Polysaccharide from Boletus aereus ameliorates DSS-induced colitis in mice by regulating the MANF/MUC2 signaling and gut microbiota.

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions characterized by disruptions in the colonic mucus barrier and gut microbiota. In this study, a novel soluble polysaccharide obtained from Boletus aereus (BAP) through water extraction was examined for its structure. The protective effects of BAP on colitis were investigated using a DSS-induced mice model. BAP was found to promote the expression of intestinal mucosal and tight junction proteins, restore the compromised mucus barrier, and suppress the activation of inflammatory signaling. Moreover, BAP reshape the gut microbiota and had a positive impact on the composition of the gut microbiota by reducing inflammation-related microbes. Additionally, BAP decreased cytokine levels through the MANF-BATF2 signaling pathway. Correlation analysis revealed that MANF was negatively correlated with the DAI and the level of cytokines. Furthermore, the depletion of gut microbiota using antibiotic partially inhabited the effect of BAP on the activation of MANF and Muc2, indicating the role of gut microbiota in its protective effect against colitis. In conclusion, BAP had an obvious activation on MANF under gut inflammation. This provides new insights into the prospective use of BAP as a functional food to enhance intestinal health.

Anti-inflammatory activity of Boletus aereus polysaccharides: Involvement of digestion and gut microbiota fermentation.

Boletus aereus, an edible mushroom, has gained popularity as a medicinal and functional food. This study aimed to investigate the digestive characteristics of B. aereus polysaccharide (BAP) and its effects on gut microbiota. In vitro digestion results indicated partial degradation of BAP. Furthermore, the digested BAP displayed significantly enhanced antioxidant ability. The 16S rRNA sequencing data revealed that BAP positively influenced the abundance of Phascolarctobacterium, Prevotella, and Bifidobacterium in the gut microbiota. Additionally, BAP promoted the production of short-chain fatty acids (SCFAs). Metabolites of BAP utilized by the gut microbiota effectively reduced the concentration of TNF-α, IL-1ß, and NO in an LPS-stimulated RAW 264.7 cell inflammation model. Mantel tests demonstrated a strong correlation among fermentation indicators, gut microbiome composition, SCFAs, and inflammatory cytokines. Overall, this research revealed the underlying digestive and fermentation mechanisms of BAP and provided new insights into the usage of edible mushroom polysaccharides in functional food.

A quinoa peptide protects impaired mucus barriers in colitis mice by inhibiting NF-κB-TRPV1 signaling and regulating the gut microbiota.

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions that lead to the disruption of the colonic mucus barrier. Quinoa has a well-balanced profile of essential amino acids and exhibits excellent anti-inflammatory effects. We recently explored the beneficial effects and relevant mechanisms of a novel quinoa peptide TPGAFF on impaired mucus barriers in mice with chemically induced colitis. Our findings demonstrated that TPGAFF, administered in low and high doses for 28 days, effectively attenuated the pathological phenotype and reduced intestinal permeability in colitis mice. TPGAFF demonstrated its protective abilities by restoring the impaired mucus barrier, inhibiting the activation of inflammatory signaling and reducing inflammatory cytokine levels. Moreover, TPGAFF positively influenced the composition of the gut microbiota by reducing inflammation-related microbes. Additionally, TPGAFF inhibited the activation of TRPV1 nociceptor and decreased the levels of neuropeptides. Conclusively, our results indicated that oral administration of TPGAFF may be an optional approach for the treatment of mucus barrier damage.

Wheat Germ-Derived Peptide Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice.

This study explores the protective properties and potential mechanisms of wheat-germ-derived peptide APEPEPAF (APE) against ulcerative colitis. Colitis mice induced by dextran sulfate sodium (DSS) were used as the animal model. The results showed that the APE peptide could alleviate colitis symptoms including weight loss, colon shortening, and histopathological changes. This peptide attenuated the generation of inflammatory cytokines by inhibiting the phosphorylation of protein kinase PKCζ (Thr410) and NF-κB transcriptional activity in DSS-induced mice, suggesting that APE ameliorates colitis inflammation by regulating the PKCζ/NF-κB signaling pathway. APE also preserved the barrier function of the colon by dose-dependently promoting the expression of tight junction proteins (claudin-1, zonula occluded-1, and occludin). In addition, APE significantly decreased the abundance of Bacteroides and increased the abundance of Dubosiella and Lachnospiraceae_UCG-006 to improve the intestinal flora imbalance in DSS-induced colitis mice. Therefore, wheat germ peptide APE can be used as a novel agent and dietary supplement to treat ulcerative colitis..

Chronotoxicity of Acrylamide in Mice Fed a High-Fat Diet: The Involvement of Liver CYP2E1 Upregulation and Gut Leakage.

Acrylamide (ACR) is produced under high-temperature cooking of carbohydrate-rich foods via the Maillard reaction. It has been reported that ACR has hepatic toxicity and can induce liver circadian disorder. A high fat diet (HFD) could dysregulate liver detoxification. The current study showed that administration of ACR (100 mg/kg) reduced the survival rate in HFD-fed mice, which was more pronounced when treated during the night phase than during the day phase. Furthermore, ACR (25 mg/kg) treatment could cause chronotoxicity in mice fed a high-fat diet, manifested as more severe mitochondrial damage of liver during the night phase than during the day phase. Interestingly, HFD induced a higher CYP2E1 expressions for those treated during the night phase, leading to more severe DNA damage. Meanwhile, the expression of gut tight junction proteins also significantly decreases at night phase, leading to the leakage of LPSs and exacerbating the inflammatory response at night phase. These results indicated that a HFD could induce the chronotoxicity of ACR in mice liver, which may be associated with increases in CYP2E1 expression in the liver and gut leak during the night phase.

Emulsifying properties of wheat germ protein: Effect of different ultrasonic treatment.

The effect of ultrasonic treatment on emulsifying properties of wheat germ protein (WGP) was studied in this paper. WGP was subjected to low frequency (20 kHz), high intensity ultrasonic treatment at different power (200, 400, 600, 800 W) for 10 min, or different time (2, 4, 6, 8, 10, 15, 20 min) at 400 W. The emulsifying activity index and emulsion stability index of WGP were significantly improved, and the emulsion droplet was smaller and more uniform after ultrasound treatment. Ultrasound increased the adsorbed WGP concentration at the oil-water interface and reduced the interfacial tension, which explained the improved emulsifying properties of WGP. The investigation on molecular properties and protein conformation showed that ultrasound processing increased solubility, but decreased particle size and surface charge of WGP. Ultrasound processing resulted in the unfolding of the protein molecular structure indicated by the increase of surface hydrophobicity and surface free sulfhydryl group levels, and the decrease of intrinsic fluorescence intensity. Correlation analysis showed that the changes in WGP solubility, particle size, and surface hydrophobicity were the main driven factors for the improved emulsifying properties of WGP.

A nexus of dietary restriction and gut microbiota: Recent insights into metabolic health.

In recent times, dietary restriction (DR) has received considerable attention for its promising effects on metabolism and longevity. Previous studies on DR have mainly focused on the health benefits produced by different restriction patterns, whereas comprehensive reviews of the role of gut microbiota during DR are limited. In this review, we discuss the effects of caloric restriction, fasting, protein restriction, and amino acid restriction from a microbiome perspective. Furthermore, the underlying mechanisms by which DR affects metabolic health by regulating intestinal homeostasis are summarized. Specifically, we reviewed the impacts of different DRs on specific gut microbiota. Additionally, we put forward the limitations of the current research and suggest the development of personalized microbes-directed DR for different populations and corresponding next-generation sequencing technologies for accurate microbiological analysis. DR effectively modulates the composition of the gut microbiota and microbial metabolites. In particular, DR markedly affects the rhythmic oscillation of microbes which may be related to the circadian clock system. Moreover, increasing evidence supports that DR profoundly improves metabolic syndrome, inflammatory bowel disease, and cognitive impairment. To summarize, DR may be an effective and executable dietary manipulation strategy for maintaining metabolic health, however, further investigation is needed to elucidate the underlying mechanisms.

Advances in Plant Polysaccharides as Antiaging Agents: Effects and Signaling Mechanisms.

Aging refers to the gradual physiological changes that occur in an organism after reaching adulthood, resulting in senescence and a decline in biological functions, ultimately leading to death. Epidemiological evidence shows that aging is a driving factor in the developing of various diseases, including cardiovascular diseases, neurodegenerative diseases, immune system disorders, cancer, and chronic low-grade inflammation. Natural plant polysaccharides have emerged as crucial food components in delaying the aging process. Therefore, it is essential to continuously investigate plant polysaccharides as potential sources of new pharmaceuticals for aging. Modern pharmacological research indicates that plant polysaccharides can exert antiaging effects by scavenging free radicals, increasing telomerase activity, regulating apoptosis, enhancing immunity, inhibiting glycosylation, improving mitochondrial dysfunction regulating gene expression, activating autophagy, and modulating gut microbiota. Moreover, the antiaging activity of plant polysaccharides is mediated by one or more signaling pathways, including IIS, mTOR, Nrf2, NF-κB, Sirtuin, p53, MAPK, and UPR signaling pathways. This review summarizes the antiaging properties of plant polysaccharides and signaling pathways participating in the polysaccharide-regulating aging process. Finally, we discuss the structure-activity relationships of antiaging polysaccharides.

The Impact of Financial Literacy on Household Health Investment: Empirical Evidence from China.

Based on the 2019 China Household Finance Survey (CHFS) data, this paper used factor analysis to measure the level of financial literacy of surveyed householders and used the Probit model and the negative binomial model to test the impact of financial literacy (FL) on household health investment (HHI). The results show that: (1) FL is an essential influencing factor in increasing participation in HHI, and householders with a higher level of FL are also more willing to pay for diversified investments. (2) We split the FL level from the two dimensions of knowledge and ability. We found that the primary FL (including financial knowledge, computing ability, and correct recognition of investment product risk) plays a more critical role in the investment decision process. (3) When information sources, health knowledge, and family income are used as mediating variables, FL can influence the decisions of HHI in three ways: expanding information sources, enriching health knowledge, and alleviating income constraints. (4) By analyzing the heterogeneity of household heads in different regions and with different personal characteristics, we found that the medical level of the household location and the life and work experience of the householders played a moderating role.

Alternate-day fasting prevents non-alcoholic fatty liver disease and working memory impairment in diet-induced obese mice.

Alternate-day fasting (ADF) regimen has been reported to alleviate obesity and insulin resistance. However, the effects of ADF on preventing diet-induced non-alcoholic fatty liver disease (NAFLD) and related cognitive deficits are still elusive. In the present study, a high-fat diet (HFD)-induced obese (DIO) C57BL/6 mouse model was established. Mice were treated with a 4-week long ADF regimen and/or switching the diet to a standard diet. ADF reduced lipid accumulation, activated AMPK/ULK1 signaling, and suppressed the phosphorylation of mTOR. Also, ADF inhibited lipid accumulation and inflammatory responses in the white adipose tissue and down-regulated expressions of PPAR-γ and cytokines. Moreover, ADF improved the working memory and synaptic structure in the DIO mice and upregulated PSD-95 and BDNF in the hippocampus. ADF reduced oxidative stress and microglial over-activation in the CNS. These results suggest that ADF attenuates NAFLD development in the liver of DIO mice, which is related to the mediating effects of ADF on autophagy and energy metabolism. ADF also enhanced cognitive function, which could be partly explained by the down-regulated peripheral inflammatory responses. This study indicates that ADF could be a promising intervention for alleviating NAFLD development and cognitive decline.

A peptide from wheat germ abolishes the senile osteoporosis by regulating OPG/RANKL/RANK/TRAF6 signaling pathway.

BACKGROUND: Oxidative stress played a key role in the development of bone brittleness and is an important pathogenic factor of senile osteoporosis. A variety of animal and plant-derived peptides have been shown to have significant anti-osteoporosis effects in vivo and in vitro. PURPOSE: In this study, we aim to explore the possible mechanism of wheat germ peptide ADWGGPLPH on senile osteoporosis. STUDY DESIGN: Naturally, aged rats were used as animal models of senile osteoporosis. METHODS: Wheat germ peptide ADWGGPLPH was administered from 9-months-old to 21-months-old, and the effect of ADWGGPLPH on preventing senile osteoporosis was evaluated by measuring serum biochemical indexes, bone histomorphometry, bone biomechanics, and other indexes to elucidate the mechanism of ADWGGPLPH in delaying senile osteoporosis by detecting the expression of osteoporosis-related proteins. RESULTS: The results showed that ADWGGPLPH could effectively reduce the level of oxidative stress and improve the microstructure and bone mineral density in senile osteoporosis rats. In addition, ADWGGPLPH could improve the proliferation and differentiation activity of osteoblasts and effectively inhibit osteoclasts' differentiation by regulating the OPG/RANKL/RANK/TRAF6 pathway. CONCLUSION: ADWGGPLPH from wheat germ exhibited a notably effect on senile osteoporosis and has a high potential in the development of the nutrient regimen to against senile osteoporosis.

Isorhamnetin attenuates high-fat and high-fructose diet induced cognitive impairments and neuroinflammation by mediating MAPK and NFκB signaling pathways.

Isorhamnetin (ISO), a flavonoid compound isolated from sea-buckthorn (Hippophae rhamnoides L.) fruit, has anti-inflammatory effects. However, the effects of ISO on neuroinflammation and cognitive function are still unclear. The purpose of this study was to evaluate the protective effect of ISO on cognitive impairment in obese mice induced by a high-fat and high fructose diet (HFFD). It has been found that oral administration of ISO (0.03% w/w and 0.06% w/w) for 14 weeks significantly reduced the body weight, food intake, liver weight, liver lipid level, and serum lipid level of HFFD-fed mice. ISO can also significantly prevent HFFD-induced neuronal working, spatial, and long-term memory impairment. Notably, the ISO treatment activated the CREB/BDNF pathway and increased neurotrophic factors in the brains of mice. Furthermore, ISO inhibited HFFD-induced microglial overactivation and down-regulated inflammatory cytokines in both serum and the brain. It can also inhibit the expression of p-JNK, p-p38, and p-NFκB protein in the mouse brain. In conclusion, these results indicated that ISO mitigated HFFD-induced cognitive impairments by inhibiting the MAPK and NFκB signaling pathways, suggesting that ISO might be a plausible nutritional intervention for metabolic syndrome-related cognitive complications.

Methionine restriction alleviates age-associated cognitive decline via fibroblast growth factor 21.

Methionine restriction (MR) extends lifespan and delays the onset of aging-associated pathologies. However, the effect of MR on age-related cognitive decline remains unclear. Here, we find that a 3-month MR ameliorates working memory, short-term memory, and spatial memory in 15-month-old and 18-month-old mice by preserving synaptic ultrastructure, increasing mitochondrial biogenesis, and reducing the brain MDA level in aged mice hippocampi. Transcriptome data suggest that the receptor of fibroblast growth factor 21 (FGF21)-related gene expressions were altered in the hippocampi of MR-treated aged mice. MR increased FGF21 expression in serum, liver, and brain. Integrative modelling reveals strong correlations among behavioral performance, MR altered nervous structure-related genes, and circulating FGF21 levels. Recombinant FGF21 treatment balanced the cellular redox status, prevented mitochondrial structure damages, and upregulated antioxidant enzymes HO-1 and NQO1 expression by transcriptional activation of Nrf2 in SH-SY5Y cells. Moreover, knockdown of Fgf21 by i.v. injection of adeno-associated virus abolished the neuroprotective effects of MR in aged mice. In conclusion, the MR exhibited the protective effects against age-related behavioral disorders, which could be partly explained by activating circulating FGF21 and promoting mitochondrial biogenesis, and consequently suppressing the neuroinflammation and oxidative damages. These results demonstrate that FGF21 can be used as a potential nutritional factor in dietary restriction-based strategies for improving cognition associated with neurodegeneration disorders.

Methionine Restriction Improves Gut Barrier Function by Reshaping Diurnal Rhythms of Inflammation-Related Microbes in Aged Mice.

Age-related gut barrier dysfunction and dysbiosis of the gut microbiome play crucial roles in human aging. Dietary methionine restriction (MR) has been reported to extend lifespan and reduce the inflammatory response; however, its protective effects on age-related gut barrier dysfunction remain unclear. Accordingly, we focus on the effects of MR on inflammation and gut function. We found a 3-month methionine-restriction reduced inflammatory factors in the serum of aged mice. Moreover, MR reduced gut permeability in aged mice and increased the levels of the tight junction proteins mRNAs, including those of occludin, claudin-1, and zona occludens-1. MR significantly reduced bacterial endotoxin lipopolysaccharide concentration in aged mice serum. By using 16s rRNA sequencing to analyze microbiome diurnal rhythmicity during 24 h, we found MR moderately recovered the cyclical fluctuations of the gut microbiome which was disrupted in aged mice, leading to time-specific enhancement of the abundance of short-chain fatty acid-producing and lifespan-promoting microbes. Moreover, MR dampened the oscillation of inflammation-related TM7-3 and Staphylococcaceae. In conclusion, the effects of MR on the gut barrier were likely related to alleviation of the oscillations of inflammation-related microbes. MR can enable nutritional intervention against age-related gut barrier dysfunction.

Methionine restriction alleviates high-fat diet-induced obesity: Involvement of diurnal metabolism of lipids and bile acids.

Circadian misalignment induced by a high-fat diet (HFD) increases the risk of metabolic diseases. Methionine restriction (MR) is known to have the potential of alleviating obesity by improving insulin sensitivity. However, the role of the circadian clock in mediating the effects of MR on obesity-related metabolic disorders remains unclear. Ten-week-old male C57BL/6 J mice were fed with a low-fat diet (LFD) or a HFD for 4 wk., followed with a full diet (0.86% methionine, w/w) or a methionine-restricted diet (0.17% methionine, w/w) for 8 wk. Our results showed that MR attenuated insulin resistance triggered by HFD, especially at ZT12. Moreover, MR led to a time-specific enhancement of the expression of FGF21 and activated the AMPK/PGC-1α signaling. Notably, MR upregulated the cyclical levels of cholic acid (CA) and chenodeoxycholic acid (CDCA), and downregulated the cyclical level of deoxycholic acid (DCA) in the dark phase. MR restored the HFD-disrupted cyclical fluctuations of lipidolysis genes and BAs synthetic genes and improved the circulating lipid profile. Also, MR improved the expressions of clock-controlled genes (CCGs) in the liver and the brown adipose tissue throughout one day. In conclusion, MR exhibited the lipid-lowering effects on HFD-induced obesity and restored the diurnal metabolism of lipids and BAs, which could be partly explained by improving the expression of CCGs. These findings suggested that MR could be a potential nutritional intervention for attenuating obesity-induced metabolic misalignment.

Methionine Restriction Regulates Cognitive Function in High-Fat Diet-Fed Mice: Roles of Diurnal Rhythms of SCFAs Producing- and Inflammation-Related Microbes.

SCOPE: Methionine restriction (MR) is known to potently alleviate inflammation and improve gut microbiome in obese mice. The gut microbiome exhibits diurnal rhythmicity in composition and function, and this, in turn, drives oscillations in host metabolism. High-fat diet (HFD) strongly altered microbiome diurnal rhythmicity, however, the role of microbiome diurnal rhythmicity in mediating the improvement effects of MR on obesity-related metabolic disorders remains unclear. METHODS AND RESULTS: 10-week-old male C57BL/6J mice are fed a low-fat diet or HFD for 4 weeks, followed with a full diet (0.86% methionine, w/w) or a methionine-restricted diet (0.17% methionine, w/w) for 8 weeks. Analyzing microbiome diurnal rhythmicity at six time points, the results show that HFD disrupts the cyclical fluctuations of the gut microbiome in mice. MR partially restores these cyclical fluctuations, which lead to time-specifically enhance the abundance of short-chain fatty acids producing bacteria, increases the acetate and butyric, and dampens the oscillation of inflammation-related Desulfovibrionales and Staphylococcaceae over the course of 1 day. Notably, MR, which protects against systemic inflammation, influences brain function and synaptic plasticity. CONCLUSION: MR could serve as a potential nutritional intervention for attenuating obesity-induced cognitive impairments by balancing the circadian rhythm in microbiome-gut-brain homeostasis.

Sea-Buckthorn Flavonoids Alleviate High-Fat and High-Fructose Diet-Induced Cognitive Impairment by Inhibiting Insulin Resistance and Neuroinflammation.

Sea-buckthorn flavonoids (SFs) have been used as functional food components for their bioactive potential in preventing metabolic complications caused by diet, such as obesity and inflammation. However, the protective effect of SFs on cognitive functions is not fully clear. In this study, a high-fat and high-fructose diet (HFFD)-induced obese mice model was treated with SFs for 14 weeks. It was found that the oral SF administration (0.06% and 0.31% w/w, mixed in diet) significantly reduced bodyweight gain and insulin resistance in the HFFD-fed mice. SFs significantly prevented HFFD-induced neuronal loss and memory impairment in behavioral tests. Additionally, SFs also suppressed the HFFD-induced synaptic dysfunction and neuronal damages by increasing the protein expressions of PSD-95. Furthermore, SF treatment activated the ERK/CREB/BDNF and IRS-1/AKT pathways and inactivated the NF-κB signaling and its downstream inflammatory mediator expressions. In conclusion, SFs are a potential nutraceutical to prevent high-energy density diet-induced cognitive impairments, which could be possibly explained by their mediating effects on insulin signaling and inflammatory responses in the brain.

Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment.

Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metabolism gene expression in hippocampus, re-structures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are observed between IF affected genes, microbiota and metabolites, as assessed by integrative modelling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metabolism-implicated cognitive pathophysiologies.

Protective Effects of Sesamol on Systemic Inflammation and Cognitive Impairment in Aging Mice.

Sesamol, a lignan in sesame, possesses several bioactivities, such as antioxidation, anti-inflammation, and neuroprotective capability. In this study, the effects of sesamol on aging-caused cognitive defects are investigated. Twelve-month-old mice were treated with sesamol (0.1%, w/w) as dietary supplementation for 12 weeks. Behavioral tests revealed that sesamol improved aging-associated cognitive impairments. Sesamol decreased aging-induced oxidative stress via suppression of malondialdehyde production and increased antioxidant enzymes. Histological staining showed that sesamol treatment improved aging-induced neuronal damage and synaptic dysfunction in the hippocampus. Furthermore, sesamol significantly reduced aging-induced neuroinflammation by inhibiting the microglial overactivation and inflammatory cytokine expressions. Meanwhile, the accumulation of Aß1-42 was reduced by sesamol treatment. Moreover, sesamol protected the gut barrier integrity and reduced LPS release, which was highly associated with its beneficial effects on behavioral and inflammatory changes. In conclusion, our findings indicated that the use of sesamol is feasible in the treatment of aging-related diseases.

Role of Food Phytochemicals in the Modulation of Circadian Clocks.

The circadian clock is an intrinsic mechanism of biological adaptation to the cyclical changes of the environment. The circadian rhythm disorders affect the life activities of organisms. A variety of phytochemicals (e.g., polyphenols, flavonoids, alkaloids, and melatonin) reportedly can regulate the expression and rhythm of circadian clock genes and stabilize the internal environment. This perspective focuses on the relationship of circadian clock genes with oxidative stress, inflammatory response, and metabolic disorders and emphasizes the regulation of phytochemicals on the circadian clock. Potential mechanisms and applications of supplemental phytochemicals to improve metabolic disorders and circadian rhythm disorders are also discussed.