaction, and maintaining muscle health were expounded, and the internal mechanisms of these functions were analyzed. The potential novel bioactivities of Avns in modulating gut microbiota, alleviating obesity, and preventing chronic diseases, such as atherosclerosis and osteoporosis, were further revealed. This review may provide new prospects and directions for the development and utilization of oat Avns.

In vitro study of the effect of quinoa and quinoa polysaccharides on human gut microbiota.

It has been shown that whole grains and dietary fiber are important for their fermentation characteristics in the large intestine, drawing more and more attention to quinoa and quinoa polysaccharides. In this study, we evaluated the prebiotic effect of quinoa seeds and quinoa polysaccharides after human simulated digestion. The modulatory effect of the quinoa and quinoa polysaccharides (QPs) on the gut microbiota was evaluated by the in vitro fermentation using human fecal microbiota. The yield of polysaccharides extraction was 15.45%. The digestibility of the cooked and uncooked quinoa after simulation of human digestion was 69.04% and 64.09%, respectively. The effect on the microbiota composition and their metabolic products was determined by the assessment of pH, short-chain fatty acids (SCFAs), and changes in the bacterial population. After 24 hr anaerobic incubation, the total SCFAs of cooked, uncooked quinoa, and quinoa polysaccharides were 82.99, 77.11, and 82.73 mM, respectively with a pH decrease. At the phylum, genus, and class level, it has been found that the quinoa substrates enhance the growth of certain beneficial bacteria such as Prevotella and Bacteroides. Quinoa polysaccharides can be considered prebiotic due to their ability to increase Bifidobacterium and Collinsella. Principal component analysis (PCA) showed that there was a distinct modulating effect on the fecal microbiota which represents different distribution. Our research suggests that quinoa and quinoa polysaccharides have a prebiotic potential due to their association with the positive shifts in microbiota composition and short-chain fatty acids production, which highlights the importance of further studies around this topic.

Effects of different household cooking methods on the biological properties of Chinese yam.

Yam (Dioscorea opposite Thunb) is used as a staple food and a traditional medicine in China. This study investigated the effects of different household cooking methods on the bioactive components (phenolic compounds, diosgenin and allantoin) and their bioaccessibility as well as the biological properties (antioxidant activity, hypoglycemic activity, anti-angiotensin I-converting enzyme (ACE) or anti-acetylcholinesterase (AChE)) of Chinese yam using an in vitro simulated digestion model. The results demonstrated that cooking caused significant losses of total soluble phenolic compounds (lowest loss of 20% for boiling at atmospheric pressure) and diosgenin content (lowest loss of 27.37% for microwaving) but no changes in the allantoin content. The cooking methods affected the bioaccessibility of the bioactive components differently. Normal steaming resulted in the highest amount of bioaccessible phenolic compounds (71.21%) and allantoin (79.07%), whereas high-pressure boiling in the highest content of diosgenin (75.58%). The concentration of bioactive components in the digesta fluid was correlated with the antioxidant activity and enzymatic inhibitory activities. Overall, household cooking processes allow the biological activity of yam to be retained by changing the profile of bioactive components potentially available for intestinal absorption. Thus, a household cooking method such as normal pressure steaming appeared to be most suitable for achieving the expected health benefits of yam.

Inhibitors of α-amylase and α-glucosidase: Potential linkage for whole cereal foods on prevention of hyperglycemia.

The strategy of reducing carbohydrate digestibility by controlling the activity of two hydrolyzing enzymes (α-amylase and α-glucosidase) to control postprandial hyperglycemia is considered as a viable prophylactic treatment of type 2 diabetes mellitus (T2DM). Thus, the consumption of foods rich in hydrolyzing enzyme inhibitors is recommended for diet therapy of diabetes. Whole cereal products have gained increasing interests for plasma glucose-reducing effects. However, the mechanisms for whole cereal benefits in relation to T2DM are not yet fully understood, but most likely involve bioactive components. Cereal-derived phenolic compounds, peptides, nonstarch polysaccharides, and lipids have been shown to inhibit α-amylase and α-glucosidase activities. These hydrolyzing enzyme inhibitors seem to make whole cereals become nutritional strategies in managing postmeal glucose for T2DM. This review presents an updated overview on the effects provided by cereal-derived ingredients on carbohydrate digestibility. It suggests that there is some evidence for whole cereal intake to be beneficial in amelioration of T2DM through inhibiting α-glucosidase and α-amylase activities.

Transport, metabolism and remedial potential of functional food extracts (FFEs) in Caco-2 cells monolayer: A review.

Caco-2, a human intestinal carcinoma cell line, has been used to test the absorption and transport mechanism of functional foods and drugs across the intestinal epithelium in order to study their antioxidant, anticancer and anti-inflammatory activities. Caco-2 cells represent the morphological and functional characteristics of small intestinal cells and capable of expressing brush borders, tight junctions, intestinal efflux and uptake transporters which regulate permeation of drugs and functional food extracts from intestinal lumen to systemic circulation. The integrity of the Caco-2 monolayer is controlled by establishing the TEER between 200 and 1000 O per cm2. FFEs affect intestinal permeability by adjusting the tight junction proteins between the cells in order to maintain the epithelial barrier function. Because of the side effects of medicines, there is an increased interest in functional food extracts (FFEs) as drug substitutes. Functional foods undergo intricate transport processes and biotransformation after oral administration. Metabolism and transport studies of FFEs in Caco-2 cells are very important for determining their bioavailability. Functional foods and their constituents produce anti-proliferative and anti-cancer effects through apoptosis, cell cycle arrest and inhibition of various signal transduction pathways across Caco-2 cell lines. The current review has summarized the anti-inflammation, anticancer, antioxidant and cholesterol lowering potential of FFEs using Caco-2 cells through reducing local inflammatory signals, production of ROS and lipid accumulation. The transport, bioavailability, metabolism, mechanisms of actions, cellular pathways adopted by FFEs across Caco-2 cell lines are predominantly affected by their molecular weight, structures and physicochemical properties. These studies are beneficial for investigating the different mechanisms of action of FFEs in the human body.

Role of the Microbiome in Mediating Health Effects of Dietary Components.

Numerous recent observation and intervention studies suggest that the microbiota in the gut and oral cavity play important roles in host physiology, including disease development and progression. Of the many environmental factors involved, dietary components play a pivotal role in shaping the microbiota community and function, thus eliciting beneficial or detrimental consequences on host health. The microbiota affect human physiology by altering the chemical structures of dietary components, thus creating new biological properties and modifying their lifetime and bioavailability. This review will describe the causal mechanisms between the microbiota and some specific bacterial species and diet components providing health benefits and how this knowledge could be incorporated in dietary strategies for improving human health.

Capsanthin extract prevents obesity, reduces serum TMAO levels and modulates the gut microbiota composition in high-fat-diet induced obese C57BL/6J mice.

The present study investigated the anti-obesity effects and its mechanism of capsanthin (CAP) in high-fat diet-induced obese C57BL/6J mice. Compared with untreated mice on a high-fat diet for 12 weeks, CAP at 200 mg kg-1 reduced the body weight by 27.5%, significantly reversed glucose tolerance, effectively decreased the serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and trimethylamine N-oxide levels, markedly increased microbial diversity. Furthermore, 16S rRNA gene sequencing of the cecal microbiota suggested that CAP increased the abundance of Bacteroidetes, Bifidobacterium and Akkermansia, decreased the abundance of Ruminococcus and the ratio of Firmicutes/Bacteroidetes. Moreover, predicted functional domain analysis indicated that CAP increased the gene abundance of replication and repair, and decreased the gene abundance of membrane transports and carbohydrate metabolisms. Therefore, it seems CAP exhibit anti-obesity effect and might be used as a potential agent against obesity.

Whole barley prevents obesity and dyslipidemia without the involvement of the gut microbiota in germ free C57BL/6J obese mice.

Whole barley (WB) consumption is the subject of renewed interest because of its health benefits. However, there are still controversies regarding the mechanisms of the anti-obesity effects of WB. The gut microbiota has recently become a focus of research into obesity-related disorders. Therefore, the aim of this study was to investigate the contribution of the gut microbiota to the anti-obesity effects of WB. Germ-free (GF) C57BL/6J mice underwent gastric inoculation with human feces to obtain human flora-associated (HFA) mice, and then both the GF and HFA mice were fed a high fat diet (HFD) containing 46% WB or refined barley for 9 weeks. Features of obesity and dyslipidemia were compared between the GF and HFA mice and the cecal microbiota was analyzed using next-generation sequencing of microbial 16S rRNA. WB prevents obesity and hypercholesterolemia in the GF and HFA mice. The mechanism may include the inhibition of cholesterol synthesis, because sterol regulatory element-binding protein-1c (SREBP-1c) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) expression was downregulated, and a reduction in cholesterol accumulation, because cholesterol 7α-hydroxylase (CYP7A1) expression was upregulated, independent of the gut microbiota. Furthermore, WB intake enriched a variety of bacterial genera that are negatively associated with obesity, including Bacteroides, Parabacteroides, and Clostridium cluster XIVa, suggesting that WB counteracted gut dysbiosis in obese mice. Thus, WB helps prevent obesity and dyslipidemia via both gut microbiota-dependent and independent mechanisms.

Comparison of Phenolic Compounds and the Antioxidant Activities of Fifteen Chrysanthemum morifolium Ramat cv. 'Hangbaiju' in China.

This study investigated the phenolic compounds of 15 Chrysanthemum morifolium Ramat cv. 'Hangbaiju', including 6 'Duoju' and 9 'Taiju', using high performance liquid chromatography (HPLC). The antioxidant activities of these 'Hangbaiju' were estimated by DPPH, ABTS and FRAP assays. Results show that a total of 14 phenolic compounds were detected in these flowers, including 3 mono-caffeoylquinic acids, 3 di-caffeoylquinic acids, 1 phenolic acid and 7 flavonoids. 'Duoju' and 'Taiju' possess different concentrations of phenolic compounds, and 'Taiju' exhibits higher caffeoylquinic acids and stronger antioxidant activities than 'Duoju'. Caffeoylquinic acids show a strong correlation with the antioxidant activities of the samples. Principal component analysis (PCA) reveals an obvious separation between 'Duoju' and 'Taiju', using phenolic compounds as variables. Apigenin-7-O-glucoside, 3,5-di-O-caffeoylquinic acid, luteolin and acacetin were found to be the key phenolic compounds to differentiate 'Duoju' from 'Taiju'.

Tibet kefir milk decreases fat deposition by regulating the gut microbiota and gene expression of Lpl and Angptl4 in high fat diet-fed rats.

The role of Tibet kefir milk (TKM) feeding on fat deposition was investigated in high-fat diet (HFD)-fed human flora-associated (HFA) rats. TKM feeding reduced abdominal fat mass from 33.9 g to 24.0 g and serum triglyceride (TG) from 0.75 mmol/L to 0.47 mmol/L, and caused lipoprotein lipase (LPL) to decrease from 395.8 ±â€¯36.0 ng/L to 362.3 ±â€¯64.4 ng/L in fat and increase from 287.3 ±â€¯40.8 ng/L to 329.8 ±â€¯48.5 ng/L and 312.5 ±â€¯22.0 to 375.1 ±â€¯30.8 ng/L in liver and serum, respectively. Likewise, TMK feeding down-regulated Lpl gene expression in fat and Angptl4 (angiopoietin-like protein-4, also known as fasting-induced adipose factor) gene expression in liver, and up-regulated Angptl4 gene expression in fat. Sequence analysis showed that the Firmicutes/Bacteroidetes proportion and Verrucomicrobia at the phylum level, Akkermansia, Escherichia and Oscillospira at the genus level, as well as Escherichia coli at the species level were positively regulated by TKM. The results indicated that TKM decreased abdominal fat deposition and serum TG by regulating Lpl and Angptl4 at the transcriptional level. The microbiota groups mentioned above were regulated by TKM at the same time and may be the potential intervention targets to reduce fat deposition.

Corrigendum: Viscoelastic and Functional Properties of Cod-Bone Gelatin in the Presence of Xylitol and Stevioside.

[This corrects the article DOI: 10.3389/fchem.2018.00111.].