Laminaria Japonica Polysaccharide Improved the Productivities and Systemic Health of Ducks by Mediating the Gut Microbiota and Metabolome.

This study investigated the beneficial effects of a Laminaria japonica polysaccharide (LJPS) on the systemic health of ducks by modulating the gut microbiome and metabolome. Our findings demonstrated that the LJPS supplementation enhanced the overall growth performance and physiological immune and antioxidant index of ducks. In addition, the LJPS-fed group significantly increased abundances of intestinal Bacteroides and Prevotellaceae with decreased α-diversity than that in the control group. Among the total of 1840 intestinal metabolites, 186 metabolites were identified to be differentially regulated by LJPS feeding (upregulated 143 metabolites and downregulated 43 metabolites), which is closely associated with some of the growth-related metabolic pathways. Lastly, the correlation analysis recapitulates that the beneficial effects of LJPS underlie the alterations in intestinal microbiota and metabolites. Taken together, LJPS supplementation improved the physiological parameters and richness of some beneficial microbes and upregulated certain metabolic pathways, which facilitated better productivities and systemic health of ducks.

Influence of the ecological environment on the structural characteristics and bioactivities of polysaccharides from alfalfa (Medicago sativa L.).

Polysaccharides from alfalfa (Medicago sativa L.) (APS) exhibit a variety of bioactivities; however, little information is available on the effects of the ecological environment on the structural characteristics and bioactivities of APS. This study aimed to investigate the structural characteristics and bioactivities of two APS types isolated from alfalfa; these APSs were obtained from alfalfa cultured in normal soil (APS1) or saline-alkali soil (APS2). Results indicated that the two kinds of APS had the same monomer compositions in different molar proportions, where APS2 had greater content of arabinose and galacturonic acid than APS1. Furthermore, APS1 exhibited a greater molar mass of 1.77 × 105 g mol-1 as compared to 1.01 × 105 g mol-1 for APS2. Likewise, APS1 and APS2 had highly branched molecules with crosslinking nets composed of similar monomer residues but with different glycosidic linkages. Additionally, both APS significantly inhibited both adipogenesis and lipid accumulation in 3T3-L1 cells by downregulating mRNA expression of Ppar-γ, C/ebp-α, and Fas; APS2 had superior antiadipogenic effects as compared to APS1. Altogether, the ecological environment impacts the structural characteristics and biofunctions of APS, making them potential candidates for antiadipogenic use through functional food. These findings provide a novel perspective for the selection of phytogenic polysaccharides with specific bioactivities by considering growth environmental conditions.

Diet Type Impacts Production Performance of Fattening Lambs by Manipulating the Ruminal Microbiota and Metabolome.

The pelleted total mixed ration (PTMR) has a positive effect on the productivity of fattening lambs. However, whether the beneficial effects are underpinned by altering the rumen microbiota and metabolome that remain unclear. This study aimed to investigate correlations among growth performance, ruminal microbiota, and ruminal metabolome of lambs fed PTMR diet. A total of 100 crossbred (Dorper sheep × Fine-wool sheep) ram lambs at 55 days of age with similar body weight (BW) (13.2 ± 0.5 kg) were randomly allocated to 10 pens that were fed either PTMR (PTMR group) or unpelleted total mixed ration (UPTMR group) with the same dietary ingredients and nutritional contents. The average daily gain (ADG) and average daily feed intake (ADFI) were determined during the 62-day experimental period and ruminal pH, volatile fatty acid (VFA) concentrations, microbiota, and metabolome in the rumen of the lambs were examined at the end of the experiment. Compared to those of the UPTMR group, the PTMR group had greater ADFI (P = 0.002), ADG (P = 0.003), and feed efficiency (G/F) (P < 0.05). Similarly, feeding PTMR increased the concentration of total VFA (TVFA) and the molar proportion of propionate, but decreased the proportion of butyrate and acetate to propionate ratio in the rumen of lambs compared to that in lambs from the UPTMR group (P < 0.05). In addition, the PTMR group demonstrated lowered alpha-diversity of the ruminal microbiota and enhanced the relative abundance of Fibrobacter (P < 0.05), Veillonellaceae (P < 0.05), and the abundance of Rikenellaceae (P = 0.064) in the rumen compared with those in the UPTMR group. Feeding lambs with PTMR significantly upregulated the metabolic pathways involving tryptophan, histidine, cysteine and methionine, ß-alanine, tyrosine metabolisms, and steroid biosynthesis. Moreover, the abundance of the microbiota strongly correlated with the altered performance, ruminal VFA, metabolites, and metabolic pathways of lambs. Taken together, feeding PTMR shaped the ruminal microbiota of lambs with decreased diversity, while improving relative abundance of some specific microbes and upregulating certain growth-related metabolic pathways, which contributed to the augmented growth performance and G/F of fattening lambs. Thus, feeding PTMR to fattening lambs for superior production performance and G/F is recommended.

Structural Characteristics and Immunomodulatory Effects of a Long-Chain Polysaccharide From Laminaria japonica.

Polysaccharides derived from Laminaria japonica (LJPS) have shown a variety of beneficial effects on improving human health; however, the structural features and bioactivities of long-chain LJPS remain unclear. This study aimed to investigate the structural characteristics and bioactivities of a novel long-chain LJPS. Results showed that the LJPS was composed of Fuc, Rha, Ara, Gal, Glc, Xyl, Man, Fru, Rib, GalA, GluA, GlcA, and ManA, with a molar ratio of 35.71:1.48:0.28:13.16:0.55:2.97:6.92:0.58:0.41:0.14:3.16:15.84:18.79. Of these, Fuc, Gal, Man, GlcA, and ManA were the predominant components with an accumulated proportion of 93.6%. The LJPS was found to consist of seven types of the monomer residues, and the main interchain glycosidic linkages were ß -D-(1 → 2), α -D-(1 → 3), (1 → 4), and (1 → 6), and the molecular mass was 5.79 × 104 g/mol. Regarding the molecular conformation, LJPS was a multi-branched, long-chain macromolecule, and appeared in a denser crosslinking network with highly branched and helix domains in the terms of morphology. Additionally, the LJPS had no toxicity to mouse macrophage cells and exhibited biphasic immuno-modulating capacity. The present findings suggested that the long-chain LJPS might be an attractive candidate as an immunopotentiating and anti-inflammatory functional food, and this study also provides a feasible approach to decipher the structural characteristics and spatial conformations of plant-derived polysaccharides.

Correction: Influence of the ecological environment on the structural characteristics and bioactivities of polysaccharides from alfalfa (Medicago sativa L.).

Correction for 'Influence of the ecological environment on the structural characteristics and bioactivities of polysaccharides from alfalfa (Medicago sativa L.)' by Chongyu Zhang et al., Food Funct., 2022, https://doi.org/10.1039/d2fo00371f.

A functional variant of IC53 correlates with the late onset of colorectal cancer.

The IC53 gene was reported to be upregulated in the colon adenocarcinoma cell line SW480. Here, we show that the expression level of IC53 is positively correlated with the grade and depth of invasion in adenocarcinoma of the colon. Injection of IC53 stably transfected HCT-116 cells into athymic nude mice promoted tumor growth. Furthermore, overexpression of IC53 increased cell invasive growth, which could be dramatically prevented by knocking down IC53 with siRNA. The effects of IC53 on cell-invasive growth were mediated by upregulation of integrins, activation of phosphatidylinositol 3-kinase and phosphorylation of Akt. A single-nucleotide polymorphism rs2737 in the IC53 gene created a potential microRNA379 target site, and microRNA379 expression inhibited IC53 translation. Among 222 patients with colorectal cancer, the C/C rs2737 genotype was associated with late onset of colorectal cancer (median age 63.0 versus 55.3 years, P = 0.003). The frequency of the C/C rs2737 genotype was much lower in patients who developed colorectal cancer below the age of 45 years than in individuals over age 45 years (10.8% versus 26.6%, P = 0.039). These data indicated that IC53 is a positive mediator for colon cancer progression, and IC53-rs2737 may serve as protection from the onset of colorectal cancer.

S100A6 overexpression is associated with poor prognosis and is epigenetically up-regulated in gastric cancer.

S100A6 has been implicated in a variety of biological functions as well as tumorigenesis. In this study, we investigated the expression status of S100A6 in relation to the clinicopathological features and prognosis of patients with gastric cancer and further explored a possible association of its expression with epigenetic regulation. S100A6 expression was remarkably increased in 67.5% of gastric cancer tissues as compared with matched noncancerous tissues. Statistical analysis demonstrated a clear correlation between high S100A6 expression and various clinicopathological features, such as depth of wall invasion, positive lymph node involvement, liver metastasis, vascular invasion, and tumor-node metastasis stage (P < 0.05 in all cases), as well as revealed that S100A6 is an independent prognostic predictor (P = 0.026) significantly related to poor prognosis (P = 0.0004). Further exploration found an inverse relationship between S100A6 expression and the methylation status of the seventh and eighth CpG sites in the promoter/first exon and the second to fifth sites in the second exon/second intron. In addition, the level of histone H3 acetylation was found to be significantly higher in S100A6-expressing cancer cells. After 5-azacytidine or trichostatin A treatment, S100A6 expression was clearly increased in S100A6 low-expressing cells. In conclusion, our results suggested that S100A6 plays an important role in the progression of gastric cancer, affecting patient prognosis, and is up-regulated by epigenetic regulation.

Phospholipase A2 group IIA expression correlates with prolonged survival in gastric cancer.

AIMS: The secreted phospholipase A2 type IIA (PLA2G2A) gene has been identified as a modifier of intestinal adenoma multiplicity in Apc(Min/+) mice. The aim of the present study was to analyse the clinical significance of PLA2G2A expression in human gastric cancer. METHODS AND RESULTS: Using immunohistochemistry, cytoplasmic immunoreactivity of PLA2G2A was observed in 27% (40 of 149) of gastric cancer tissues compared with negative staining in normal mucosa. The PLA2G2A expression rate in well-differentiated carcinoma was elevated significantly compared with that in poorly differentiated carcinoma (46% versus 19%, P = 0.001). Statistical analysis also revealed that PLA2G2A expression correlated negatively with depth of mural invasion, lymph node metastasis and tumour-node-metastasis (TNM) stage (P < 0.05). Patients with positive PLA2G2A expression showed higher 5-year overall survival than those with negative expression (P = 0.0004). In intestinal metaplasia, PLA2G2A was found to be abundant in Paneth cells. The coexistence of PLA2G2A and lysozyme was observed in Paneth cell-rich gastric cancer (P < 0.0001). CONCLUSIONS: PLA2G2A may predict survival and might be a potential biomarker for early detection and individualized therapy.

Potential Antidiabetic Effects of Seaweed Extracts by Upregulating Glucose Utilization and Alleviating Inflammation in C2C12 Myotubes.

Seaweed is known to have various health-promoting effects. However, the mechanisms underlying seaweed's antidiabetic effects remain unclear. We investigated the potential antidiabetic effects of seaweed water extracts and further examined their mechanism(s) using C2C12 mouse skeletal muscle cells. Briefly, we screened the physiochemical properties of seven seaweed extracts by comparing the antioxidant and α-glucosidase inhibitory effects. Among them, three seaweed extracts, Undaria pinnatifida sporophyll (UPS), Codium fragile (CF), and Gracilaria verrucosa (GV), were selected for further testing of their possible antidiabetic effects with underlying mechanisms using C2C12 myotubes. Consistent with the superior α-glucosidase inhibition of the three seaweed extracts, the extracts also enhanced glucose utilization in myotubes compared to the control. The upregulated glucose uptake by the seaweed extracts was reversed by an AMP-activated protein kinase (AMPK) inhibitor, compound C, in the UPS- and CF-treated groups. Furthermore, all three seaweed extracts significantly promoted the phosphorylation of AMPK which was completely blocked by pretreating with compound C. In addition, all three extracts reduced lipopolysaccharide-simulated TNF-α production in C2C12 cells. Our results demonstrated that all three seaweed extracts exhibited antidiabetic properties through not only the inhibition of glucose absorption but also the promotion of glucose utilization. Moreover, the regulation of inflammatory cytokine production by the extracts suggested their potential anti-inflammatory property which might play a critical role in protecting insulin sensitivity in a chronic inflammatory state. Taken together, UPS, CF, and GV are a promising source to modulate the glucose absorption and utilization in muscle cells partially via the AMPK pathway.

The modulatory effects of alfalfa polysaccharide on intestinal microbiota and systemic health of Salmonella serotype (ser.) Enteritidis-challenged broilers.

Salmonella serotype (ser.) Enteritidis infection in broilers is a main foodborne illness that substantially threatens food security. This study aimed to examine the effects of a novel polysaccharide isolated from alfalfa (APS) on the intestinal microbiome and systemic health of S. ser. Enteritidis-infected broilers. The results indicated that broilers receiving the APS-supplemented diet had the improved (P < 0.05) growth performance and gut health than those fed no APS-supplemented diet. Supplementation with APS enhanced (P < 0.05) the richness of gut beneficial microbes such as Bacteroidetes, Barnesiella, Parabacteroides, Butyricimonas, and Prevotellaceae, while decreased (P < 0.05) the abundance of facultative anaerobic bacteria including Proteobacteria, Actinobacteria, Ruminococcaceae, Lachnospiraceae, and Burkholderiaceae in the S. ser. Enteritidis-infected broilers. The Bacteroides and Odoribacter were identified as the two core microbes across all treatments and combined with their syntrophic microbes formed the hub in co-occurrence networks linking microbiome structure to performance of broilers. Taken together, dietary APS supplementation improved the systemic health of broilers by reshaping the intestinal microbiome regardless of whether S. ser. Enteritidis infection was present. Therefore, APS can be employed as a potential functional additives to inhibit the S. ser. Enteritidis and enhance the food safety in poultry farming.

Dietary Energy Level Impacts the Performance of Donkeys by Manipulating the Gut Microbiome and Metabolome.

Considerable evidence suggests that dietary energy levels and gut microbiota are pivotal for animal health and productivity. However, little information exists about the correlations among dietary energy level, performance, and the gut microbiota and metabolome of donkeys. The objective of this study was to investigate the mechanisms by which dietary energy content dictates the growth performance by modulating the intestinal microbiome and metabolome of donkeys. Thirty-six nine-month-old male Dezhou donkeys with similar body weights were randomly assigned to two groups fed low- or high-energy diets (LE or HE). The results showed that donkeys fed HE had increased (p < 0.05) the average daily gain (ADG) and feed efficiency (G/F) compared with those that received LE diet. The gut microbiota in both groups was dominated by the phyla Firmicutes and Bacteroidetes regardless of the dietary energy level. However, feeding HE to donkeys significantly decreased (p < 0.05) the ratio of Firmicutes to Bacteroidetes (F/B). Compared to the LE group, feeding HE specifically increased the abundances of unidentified_Prevotellaceae (p = 0.02) while decreasing the richness of unidentified_Ruminococcaceae (p = 0.05). Compared to the LE group, feeding the HE diet significantly (p < 0.05) upregulated certain metabolic pathways involving the aspartate metabolism and the urea cycle. In addition, the increased bacteria and metabolites in the HE-fed group exhibited a positive correlation with improved growth performance of donkeys. Taken together, feeding the HE diet increased the richness of Prevotellaceae and upregulated growth-related metabolic pathways, which may have contributed to the ameliorated growth performance of donkeys. Thus, it is a recommendable dietary strategy to feed HE diets to fattening donkeys for superior product performance and feed efficiency.

Effects of dietary supplementation with different fermented feeds on performance, nutrient digestibility, and serum biochemical indexes of fattening lambs.

OBJECTIVE: The effects of adding fermented feed to a pelleted total mixed ration (PTMR) on the growth performance of lambs remain unclear. The present study aimed to investigate the feed efficiency and productivity of lambs that were fed PTMR containing fermented soybean meal (FSM) or wheat bran (FWB). METHODS: Sixty 90-d-old hybrid lambs were randomly allocated into 12 pens (5 lambs/pen) that were randomly assigned to 4 dietary treatments (3 pens/treatment) with PTMR (basal diet), 2% FSM, or Lactobacillus- or yeast-FWB (L-FWB or Y-FWB) addition in the basal diet. RESULTS: The findings showed that lambs fed 2% FSM supplemented diet had enhanced (p<0.05) average daily gain (ADG) and carcass yield (p = 0.015), while they had a decreased (p = 0.006) feed conversion ratio compared to that of other three groups. Inclusion of FSM or FWB in PTMR improved (p<0.05) the nutrient digestibility, while it reduced the urea nitrogen content in serum compared to the PTMR group. Additionally, the decreased ratio of N excretion to ADG (p<0.01) was observed with FSM and L-FWB supplementation compared with the PTMR and Y-FWB groups. CONCLUSION: In conclusion, feeding the fermented feed-supplemented diet improved nutrient digestibility and growth performance, and 2% FSM-supplemented diet exhibited superior production-promoting efficiency to lambs.

Peanut sprout rich in p-coumaric acid ameliorates obesity and lipopolysaccharide-induced inflammation and the inhibition of browning in adipocytes via mitochondrial activation.

Obesity is accompanied by adipose tissue inflammation that subsequently reduces thermogenic potential in brown and beige (brown-like) adipocytes. We previously reported that peanut sprout (PS) inhibited triglyceride accumulation via fatty acid oxidation in adipocytes. However, it is unknown whether PS reverses diet-induced obesity/inflammation and protects against the inflammation-induced inhibition of browning. To investigate this, C57BL/6 male mice, as an in vivo model, were randomly assigned to three different diets and fed for 8 weeks: (i) low-fat diet (LF, 11% kcal from fat), (ii) high-fat diet (HF, 61% kcal from fat), or (iii) HF diet with PS (4% PS in diet, HF + PS). As an in vitro model, lipopolysaccharides (LPS)-induced macrophages and 3T3-L1 adipocytes in the absence (white adipocytes) or presence of dibutyryl-cAMP (Bt-cAMP, beige adipocytes) were used. The supplementation of PS improved HF-diet-mediated body weight gain, dyslipidemia, and hyperglycemia as compared to the HF group. Although there was a marginal impact on visceral hypertrophy, PS reversed the adipocyte inflammation. In parallel, LPS-mediated induction of inflammation was impeded by PS extract (PSE) in macrophages and adipocytes. PSE also protected against LPS-induced suppression of adipocyte browning in Bt-cAMP-treated adipocytes with mitochondrial activation. The phenolic acid analysis showed that among the constituent of PSE, p-coumaric acid (PCA) was identified as a polyphenol that showed a similar effect to PSE. PCA treatment was also able to maintain a higher temperature than the control group upon cold exposure. Taken together, PCA-enriched PS attenuated HF-diet-induced obesity and protected against LPS-induced inflammation and the inhibition of browning via mitochondrial activation.

Pelleting of a Total Mixed Ration Affects Growth Performance of Fattening Lambs.

Feeding pelleted total mixed rations (TMR) instead of traditional loose concentrate plus forage to fattening lambs is an emerging practice. This study aimed to determine the effects of feeding pelleted TMR to fattening lambs on feed intake behaviour, growth performance, feed digestion, rumen fermentation characteristics, rumen microbial community, serum parameters, slaughter performance, meat quality, and the economic outcome. Two physical forms (pelleted vs. un-pelleted) of TMR composed of the same ingredients with the same particle sizes were compared in three animal experiments. Feed intake and average daily gain were higher when the TMR was pelleted, but apparent total tract digestibility of nutrients (organic matter, crude protein, neutral detergent fibre, acid detergent fibre, and ether extract) and serum parameters were not affected and apparent total tract dry matter digestibility was slightly lower. Feeding pelleted TMR increased total short-chain fatty acid concentration and decreased rumen pH. Rumen microbial community was not affected by the physical form of the TMR at phylum level but changed slightly at genus level. Liveweight at slaughter and hot carcass weight were higher for lambs fed the pelleted compared to the un-pelleted TMR, while dressing percentage and meat quality were not affected. In conclusion, feeding pelleted TMR improves growth performance of fattening lambs mainly due to an increase in feed intake. Feeding pelleted TMR is a feasible strategy for intensive lamb fattening operations.

Overexpression of endothelial cell specific molecule-1 (ESM-1) in gastric cancer.

BACKGROUND: The endothelial cell-specific molecule-1 (ESM-1) gene is involved in various biological events. This study was designed to clarify its clinical significance and explore its biological behavior in gastric cancer (GC). METHODS: ESM-1 mRNA expression was evaluated by real-time PCR in GC (n = 34) and matched adjacent normal tissues (n = 14). The expression of ESM-1 protein was investigated by immunohistochemistry in GC (n = 159) and matched normal tissues (n = 40), and its correlation with the clinicopathological features and overall survival of patients was analyzed. Microvessel density (MVD) in GC was assessed by anti-CD34 and the pattern of ESM-1 expression in tumor-related vascular was evaluated. The effect of ESM-1 promotion of proliferation in the GC MKN28 cell line and human microvascular endothelial cell line HMEC-1 were tested using the MTT assay. RESULTS: ESM-1 mRNA was significantly overexpressed in GC compared with adjacent noncarcinoma controls (P < 0.01). ESM-1 protein was predominantly expressed in GC. ESM-1 expression was associated with distant metastasis and Borrmann type IV (P < 0.05) and was strongly associated with vascular invasion (P = 0.0057). Patients with ESM-1 expression showed lower 5-year survival rate (P = 0.0339). Multivariate analysis revealed that ESM-1 was an independent prognostic factor. In GC, CD34-MVD of GC vessels positively expressing ESM-1 was higher than that of GC with negative vessels expression of ESM-1 (P < 0.05). Besides, ESM-1 antibody dose-dependently impaired MKN28 and HMEC-1 growth. CONCLUSIONS: ESM-1 is overexpressed in GC and can serve as a tumor biomarker to predict survival of GC patients, and it might promote tumor angiogenesis and growth in GC and, hence, may represent a potential therapeutic target.

A polysaccharide extracted from alfalfa activates splenic B cells by TLR4 and acts primarily via the MAPK/p38 pathway.

Alfalfa polysaccharide (APS) has been proposed to exhibit growth-promoting and immune-enhancing bodily functions in vivo. However, little is known about its downstream immunomodulatory and intrinsic molecular mechanisms. Herein, mouse splenic lymphocytes were isolated to characterize the immunomodulatory effects and molecular mechanisms of APS in vitro. The results demonstrated that APS selectively improved the cell viability and IgM production of B cells, but no effects on T cell viability or secretion of IL-2, IL-4 and IFN-γ were observed in vitro. The receptor blocking assay showed that TLR4 was the primary receptor involved in APS-mediated B cell activation, which was confirmed by the results obtained using C57BL/10ScNJ (TLR4 gene-deficient) mice. Moreover, APS activated the TLR4-MyD88 signaling pathway at the translational level by significantly increasing the protein expression of TLR4 and MyD88. Downstream pathway blocking assay demonstrated that both the MAPK and NF-κB pathways were involved in APS-induced B cell activation. Additionally, APS significantly enhanced the phosphorylation of p38, ERK, and JNK and activated the nuclear translocation of the NF-κB p65 subunit. Therefore, we concluded that APS specifically activates the immune functions of splenic B cells by TLR4, acting through the MAPK and NF-κB signaling pathways, and potently activates the p38 pathway.

Hypotriglyceridemic effects of brown seaweed consumption via regulation of bile acid excretion and hepatic lipogenesis in high fat diet-induced obese mice.

BACKGROUND/OBJECTIVES: The present study aimed to further investigate the potential health beneficial effects of long-term seaweed supplementation on lipid metabolism and hepatic functions in DIO mice. MATERIALS/METHODS: Four brown seaweeds (Undaria pinnatifida [UP], Laminaria japonica [LJ], Sargassum fulvellum [SF], or Hizikia fusiforme [HF]) were added to a high fat diet (HFD) at a 5% ratio and supplemented to C57BL/6N mice for 16 weeks. Triglycerides (TGs) and total cholesterol (TC) in the liver, feces, and plasma were measured. Fecal bile acid (BA) levels in feces were monitored. Hepatic insulin signaling- and lipogenesis-related proteins were evaluated by Western blot analysis. RESULTS: Fasting blood glucose levels were significantly reduced in the LJ, SF, and HF groups compared to the HFD group by the end of 16-week feeding period. Plasma TG levels and hepatic lipid accumulation were significantly reduced in all 4 seaweed supplemented groups, whereas plasma TC levels were only suppressed in the UP and HF groups compared to the HFD group. Fecal BA levels were significantly elevated by UP, LJ, and SF supplementation compared to HFD feeding only. Lastly, regarding hepatic insulin signaling-related proteins, phosphorylation of 5'-AMP-activated protein kinase was significantly up-regulated by all 4 types of seaweed, whereas phosphorylation of protein kinase B was up-regulated only in the SF and HF groups. Lipogenesis-related proteins in the liver were effectively down-regulated by HF supplementation in DIO mice. CONCLUSIONS: Brown seaweed consumption showed hypotriglyceridemic effects in the prolonged DIO mouse model. Specifically, combinatory regulation of BA excretion and lipogenesis-related proteins in the liver by seaweed supplementation contributed to the reduction of plasma and hepatic TG levels, which inhibited hyperglycemia in DIO mice. Thus, the discrepant and species-specific functions of brown seaweeds provide novel insights for the selection of future targets for therapeutic agents.

Laminaria japonica Extract Enhances Intestinal Barrier Function by Altering Inflammatory Response and Tight Junction-Related Protein in Lipopolysaccharide-Stimulated Caco-2 Cells.

In the normal physiological state, intestinal epithelial cells act as a defensive frontline of host mucosal immunity to tolerate constant exposure to external stimuli. In this study, we investigated the potential anti-inflammatory and gut permeability protective effects of Laminaria japonica (LJ) water extract (LJE) and three types of fermented Laminaria japonica water extracts (LJE-F1, LJE-F2, and LJE-F3) in lipopolysaccharide (LPS)-stimulated Caco-2, human intestinal epithelial cells. All four extracts significantly decreased the production of nitric oxide and interleukin-6 induced by LPS stimulus. In addition, LJE and the three types of LJE-Fs also inhibited LPS-induced loss of monolayer permeability, as assessed by changes in transepithelial electrical resistance. All four LJ extracts significantly prevented the inhibition of the protein levels of occludin, whereas LJE, LJE-F1, and LJE-F3 significantly attenuated the reduction in phosphorylation of adenosine monophosphate-activated protein kinase compared with the LPS-treated group in Caco-2 cells. In conclusion, LJE and its fermented water extracts appear to have potential gut health-promoting effects by reducing inflammation and partially regulating the tight junction-related proteins in human intestinal epithelial cells. Thus, additional studies are warranted to evaluate Laminaria japonica as a therapeutic agent for inflammatory bowel diseases.

Immunomodulatory, antioxidant and intestinal morphology-regulating activities of alfalfa polysaccharides in mice.

The effects of alfalfa polysaccharides (APS) on immunomodulatory and antioxidant functions, as well as intestinal morphology were investigated in vivo in this study. Sixty-four mice were randomly divided into four groups and administered 0, 200, 400 or 800 mg/kg/d body weight APS via gavage for 28 days. The blood parameters and metabolites, viscera indices, antioxidant enzyme activities and intestinal morphology were measured. The results showed that the oral administration of APS improved the immune functions of mice, significantly enhanced the white blood cells and lymphocyte counts, and led to improvements in spleen and thymus indices. APS exhibited significant antioxidant activity by enhancing total antioxidant capacity, superoxide dismutase and glutathione peroxidase activities in heart, kidney and liver, and decreasing the malondialdehyde levels of heart and liver. Moreover, administration of APS potently enhanced the small intestinal villous height and the villus-to-crypt ratio, and decreased the crypt depth of duodenum in mice. Therefore, we can conclude that APS possesses pronounced immunomodulatory activities, and plays an important role in the prevention of oxidative stresses and in the improvement of intestinal morphology in the immunological system in vivo. APS thus shows potential for the development as an effective natural immunomodulatory and antioxidant agent.

Alfalfa polysaccharide prevents H2O2-induced oxidative damage in MEFs by activating MAPK/Nrf2 signaling pathways and suppressing NF-κB signaling pathways.

Alfalfa polysaccharide (APS) is a bioactive component extracted from alfalfa that exhibits potent antioxidant properties. However, the cellular and molecular mechanisms underlying these properties remain unclear. To explore the molecular mechanism by which APS exerts antioxidant effects, an H2O2-induced oxidative stress mouse embryonic fibroblast (MEF) model was established. Cell proliferation, antioxidant enzyme activity, immune cytokine expression, and related protein expression were examined in APS-supplemented or non-supplemented conditions. The results suggested that APS strengthened the antioxidative capacity of MEFs, increasing cell proliferation, superoxide dismutase activity (SOD), and the total antioxidant capacity (T-AOC). In addition, APS reduced the secretion of interleukin (IL)-6 and IL-8 as well as expression of the proinflammatory gene retinoic acid-inducible gene I (RIG-I). APS was also able to activate the mitogen-activated protein kinase (MAPK) pathway, which promoted the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus. However, expression of nuclear factor-κB (NF-κB) was decreased after APS treatment. Overall, these results suggest that APS relieves H2O2-induced oxidative stress in MEFs by activating MAPK/Nrf2 signaling and suppressing NF-κB signaling. To the best of our knowledge, this is the first study to link APS with MAPK/Nrf2, NF-κB and RIG-I, thus providing new perspectives regarding the mechanisms of the antioxidant activity of APS.