Wheat Bran Polyphenols Ameliorate DSS-Induced Ulcerative Colitis in Mice by Suppressing MAPK/NF-κB Inflammasome Pathways and Regulating Intestinal Microbiota.

Wheat bran (WB) is the primary by-product of wheat processing and contains a high concentration of bioactive substances such as polyphenols. This study analyzed the qualitative and quantitative components of polyphenols in wheat bran and their effects on ulcerative colitis (UC) using the dextran sulfate sodium (DSS)-induced colitis model in mice. The potential mechanism of wheat bran polyphenols (WBP) was also examined. Our findings indicate that the main polyphenol constituents of WBP were phenolic acids, including vanillic acid, ferulic acid, caffeic acid, gallic acid, and protocatechuic acid. Furthermore, WBP exerted remarkable protective effects against experimental colitis. This was achieved by reducing the severity of colitis and improving colon morphology. Additionally, WBP suppressed colonic inflammation via upregulation of the anti-inflammatory cytokine IL-10 and downregulation of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in colon tissues. Mechanistically, WBP ameliorated DSS-induced colitis in mice by inhibiting activation of the MAPK/NF-κB pathway. In addition, microbiome analysis results suggested that WBP modulated the alteration of gut microbiota caused by DSS, with an enhancement in the ratio of Firmicutes/Bacteroidetes and adjustments in the number of Helicobacter, Escherichia-Shigella, Akkermansia, Lactobacillus, Lachnospiraceae_NK4A136_group at the genus level. To conclude, the findings showed that WBP has excellent prospects in reducing colonic inflammation in UC mice.

Green Pea (Pisum sativum L.) Hull Polyphenol Extract Alleviates NAFLD through VB6/TLR4/NF-κB and PPAR Pathways.

Green pea hull is a processing byproduct of green pea and rich in polyphenols. Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disease characterized by accumulation of lipids in the liver for which there are no effective treatment strategies. Here, a mouse model of NAFLD induced by a DSS+high-fat diet (HFD) was established to investigate the effect of green pea hull polyphenol extract (EGPH). The results show that EGPH relief of NAFLD was a combined effect, including reducing hepatic fat accumulation, improving antioxidant activity and blood lipid metabolism, and maintaining glucose homeostasis. Increased intestinal permeability aggravated NAFLD. Combined metabolomics and transcriptomic analysis showed that vitamin B6 is the key target substance for EGPH to alleviate NAFLD, and it may be the intestinal flora metabolite. After EGPH intervention, the level of vitamin B6 in mice was significantly increased, and more than 60% in the blood enters the liver, which activated or inhibited PPAR and TLR4/NF-κB signaling pathways to relieve NAFLD. Our research could be a win-win for expanding the use of green pea hull and the search for NAFLD prophylactic drugs.

Multi-omics reveals that green pea (Pisum sativum L.) hull supplementation ameliorates non-alcoholic fatty liver disease via the SHMT2/glycine/mTOR/PPAR-γ signaling pathway.

Diets rich in various active ingredients may be an effective intervention strategy for non-alcoholic fatty liver disease (NAFLD). The green pea hull (GPH) is a processing by-product of green peas rich in dietary fiber and polyphenols. Here, a mouse model of NAFLD induced by DSS + high-fat diet (HFD) was established to explore the intervention effect of the GPH. The results showed that dietary supplements with the GPH can inhibit obesity and reduce lipid accumulation in the mouse liver to prevent liver fibrosis. GPH intervention can improve liver antioxidant capacity, reduce blood lipid deposition and maintain glucose homeostasis. DSS-induced disruption of the intestinal barrier aggravates NAFLD, which may be caused by the influx of large amounts of LPS. A multi-omics approach combining metabolomics and transcriptomic analysis indicated that glycine was the key target and its content was decreased in the liver after GPH intervention, and that dietary supplements with the GPH can relieve NAFLD via the SHMT2/glycine/mTOR/PPAR-γ signaling pathway, which was further supported by liver-associated protein expression. In conclusion, our study demonstrated that dietary GPH can significantly ameliorate NAFLD, and the future development of related food products can enhance the economic value of the GPH.

Bioaccessibility and transport of lentil hull polyphenols in vitro, and their bioavailability and metabolism in rats.

Polyphenol-rich lentil hulls are a valuable by-product. In this study, lentil hulls were subjected to simulated in vitro digestion and caco-2 cell monolayer models to assess the bioaccessibility, transmembrane transport, and a rat model to examine the bioavailability and metabolism in vivo. Polyphenols were increasingly released during the in vitro digestion, and were found to contribute to the increased antioxidant activity. Among the bioaccessible polyphenols, catechin glucoside, kaempferol tetraglucoside, procyanidin dimer and dihydroxybenzoic acid-O-dipentoside were most efficiently transported across the caco-2 membrane, and responsible for promoting intestinal integrity as a result of enhanced expression of tight junction proteins. When ingested by rats, lentil hull polyphenols underwent extensive I and II phase metabolic reactions in vivo, including hydroxylation, methylation, glucuronidation and sulfation. Overall, results of this study showed that lentil hull polyphenols are bioaccessible and bioavailable, and lentil hulls as a by-product can be a valuable ingredient for future functional foods.

The profiles of durian (Durio zibethinus Murr.) shell phenolics and their antioxidant effects on H2O2-treated HepG2 cells as well as the metabolites and organ distribution in rats.

Durian is a nutritious tropical fruit with potent antioxidant, anti-inflammatory, antibacterial and anti-cancer effects. However, the durian shell was mainly discarded as waste, while there were few studies on the characterization of its phenolic profiles, antioxidant activities, and in vivo metabolites. In the present study, a total of 17 compounds were identified in durian shell extract (DSE) by using an ultra-high-performance liquid chromatography coupled with linear ion trap quadrupole Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS/MS), while 33 metabolites were found in rats' plasma, urine and organ. Moreover, DSE could effectively reduce H2O2-induced oxidative damage in HepG2 cells, reduce the expression of Reactive Oxygen Species (ROS), Malondialdehyde (MDA) and Lactate Dehydrogenase (LDH) and inhibit apoptosis by regulating the expression of Bcl-2-Associated X (BAX), B-Cell Lymphoma 2 (BCL-2), Caspase-3 and Caspase-9 genes and proteins related to mitochondrial pathway apoptosis. This is the first comprehensive report on Durian shell phenolics, their metabolic profiles and underlying mechanisms of the in vitro antioxidant activities.

Free and Bound Phenolics of Laird Lentil (Lens culinaris) Hulls and the Anti-inflammatory Activity of their Digestive Products via Crosstalk between NF-κB and Keap1-Nrf2 Signaling Pathways in HT-29 Cells.

Polyphenol-rich Laird lentil hulls are a byproduct of lentil processing. In the present study, free and bound polyphenols in lentil hulls were analyzed with UHPLC-LTQ-OrbiTrap-MS2, and the anti-inflammatory mechanism of their digestive products was explored based on the NF-κB and Keap1-Nrf2 signaling pathways in the HT-29 cell model. In summary, a total of 27 polyphenols and 5 nonphenolic constituents were identified in free and bound fractions, and among them, catechin glucoside, kaempferol tetraglucoside, procyanidin dimer, and dihydroxybenzoic acid-O-dipentoside were the main polyphenols in the digestive products. These digestive products could reduce inflammatory mediators and exert anti-inflammatory activity by inhibiting NF-κB and activating Keap1-Nrf2 signaling pathways, and there was crosstalk between them, which was a mutual inhibition effect. The results show that polyphenols in lentil hulls are a good source of anti-inflammatory ingredients and have a promising development potential.

Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1-Nrf2 Signaling Pathway and Regulating Gut Microbiota.

Inflammatory bowel disease (IBD), with increasing incidence, causes a range of gastrointestinal symptoms and brings distress and impact on the health and lives of patients. The aim of this study was to explore the protective effects of industrially produced rice protein peptides (RPP) on dextran sulfate sodium (DSS)-induced acute colitis in mice and the potential mechanisms. The results showed that RPP treatment alleviated the symptoms of colitis in mice, including weight loss, colon shortening, and injury, decreased the level of disease activity index (DAI), regulated the balance of inflammatory factors and oxidation, activated Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway, regulated the expression of related antioxidant proteases, and promoted the expression of intestinal tight junction proteins. In addition, RPP maintained intestinal mucosal barrier function and alleviated acute colitis caused by DSS treatment in mice by increasing the value of F/B, increasing the relative abundance of beneficial bacteria such as Akkermansia, and regulating the level of short-chain fatty acids. In conclusion, RPP alleviated colitis symptoms through the Keap1-Nrf2 signaling pathway and regulating gut microbiota, which had the potential as dietary supplements or functional foods.

Industrially Produced Rice Protein Ameliorates Dextran Sulfate Sodium-Induced Colitis via Protecting the Intestinal Barrier, Mitigating Oxidative Stress, and Regulating Gut Microbiota.

Inflammatory bowel disease (IBD) poses a threat to health and compromises the immune system and gut microflora. The present study aimed to explore the effects of rice protein (RP) purified from rice dregs (RD) on acute colitis induced by dextran sulfate sodium (DSS) and the underlying mechanisms. Results showed that RP treatment could alleviate the loss of body weight, colon shortening and injury, and the level of disease activity index, repair colonic function (claudin-1, ZO-1 and occludin), regulate inflammatory factors, and restore oxidative balance (malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and total antioxidant capability (T-AOC)) in mice. Also, RP treatment could activate the Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway, mediate the expression of downstream antioxidant protease (NQO-1, HO-1, and Gclc), regulate gut microbiota by enhancing the relative abundance of Akkermansia and increasing the value of F/B, and adjust short-chain fatty acid levels to alleviate DSS-induced colitis in mice. Thus, RP may be an effective therapeutic dietary resource for ulcerative colitis.

Polyphenol Content of Green Pea (Pisum sativum L.) Hull under In Vitro Digestion and Effects of Digestive Products on Anti-Inflammatory Activity and Intestinal Barrier in the Caco-2/Raw264.7 Coculture Model.

Green pea hulls are a byproduct of the processing of green pea and are rich in phenolic substances. In the present study, in vitro digestion, human colonic adenocarcinoma cell line (Caco-2) monolayer, and the Caco-2/macrophage cell lines of the murine origin (Raw264.7) coculture model were established to investigate the release of polyphenols, absorption, and transport of digestive products and their effects on inflammation and intestinal barrier. During the digestive process, polyphenols were constantly released from the pea hulls, reaching the maximum amount in the small intestine (total phenolic content (TPC): 5.41 ± 0.04 mg gallic acid (GAE)/g dry weight (DW)), and the digestive products (800 µg/mL) could reduce the secretion of NO (50.9%), IL-6 (50.6%), and TNF-α (24.6%) and inhibit the mRNA expression of cyclooxygenase-2 (COX-2) (37.2%) and inducible nitric oxide synthase (iNOS) (91.1%) compared with the lipopolysaccharide (LPS) group. A total of 12 phenolic components were quantified by ultraperformance liquid chromatography-linear ion trap orbitrap tandem mass spectrometry (UHPLC-LTQ-OrbiTrap-MS) technology. Kaempferol trihexoside in digestive products could be absorbed and transported (1.25 ± 0.13 ng quercetin/mL). The digestive products could promote the expression of claudin-1 (210.8%), occludin (64.9%), and zonulin occludin-1 (ZO-1) (52.0%) compared with the LPS group and exert anti-inflammatory effects after being absorbed. The results indicated that pea hull polyphenols could be continuously released and absorbed to play a positive role in protecting the intestinal barrier and anti-inflammatory activity.

The Interactional Characterization of Lentil Protein Isolate (LPI) with Cyanidin-3-O-Glucoside (C3G) and Their Effect on the Stability and Antioxidant Activity of C3G.

The interaction between lentil protein isolate (LPI) and cyanidin-3-O-glucoside (C3G) was investigated via with UV−vis spectroscopy, circular dichroism, and fluorescence spectroscopy and the stability of anthocyanin was also evaluated. After LPI mixed with C3G, the turbidity and foaming capacity increased and the particle size and surface charge did not change significantly, while the surface hydrophobicity decreased significantly (p < 0.05). The fluorescence results indicated that C3G quenched the intrinsic of LPI by static quenching and LPI bound with C3G via hydrophobic effects with Ka of 3.24 × 106 M−1 at 298 K. The addition of LPI significantly (p < 0.05) slightly decreased the thermal and oxidation degradation of C3G by up to 90.23% and 54.20%, respectively, while their antioxidant activity was inhibited upon mixing. These alterations of physicochemical properties might be attributed to their structural changes during the interaction. The obtained results would be of help in stabilizing bioactive compounds and the development of functional foods.

Green Pea (Pisum sativum L.) Hull Polyphenol Extracts Ameliorate DSS-Induced Colitis through Keap1/Nrf2 Pathway and Gut Microbiota Modulation.

As a processing by-product, green pea hull (GPH) was found to be rich in phenolic components in our previous studies. In this study, UHPLC-LTQ-OrbiTrap-MS (Ultra performance liquid chromatography-linear ion trap orbitrap tandem mass spectrometry) technique was used to quantify polyphenols, and DSS (sodium dextran sulfate)-induced colitis mouse model was established to explore the effect of GPH extracts on colitis. The results showed that quercetin and its derivatives, kaempferol trihexanside and catechin and its derivatives were the main phenolic substances in the extract, reaching 2836.57, 1482.00 and 1339.91 µg quercetin/g GPH extract, respectively; GPH extracts can improved inflammatory status, repaired colonic function, regulated inflammatory factors, and restored oxidative balance in mice. Further, GPH extracts can activate Keap1-Nrf2-ARE signaling pathway, regulate downstream antioxidant protease and gut microbiota by increasing F/B value and promoting the growth of Lactobacillaceae and Lachnospiraceae, and improve the level of SCFAs (short-chain fatty acids) to relieve DSS-induced colitis in mice. Therefore, GPH may be a promising dietary resource for the treatment of ulcerative colitis.

Metabolism of Phenolics of Tetrastigma hemsleyanum Roots under In Vitro Digestion and Colonic Fermentation as Well as Their In Vivo Antioxidant Activity in Rats.

Tetrastigma hemsleyanum Diels et Gilg is a herbaceous perennial species distributed mainly in southern China. The Tetrastigma hemsleyanum root (THR) has been prevalently consumed as a functional tea or dietary supplement. In vitro digestion models, including colonic fermentation, were built to evaluate the release and stability of THR phenolics with the method of HPLC-QqQ-MS/MS and UPLC-Qtof-MS/MS. From the oral cavity, the contents of total phenolic and flavonoid began to degrade. Quercetin-3-rutinoside, quercetin-3-glucoside, kaempferol-3-rutinoside, and kaempferol-3-glucoside were metabolized as major components and they were absorbed in the form of glycosides for hepatic metabolism. On the other hand, the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, and glutathione (GSH) content were significantly increased, while malondialdehyde (MDA) content was decreased in plasma and tissues of rats treated with THR extract in the oxidative stress model. These results indicated that the THR extract is a good antioxidant substance and has good bioavailability, which can effectively prevent some chronic diseases caused by oxidative stress. It also provides a basis for the effectiveness of THR as a traditional functional food.

Characteristics of rice dreg protein isolate treated by high-pressure microfluidization with and without proteolysis.

The characteristics of rice dreg protein isolate (RDPI) treated by microfluidization (0, 40, 80, 120, and 160 MPa) with or without proteolysis were investigated. Alcalase, Neutrase, and the combination of the two (Alcalcase:Neutrase = 1:1 [w/w]) were adopted for hydrolysis. The surface hydrophobicity and solubility of RDPI were increased. As pressure increased, different structures of RDPI exhibited disaggregation (<120 MPa) and reaggregation (160 MPa), and the effect on proteolysis was significant. The solubility of Neutrase and combined enzyme hydrolysates was improved after microfluidization. Additionally, the optimum choice of microfluidization (40 MPa) and Neutrase was efficient for improving the DPPH radical scavenging activity. The results indicate that both pressure level and enzyme type synergistically determine the functionality and antioxidant activities of products. This work may provide an alternative methodology for improving the utilization of RDPI in the food industry through desirable modifications.

Phenolics of Yellow Pea (Pisum sativum L.) Hulls, Their Plasma and Urinary Metabolites, Organ Distribution, and In Vivo Antioxidant Activities.

As a byproduct, large amounts of yellow pea hull (YPH) are used as low-value or worthless feed worldwide each year, which is a major waste of these polyphenol-rich hulls. The metabolism, bioavailability, and in vivo activities of these polyphenols have not been reported. In the present study, the chemical profiles of YPH extract, their metabolites, and organ distribution were analyzed with UHPLC-LTQ-OrbiTrap-MS, and their in vivo antioxidant activities were studied using the d-gal model in rats. In summary, a total of 42 ingredients were identified in YPH extracts, and 54 metabolites were found in plasma or urine samples. The distribution of metabolites in plasma and organs may have a positive effect on SOD, GSH-Px, MDA, and T-AOC, and the liver and kidneys were the main distribution organs of these metabolites. Our results are of great significance for the development and utilization of the polyphenol-rich hull of yellow pea.

Phenolics of Green Pea (Pisum sativum L.) Hulls, Their Plasma and Urinary Metabolites, Bioavailability, and in Vivo Antioxidant Activities in a Rat Model.

Increased processing of pulses generates large volumes of hulls, which are known as an excellent source of phenolic antioxidants. However, the bioavailability and in vivo activity of these phenolics are rarely reported. This research was therefore carried out to study the absorption, metabolism, and in vivo antioxidant activities of green pea hull (GPH) phenolics using ultrahigh-pressure liquid chromatography with a linear ion trap-high-resolution Orbitrap mass spectrometry and an oxidative stress rat model. A total of 31 phenolics, including 4 phenolic acids, 24 flavonoids, and 3 other phenolics, were tentatively identified. Ten of these phenolics and 49 metabolites were found in the plasma and urine of rats, which helped to explain the favorable changes by GPH phenolics in key antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and glutathione) and indicators (total antioxidant capacity, malondialdehyde) in the plasma and different tissues of rats. This is the first comprehensive report on dry pea hull phenolics and their bioavailability, metabolic profiles, and mechanisms of in vivo antioxidant activities.