Molecular Mechanism of Pasteurized Akkermansia muciniphila in Alleviating Type 2 Diabetes Symptoms.

Type 2 diabetes (T2DM) significantly diminishes people's quality of life and imposes a substantial economic burden. This pathological progression is intimately linked with specific gut microbiota, such as Akkermansia muciniphila. Pasteurized A. muciniphila (P-AKK) has been defined as a novel food by the European Food Safety Authority and exhibited significant hypoglycemic activity. However, current research on the hypoglycemic activity of P-AKK is limited to the metabolic level, neglecting systematic exploration at the pathological level. Consequently, its material basis and mechanism of action for hypoglycemia remain unclear. Drawing upon this foundation, we utilized high-temperature killed A. muciniphila (H-K-AKK) with insignificant hypoglycemic activity as the control research object. Assessments were conducted at pathological levels to evaluate the hypoglycemic functions of both P-AKK and H-K-AKK separately. Our study unveiled for the first time that P-AKK ameliorated symptoms of T2DM by enhancing the generation of glucagon-Like Peptide 1 (GLP-1), with pasteurized A. muciniphila total proteins (PP) being a pivotal component responsible for this activity. Utilizing SDS-PAGE, proteomics, and molecular docking techniques, we deeply analyzed the material foundation of PP. We scientifically screened and identified a protein weighing 77.85 kDa, designated as P5. P5 enhanced GLP-1 synthesis and secretion by activating the G protein-coupled receptor (GPCR) signaling pathway, with free fatty acid receptor 2 (FFAR-2) being identified as the pivotal target protein for P5's physiological activity. These findings further promote the widespread application of P-AKK in the food industry, laying a solid theoretical foundation for its utilization as a beneficial food ingredient or functional component.

Akkermansia muciniphila: a potential candidate for ameliorating metabolic diseases.

Metabolic diseases are comprehensive disease based on obesity. Numerous cumulative studies have shown a certain correlation between the fluctuating abundance of Akkermansia muciniphila and the occurrence of metabolic diseases. A. muciniphila, a potential probiotic candidate colonized in the human intestinal mucus layer, and its derivatives have various physiological functions, including treating metabolic disorders and maintaining human health. This review systematically explicates the abundance change rules of A. muciniphila in metabolic diseases. It also details the high efficacy and specific molecules mechanism of A. muciniphila and its derivatives in treating obesity, type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease.

Applications, challenges and prospects of bionic nose in rapid perception of volatile organic compounds of food.

Bionic nose, a technology that mimics the human olfactory system, has been widely used to assess food quality due to their high sensitivity, low cost, portability and simplicity. This review briefly describes that bionic noses with multiple transduction mechanisms are developed based on gas molecules' physical properties: electrical conductivity, visible optical absorption, and mass sensing. To enhance their superior sensing performance and meet the growing demand for applications, a range of strategies have been developed, such as peripheral substitutions, molecular backbones, and ligand metals that can finely tune the properties of sensitive materials. In addition, challenges and prospects coexist are covered. Cross-selective receptors of bionic nose will help and guide the selection of the best array for a particular application scenario. It provides an odour-based monitoring tool for rapid, reliable and online assessment of food safety and quality.

Fully nondestructive analysis of capsaicinoids electrochemistry data with deep neural network enables portable system.

Electrochemical methods have been extensively applied for the detection of chemical information from food or other analytes. However, existing electrochemical methods are limited to focusing solely on the absorption peaks and disregard much of the hidden chemical fingerprint information. Consequently, electrochemical sensors are constrained by their ability to detect samples containing multiple source-material mixtures with overlapping constituents. We hypothesized that the target substances can be effectively identified and detected using differential sensor data combined with artificial intelligence (AI). In this study, we developed a novel signal array composed of five metal electrodes and used a convolutional neural network (CNN) model for feature extraction to detect capsaicinoids in stews. Our results indicate that the proposed method achieved satisfactory predictions with a root mean square error (RMSE) of 5.407 in independent brine samples. This provides a promising strategy and practical approach for the nondestructive analysis of multidimensional electrochemical data of mixed analytes.

Red raspberry supplementation mitigates alcohol-induced liver injury associated with gut microbiota alteration and intestinal barrier dysfunction in mice.

Alcoholic liver disease (ALD) is still a global health concern. Long-term alcohol intake alters the gut microbiota diversity and metabolic activity, and causes intestinal barrier dysfunction, leading to the development of ALD. This research explored the protective effects and underlying mechanisms of red raspberry (RR) on alcohol-related disorders in mice. Male C57BL/6J mice were fed a standard diet or a standard diet supplemented with 2%, 4%, and 8% weight/weight RR. Meanwhile, mice were administered 35% (v/v) ethanol (EtOH, 10 mL per kg body weight) intragastrically once daily for six weeks, except the control group mice. The results showed that RR supplementation decreased liver injury markers (alanine and aspartate transaminases) in the serum, reduced triglyceride level in the liver and downregulated hepatic cytochrome P450 2E1 mRNA expression in mice administered EtOH. In addition, EtOH-mediated oxidative stress in the liver was attenuated by RR supplementation through decreased hepatic malondialdehyde content and increased antioxidant (glutathione, glutathione peroxidase, and catalase) levels and activities in mice exposed to EtOH. Moreover, RR supplementation reversed EtOH-induced alteration in the cecal microbial composition at the phylum, order, genus, and species levels and improved the intestinal barrier function associated with the inhibition of the NF-κB/MLCK pathway, which was accompanied by upregulation of tight junctions (zonula occludens 1, occludin, claudin-1, and claudin-4) and E-cadherin mRNA and protein expressions. Accordingly, RR supplementation resulted in a decreased level of endotoxins in the serum and attenuation of the inflammatory response in the liver, illustrated by a significant decrease in tumor necrosis factor-alpha, interleukin (IL)-1ß, and IL-6 levels. Overall, RR supplementation alleviated the adverse effects of chronic alcohol intake in C57BL/6J mice and could be a potential supplement for improving ALD.

Senegalia macrostachya seed polysaccharides attenuate inflammation-induced intestinal epithelial barrier dysfunction in a Caco-2 and RAW264.7 macrophage co-culture model by inhibiting the NF-κB/MLCK pathway.

The intestinal barrier dysfunction associated with chronic inflammation is a major health concern. This work aimed to investigate the protective effect and molecular mechanism of Senegalia macrostachya seed polysaccharide fraction (SMSP2) on inflammation-induced barrier dysfunction using Caco-2 cells and RAW264.7 macrophage co-culture model. The results showed that LPS stimulation of the basolateral RAW264.7 compromised the integrity of the apical differentiated Caco-2 cells monolayer, resulting in decreased transepithelial electrical resistance (TER) and increased inflammatory markers. SMSP2 apical treatment maintained a higher TER value and reduced the epithelial permeability to lucifer yellow (LY) dye. In addition, the SMSP2 group showed a significant decrease in the mRNA level of inflammatory factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin (IL)-8, and tumor necrosis factor-α (TNF-α) in the Caco-2 monolayer compared to the LPS group. Moreover, SMSP2 increased the expression of the tight junctions (TJ) zonula occludens (ZO-1), occludin, and claudin-1 at the mRNA and protein levels. Furthermore, the immunofluorescence assay showed that SMSP2 ameliorated the overall distribution of the TJ proteins in the Caco-2 monolayer. SMSP2 application also resulted in the downregulation of the nuclear factor kappa-B (NF-κB) phosphorylation and the myosin light chain kinase (MLCK) expression, which implies that SMSP2 preserved the monolayer integrity from the inflammation-induced barrier disruption through the inhibition of the NF-kB-mediated MLCK signaling pathway activation. Senegalia macrostachya seeds could therefore be a promising functional food that could be used to improve intestinal barrier function.

Correction: Green sweet potato leaves increase Nrf2-mediated antioxidant activity and facilitate benzo[a]pyrene metabolism in the liver by increasing phase II detoxifying enzyme activities in rats.

Correction for 'Green sweet potato leaves increase Nrf2-mediated antioxidant activity and facilitate benzo[a]pyrene metabolism in the liver by increasing phase II detoxifying enzyme activities in rats' by Ray-Yu Yang et al., Food Funct., 2022, https://doi.org/10.1039/d2fo01049f.

Green sweet potato leaves increase Nrf2-mediated antioxidant activity and facilitate benzo[a]pyrene metabolism in the liver by increasing phase II detoxifying enzyme activities in rats.

Sweet potato leaves (SPL) are a valuable source of phytonutrients with nutritional and various health-promoting benefits. This study evaluated the effects of green and purple SPL supplementation on hepatic xenobiotic-metabolizing enzymes (XME) and membrane transporters, and benzo[a]pyrene (B[a]P) metabolism and B[a]P accumulation in rats. The experiments were conducted in standard and B[a]P-treated rat models. The first experiment showed that rats fed a diet containing 5% (w/w) green or purple SPL for two weeks showed increased hepatic activity of cytochrome P-450 (CYP)1A1/1A2 and glutathione S-transferase. Green SPL supplementation also increased the CYP2C, CYP2D and CYP3A and multidrug resistance-associated protein 2 levels in the liver. Notably, green and purple SPL induced nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 protein expression and reduced oxidative stress in the liver. The second experiment was to evaluate the effects of green and purple SPL supplementation on B[a]P metabolism and B[a]P accumulation in rats. Rats were fed SPL diets (the same as experiment I) for two weeks. When rats were exposed to a single dose (25 mg per kg BW) of B[a]P, green SPL had no effect on B[a]P-induced elevation of CYP1A1 activity but induced GST activity in the intestinal mucosa and the liver. Green SPL also increased hepatic UDP-glucuronosyltransferase activity and reduced B[a]P levels in the plasma, liver, and intestinal mucosa. A lower plasma 8-hydroxy-2'-deoxyguanosine level was found after B[a]P treatment only in the green SPL group. This study suggests that, in the standard rat model, green and purple SPL may increase Nrf2-mediated antioxidant activity and facilitate the xenobiotic detoxification process by increasing hepatic XME and transporters. When exposed to B[a]P, however, only green SPL consumption may increase hepatic B[a]P metabolism and lower the B[a]P level in the liver by increasing phase II detoxifying enzyme activities.

Apigenin glycosides from green pepper enhance longevity and stress resistance in Caenorhabditis elegans.

Peppers are a rich source of bioactive compounds with several health benefits. However, most of the knowledge about these benefits has been obtained through in vitro studies, and less is known about their in vivo health-promoting and stress resistance effects. Therefore, we hypothesized that the intake of apigenin glycosides (XAp-G) from Xiaomila green pepper (Capsicum frutescens) could protect against stress factors and promote longevity of Caenorhabditis elegans. Synchronized worms were treated with XAp-G and the lifespan and stress resistance were examined. XAp-G treatment strongly enhanced the average lifespan of worms by 23.9% compared with control by reducing the reactive oxygen species (ROS) level. Ultrahigh performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectometry analysis showed that Xiaomila pepper (polyamide fraction) contained significant amount of flavone glycosides with m/z 563.14 (apigenin glycosides). Green fluorescent protein fluorescence and real-time polymerase chain reaction analyses showed that XAp-G-treatment could regulate the expression of anti-aging related genes, including daf-2, daf-16, sod-3, hsp-16.2, skn-1, gst-4, gcs-1, jnk-1, and sir-2.1 in C elegans, thereby promoting the translocation of DAF-16 and SKN-1 into the nucleus. However, it could not extend the lifespan of daf-16, skn-1, and sir-2.1 knocked-down mutants. XAp-G treatment significantly reduced ROS under normal and stress conditions (juglone, hydrogen peroxide), and thereby promotes longevity of C elegans via the insulin/insulin-like growth factor-1 signaling pathway.

Vitexin and Isovitexin Act through Inhibition of Insulin Receptor to Promote Longevity and Fitness in Caenorhabditis elegans.

SCOPE: Vitexin and isovitexin are natural plant nutraceuticals for human health and longevity. This research investigates the underlying mechanisms of vitexin and isovitexin on aging and health. The vital role of DAF-2/insulin-like growth factor-1 receptor (IGFR) is illustrated in the insulin/insulin-like growth signaling pathway (IIS) modulated by vitexin and isovitexin. METHODS AND RESULTS: In vitro, in vivo models and molecular docking methods are performed to explore the antiaging mechanism of vitexin and isovitexin. Vitexin and isovitexin (50 and 100 µM) extended the lifespan of Caenorhabditis elegans. The declines of pharyngeal pumping and body bending rates, and the increase of intestinal lipofuscin accumulation, three markers of aging, are postponed by these compounds. They inhibit IIS pathway in a daf-16-dependent manner, subsequently increasing the expressions of DAF-16 downstream protein and gene in nematodes. Molecular docking studies demonstrate that these compounds mightinhibit insulin signal by binding to the crucial amino acid residue ARG1003 in the pocket of IGFR. Western blot indicates that IGFR, PI3K, and AKT kinase expressions in senescent cells are decreased after vitexin and isovitexin treatment. CONCLUSION: Vitexin and isovitexin may inhibit IIS pathway by occupying adenosine-triphosphate binding site pocket of IGFR, subsequently decreasing IGFR expression, thereby promoting longevity and fitness.

Immunomodulatory activity of Senegalia macrostachya (Reichenb. ex DC.) Kyal. & Boatwr seed polysaccharide fraction through the activation of the MAPK signaling pathway in RAW264.7 macrophages.

Senegalia macrostachya (Reichenb. ex DC.) Kyal. & Boatwr seed (SMS) is a wild legume used as food and medicine in many African countries. In the current study, a novel polysaccharide (SMSP2) was extracted from SMS using hot water and purified with DEAE-52 cellulose. Its structure was characterized, and the immunomodulatory activity and possible molecular mechanism in murine macrophage RAW264.7 were explored. The results revealed that SMSP2 was a uronic acid-rich polysaccharide (51.6%, w/w) with a molecular weight of 52.07 kDa. The neutral sugars were mainly arabinose, xylose, mannose, and galactose at a molar ratio of 1.00 : 0.84 : 0.90 : 0.07. Interestingly, SMSP2 treatment markedly promoted macrophage proliferation and phagocytosis and induced the expression of inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-10. SMSP2-induced macrophage stimulation occurs through the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, macrophage surface complement receptor 3 (CR3) might play an important role in SMSP2-induced macrophage activation. This study revealed that SMSP2 is a potent immunomodulator, which could be used as a functional food and a pharmaceutical adjuvant in treating immune-compromising diseases.

Artemisia selengensis Turcz. leaf extract promotes longevity and stress resistance in Caenorhabditis elegans.

BACKGROUND: Artemisia selengensis Turcz. (AST) is a common edible and medicinal herb possessing extensive biological activities and various health-promoting functions. However, the anti-aging effects of AST have been neglected. This work evaluated the effects of AST leaf extract (ASTE) on stress tolerance and longevity in Caenorhabditis elegans. RESULTS: ASTE treatment enhanced stress resistance and significantly extended the lifespan of C. elegans. Moreover, ASTE prolonged the healthspan by increasing body bending and pharyngeal pumping rates, and by reducing the intestinal lipofuscin level and accumulation of intracellular reactive oxygen species (ROS). Caffeoylquinic acids in ASTE, especially dicaffeoylquinic acids, were the major components responsible for these benefits. The mechanism underlying the anti-aging effect of ASTE occurred by activating insulin/insulin-like growth factor, SIR-2.1 signaling and mitochondrial dysfunction pathways, which in turn induced the activity of the transcription factors DAF-16/FOXO and SKN-1/Nrf2. CONCLUSION: These findings provide direct evidence for the anti-aging effects of AST and reveal its potential on promoting healthy aging. © 2022 Society of Chemical Industry.

Aged Pericarpium Citri Reticulatae 'Chachi' Attenuates Oxidative Damage Induced by tert-Butyl Hydroperoxide (t-BHP) in HepG2 Cells.

This study investigated the protective effects of aged Pericarpium Citri Reticulatae 'Chachi' (PCR-C) on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells. According to HPLC analysis, PCR-C aged 10 years (PCR-C10) had the highest flavonoids content, especially polymethoxyflavones (PMFs), compared with the fresh peel of Citrus reticulata cv. 'Chachiensis' and PCR-C aged 1, 3, and 5 years. Then, flavonoids-rich PCR-C samples and non-flavonoids-rich PCR-C samples (NF) were prepared by extracting and purifying PCR-C of different aging periods, for further cell experiments. Pretreatment with flavonoids-rich PCR-C samples (particularly PCR-C10) considerably reversed t-BHP-induced oxidative damage in HepG2 cells by improving cell viability, increasing SOD activity and GSH levels and reducing the overproduction of ROS and MDA. Correlation analysis further indicated that the accumulation of PMFs, mainly 5,6,7,4'-tetramethoxyflavone and nobiletin, was the main reason that PCR-C10 maintained the redox balance in HepG2 cells. These findings provided direct evidence for the cellular antioxidant activity of aged PCR-C and a guide for PCR-C's classification, authentication and rational use.

Modulation of Gut Microbiota by Lactobacillus casei Fermented Raspberry Juice In Vitro and In Vivo.

The aim of this study was to investigate the modulation of gut microbiota by fermented raspberry juice (FRJ) both in vitro and in vivo. Results showed that total phenolic content and antioxidant activities of FRJ reached the highest after fermentation for 42 h. Seventeen phenolic compounds were contained in FRJ, mainly including ellagic acid (496.64 ± 2.91 µg/g) and anthocyanins (total concentration: 387.93 µg/g). FRJ modulated the gut microbiota into a healthy in vitro status, with increase of valeric and isovaleric acids production. In healthy mice, all FRJ treatments improved the production of acetic, butyric and isovaleric acids as well as the gene expression of ZO-1, Claudin-1, Claudin-4, Ocdudin, E-cadherin and Muc-2. Moreover, variable gut microbial compositions were found among the groups fed diet-supplemented the different doses of FRJ, within low and median doses of FRJ may regulate the microbiota to a healthier state compared to the high dose supplementation. This study indicated that fermentation is a potential way to produce plant-based juices, which could reshape the gut microbiota and improve the host health.

Nanoencapsulation of anthocyanins-loaded ß-lactoglobulin nanoparticles: Characterization, stability, and bioavailability in vitro.

This work aims to investigate the effect of desolvation on the stability and bioavailability of nanoparticles of ß-lactoglobulin (ß-Lg) and anthocyanins (AC) extracted from red raspberry pomace. Interactions between the substrates were also studied using multispectral approaches. ß-Lg-nanoparticles were fabricated via heat treatment at 85 °C for 30 min before initiating the desolvation method at pH 7. This method generated monodisperse particles, nano-scale size of ß-Lg, and AC-ß-Lg ranged from 129.13 to 351.85 nm with square morphology obtained by SEM. The AC extract was encapsulated successfully during desolvation process into ß-Lg-nanoparticles with encapsulation efficiency (EE %) of ~77%. Results also showed that AC (from 1 to 13 × 10-4 M) quenched the fluorescence intensity of de-solvated ß-Lg estimated to be 98%, and a binding among them occurred with a Ka-value of 7.59 × 108 M-1 at 25 °C. Addition of AC also gradually increased the antioxidant activity of ß-Lg-nanoparticles with values of 82.51% at the highest AC-concentration (13 × 10-4 M) loaded on ß-Lg-nanoparticles. AC-loaded ß-Lg nanoparticles was more stable in mouth (pH 6.8), simulated gastric (SG, pH 2), and simulated intestinal (SI, pH 6.9) by showing high retention rate (%) than that of AC unencapsulated. Overall, de-solvated-ß-Lg increased the heat-stability and bioavailability of AC, which could be further utilized in various food and pharmaceutical matrices. These findings recommend that ß-Lg nanoparticles could be appropriated as delivery systems for anthocyanins.