Prevotella copri exhausts intrinsic indole-3-pyruvic acid in the host to promote breast cancer progression: inactivation of AMPK via UHRF1-mediated negative regulation.

Emerging evidence has revealed the novel role of gut microbiota in the development of cancer. The characteristics of function and composition in the gut microbiota of patients with breast cancer patients has been reported, however the detailed causation between gut microbiota and breast cancer remains uncertain. In the present study, 16S rRNA sequencing revealed that Prevotella, particularly the dominant species Prevotella copri, is significantly enriched and prevalent in gut microbiota of breast cancer patients. Prior-oral administration of P. copri could promote breast cancer growth in specific pathogen-free mice and germ-free mice, accompanied with sharp reduction of indole-3-pyruvic acid (IPyA). Mechanistically, the present of excessive P. copri consumed a large amount of tryptophan (Trp), thus hampering the physiological accumulation of IPyA in the host. Our results revealed that IPyA is an intrinsic anti-cancer reagent in the host at physiological level. Briefly, IPyA directly suppressed the transcription of UHRF1, following by the declined UHRF1 and PP2A C in nucleus, thus inhibiting the phosphorylation of AMPK, which is just opposite to the cancer promoting effect of P. copri. Therefore, the exhaustion of IPyA by excessive P. copri strengthens the UHRF1-mediated negative control to inactivated the energy-controlling AMPK signaling pathway to promote tumor growth, which was indicated by the alternation in pattern of protein expression and DNA methylation. Our findings, for the first time, highlighted P. copri as a risk factor for the progression of breast cancer.

Selective impact of three homogenous polysaccharides with different structural characteristics from Grifola frondosa on human gut microbial composition and the structure-activity relationship.

Natural polysaccharides interact with gut microbes to enhance human well-being. Grifola frondosa is a polysaccharides-rich edible and medicinal mushroom. The prebiotic potential of G. frondosa polysaccharides has been explored in recent years, however, the relationship between their various structural features and prebiotic activities is poorly understood. In this study, three homogenous polysaccharides GFP10, GFP21 and GFP22 having different molecular weights (Mw), monosaccharide compositions and glycosidic linkages were purified from G. frondosa, and their effects on intestinal microbial composition were compared. GFP10 was a fucomannogalactan with an Mw of 23.0 kDa, and it selectively inhibited Enterobacter, while GFP21 was a fucomannogalactoglucan with an Mw of 18.6 kDa, and it stimulated Catenibacterium. GFP22 was a 4.9 kDa mannoglucan that selectively inhibited Klebsiella and boosted Bifidobacterium, Catenibacterium and Phascolarctobacterium, and prominently promoted the production of short-chain fatty acids (SCFAs). The selective modulation of gut microbiota by polysaccharides was structure-dependent. A relatively lower Mw and a high proportion of glycosidic linkages like T-Glcp, 1,3-Glcp, 1,3,6-Glcp and 1,4-Glcp might be more easily utilized to produce SCFAs and beneficial for the proliferation of Catenibacterium and Phascolarctobacterium. This research provided a valuable resource for further exploring the structure-activity relationship and prebiotic activity of G. frondosa polysaccharides.

Exome-Based Amino Acid Optimization: A Dietary Strategy to Satisfy Human Nutritional Demands and Enhance Muscle Strength in Breast Tumor Mice Undergoing Chemotherapy.

Breast cancer patients undergoing chemotherapy often experience muscle wasting and weakness, which impact their quality of life. A potential solution lies in customizing amino acid compositions based on exome-derived formulations (ExAAs). The study hypothesized that tailoring dietary amino acids using ExAAs could enhance muscle health. Theoretical amino acid requirements were calculated from the genome's exome region, and a breast cancer mouse model undergoing paclitaxel treatment was established. The mice were supplemented with a cancer-specific nutritional formula (QJS), and the effects of QJS and amino acid-adjusted QJS (adjQJS) were compared. Both formulations improved the nutritional status without compromising tumor growth. Notably, adjQJS significantly enhanced muscle strength compared to QJS (1.51 ± 0.25 vs. 1.30 ± 0.08 fold change, p < 0.05). Transcriptome analysis revealed alterations in complement and coagulation cascades, with an observed upregulation of C3 gene expression in adjQJS. Immune regulation also changed, showing a decrease in B cells and an increase in monocytes in skeletal muscle with adjQJS. Importantly, adjQJS resulted in a notable increase in Alistipes abundance compared to QJS (10.19 ± 0.04% vs. 5.03 ± 1.75%). This study highlights the potential of ExAAs as valuable guide for optimizing amino acid composition in diets for breast cancer patients undergoing chemotherapy.

Polysaccharide isolated from Grifola frondosa eliminates myeloid-derived suppressor cells and inhibits tumor growth by enhancing T cells responses.

Myeloid derived suppressor cells (MDSCs) are known to accumulate in cancer patients and tumor-bearing mice, playing a significant role in promoting tumor growth. Depleting MDSCs has emerged as a potential therapeutic strategy for cancer. Here, we demonstrated that a fungal polysaccharide, extracted from Grifola frondosa, can effectively suppress breast tumorigenesis in mice by reducing the accumulation of MDSCs. Treatment with Grifola frondosa polysaccharide (GFI) leads to a substantial decrease in MDSCs in the blood and tumor tissue, and a potent inhibition of tumor growth. GFI treatment significantly reduces the number and proportion of MDSCs in the spleen, although this effect is not observed in the bone marrow. Further analysis reveals that GFI treatment primarily targets PMN-MDSCs, sparing M-MDSCs. Our research also highlights that GFI treatment has the dual effect of restoring and activating CD8+T cells, achieved through the downregulation of TIGIT expression and the upregulation of Granzyme B. Taken together, our findings suggest that GFI treatment effectively eliminates PMN-MDSCs in the spleen, leading to a reduction in MDSC numbers in circulation and tumor tissues, ultimately enhancing the antitumor immune response of CD8+T cells and inhibiting tumor growth. This study introduces a promising therapeutic agent for breast cancer.

Impacts of selenium enrichment on nutritive value and obesity prevention of Cordyceps militaris: A nutritional, secondary metabolite, and network pharmacological analysis.

This study aimed to compare the nutritive value and obesity prevention of ordinary Cordyceps militaris (CM) and selenium-enriched CM (SeCM). The results indicated that Se enrichment significantly increased the total carbohydrate and soluble dietary fiber content, while the protein and insoluble dietary fiber content decreased. Although the fat content was not affected, the medium and long-chain fatty acids content significantly changed. Moreover, Se enrichment significantly elevated the secondary metabolites belonging to terpenoids and alkaloids, which are linked with the enhanced biosynthesis of secondary metabolites. Both CM and SeCM reduced body weight, adipose accumulation, impaired glucose tolerance, and lipid levels in high-fat diet (HFD)-fed mice, and there was no significant difference between them. Network pharmacological analysis revealed that dietary CM and SeCM prevented HFD-induced obesity and associated metabolic diseases with multi-ingredients acting on multi-targets. Overall, Se enrichment improved the nutritive value of CM without altering its role in preventing obesity.

Comparison of Neuroprotection and Regulating Properties on Gut Microbiota between Selenopeptide Val-Pro-Arg-Lys-Leu-SeMet and Its Native Peptide Val-Pro-Arg-Lys-Leu-Met In Vitro and In Vivo.

Selenopeptides are promising candidates for intervening in neuroinflammation; however, the key role of selenium (Se) in selenopeptides remains poorly understood. To address this gap, we compared the neuroprotective effects of selenopeptide Val-Pro-Arg-Lys-Leu-SeMet (namely, Se-P1) and its native peptide Val-Pro-Arg-Lys-Leu-Met (namely, P1). Our results demonstrate that Se-P1 treatment exhibits superior antioxidant and antineuroinflammatory effects in PC12 cells and lipopolysaccharide (LPS)-injured mice compared to P1. Moreover, the administration of Se-P1 and P1 resulted in a shift in the gut microbiota composition. Notably, during LPS-induced injury, Se-P1 treatment demonstrated greater stability in maintaining gut microbiota composition compared to P1 treatment. Specifically, Se-P1 may have a positive impact on gut microbiota dysbiosis by modulating inflammatory-related bacteria such as enhancing Lactobacillus abundance while reducing that of Lachnospiraceae_NK4A136_group. Furthermore, the alteration of metabolites induced by Se-P1 treatment exhibited a significant correlation with gut microbiota, subsequently modulating the inflammatory-related metabolic pathways including histidine metabolism, lysine degradation, and purine metabolism. These findings suggest that organic Se contributes to the bioactivities of Se-P1 in mitigating neuroinflammation in LPS-injured mice compared to P1. These findings hold significant value for the development of potential preventive or therapeutic strategies against neurodegenerative diseases and introduce novel concepts in selenopeptide nutrition and supplementation recommendations.

Comparative proteomic analysis of two divergent strains provides insights into thermotolerance mechanisms of Ganoderma lingzhi.

Heat stress (HS) is a major abiotic factor influencing fungal growth and metabolism. However, the genetic basis of thermotolerance in Ganoderma lingzhi (G. lingzhi) remains largely unknown. In this study, we investigated the thermotolerance capacities of 21 G. lingzhi strains and screened the thermo-tolerant (S566) and heat-sensitive (Z381) strains. The mycelia of S566 and Z381 were collected and subjected to a tandem mass tag (TMT)-based proteome assay. We identified 1493 differentially expressed proteins (DEPs), with 376 and 395 DEPs specific to the heat-tolerant and heat-susceptible genotypes, respectively. In the heat-tolerant genotype, upregulated proteins were linked to stimulus regulation and response. Proteins related to oxidative phosphorylation, glycosylphosphatidylinositol-anchor biosynthesis, and cell wall macromolecule metabolism were downregulated in susceptible genotypes. After HS, the mycelial growth of the heat-sensitive Z381 strain was inhibited, and mitochondrial cristae and cell wall integrity of this strain were severely impaired, suggesting that HS may inhibit mycelial growth of Z381 by damaging the cell wall and mitochondrial structure. Furthermore, thermotolerance-related regulatory pathways were explored by analyzing the protein-protein interaction network of DEPs considered to participate in the controlling the thermotolerance capacity. This study provides insights into G. lingzhi thermotolerance mechanisms and a basis for breeding a thermotolerant germplasm bank for G. lingzhi and other fungi.

A Ganoderma lucidum polysaccharide F31 alleviates hyperglycemia through kidney protection and adipocyte apoptosis.

In this paper, we reported an excellent hypoglycemic effect of a Ganoderma lucidium polysaccharide F31 with efficacies between 45 and 54 %, approaching to that of liraglutide (52 %). Significantly, F31 reduced the body weight gains and food intakes. F31 decreased 4 key compounds, consisting of adenosine, adenosine, galactitol and glycerophosphocholine and elevated 8 key compounds, including arginine, proline, arachidonic acid, creatine, aspartic acid, leucine, phenylalanine and ornithine, which protected kidney function. Also, apoptosis was promoted by F31 in epididymal fat through increasing Caspase-3, Caspase-6 and Bax and decreasing Bcl-2. On 3 T3-L1 preadipocyte cells, F31 induced early apoptosis through reducing mitochondrial membrane potential. Finally, a molecular docking was performed to reveal a plausible cross-talk between kidney and epididymal fat through glycerophosphorylcholine-Bax axis. Overall, F31 alleviated hyperglycemia through kidney protection and adipocyte apoptosis in db/db mice. This work may provide novel insights into the hypoglycemic activity of polysaccharides.

Grifolamine A, a novel bis-γ-butyrolactone from Grifola frondosa exerted inhibitory effect on α-glucosidase and their binding interaction: Affinity and molecular dynamics simulation.

A novel bis-γ-butyrolactone grifolamine A (1), the first γ-butyrolactone dimer from nature, together with three known γ-butyrolactones (2-4), was isolated from the byproduct from Grifola frondosa polysaccharides preparation process. The structure and stereochemistry of grifolamine A (1) were elucidated by extensive spectroscopic analysis combined with quantum chemical calculation. The biosynthetic origin of compound 1, as well as 2-4 was proposed. Grifolamine A (1) showed an intense inhibition against α-glucosidase in vitro. The underlying inhibitory mechanism was revealed by surface plasmon resonance (SPR), molecular docking, molecular dynamics (MD) simulation and binding free energy calculation. SPR revealed that grifolamine A exhibited a strong affinity to α-glucosidase with an equilibrium dissociation constant (KD) value of 1.178 × 10-4 M. Molecular docking manifested that grifolamine A sat at the active pocket of α-glucosidase by van der Waals force, alkyl interaction and carbon hydrogen bonds, and consequently changed the micro-environmental structure of α-glucosidase. MD simulation revealed that grifolamine A had high binding affinity to α-glucosidase with average free energy of -25.2 ± 3.2 kcal/mol. Free energy decomposition indicated amino acid residues including PHE298, PHE308, PHE309, PHE155 and ARG310 at the binding pocket played a strongly positive effect on the interaction between grifolamine A and α-glucosidase. Our findings provide valuable information for the design and development of novel α-glucosidase inhibitors based on γ-butyrolactone skeleton.

Identification of Long Non-Coding RNAs and Their Target Genes from Mycelium and Primordium in Model Mushroom Schizophyllum commune.

Schizophyllum commune has emerged as the most promising model mushroom to study developmental stages (mycelium, primordium), which are two primary processes of fruit body development. Long non-coding RNA (lncRNA) has been proved to participate in fruit development and sex differentiation in fungi. However, potential lncRNAs have not been identified in S. commune from mycelium to primordium developmental stages. In this study, lncRNA-seq was performed in S. commune and 61.56 Gb clean data were generated from mycelium and primordium developmental stages. Furthermore, 191 lncRNAs had been obtained and a total of 49 lncRNAs were classified as differently expressed lncRNAs. Additionally, 26 up-regulated differently expressed lncRNAs and 23 down-regulated between mycelium and primordia libraries were detected. Further, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed lncRNAs target genes from the MAPK pathway, phosphatidylinositol signal, ubiquitin-mediated proteolysis, autophagy, and cell cycle. This study provides a new resource for further research on the relationship between lncRNA and two developmental stages (mycelium, primordium) in S. commune.

Whole-Genome Sequencing and Transcriptome Analysis of Ganoderma lucidum Strain Yw-1-5 Provides New Insights into the Enhanced Effect of Tween80 on Exopolysaccharide Production.

Ganoderma lucidum is an important medicinal mushroom widely cultured in Asian countries. Exopolysaccharides are bioactive compounds of G. lucidum with health benefits. Limited exopolysaccharide content hinders its extraction from G. lucidum. The addition of Tween80 had an enhanced effect on G. lucidum exopolysaccharide production in submerged fermentation. However, the mechanism of this effect remains unclear. In this study, we report on a high-quality assembly of G. lucidum strain yw-1-5 to lay the foundation for further transcriptome analysis. The genome sequence was 58.16 Mb and consisted of 58 scaffolds with an N50 of 4.78 Mb. A total of 13,957 protein-coding genes were annotated and Hi-C data mapped to 12 pseudo-chromosomes. Genes encoding glycosyltransferases and glycoside hydrolases were also obtained. Furthermore, RNA-seq was performed in a Tween80-treated group and control group for revealing the enhanced effect of Tween80 on exopolysaccharide production. In total, 655 genes were identified as differentially expressed, including 341 up-regulated and 314 down-regulated. Further analysis of differentially expressed genes showed that groups of MAPK, amino sugar and nucleotide sugar metabolism, autophagy, ubiquitin-mediated proteolysis, peroxisome, starch and sucrose metabolism, TCA cycle, glycolysis/gluconeogenesis KEGG pathway, glycosyltransferases and glycoside hydrolases played important roles in the enhanced effect of Tween80 on exopolysaccharide production. This work provides a valuable resource for facilitating our understanding of the synthesis of polysaccharides and accelerating the breeding of new strains with a high content of exopolysaccharides.

Transcriptomic analysis of the anti-inflammatory effect of Cordyceps militaris extract on acute gouty arthritis.

Background: Gouty arthritis (GA) is a common inflammatory disease that causes pain due to the deposition of monosodium urate (MSU) crystals into joints and surrounding tissues. Anti-inflammatory drugs have significant clinical anti-inflammatory and analgesic effects, but they have many side effects. Cordyceps militaris is an edible and medicinal fungus, and its extract (CME) has good anti-inflammatory and analgesic effects. This study aimed to investigate the anti-inflammatory effect of CME on GA and its underlying mechanism. Methods: The effect of CME on the expression of related inflammatory factors and histopathological changes in the MSU-induced acute inflammatory gout model in rats was studied by ELISA and HE, and its anti-inflammatory mechanism was analyzed by transcriptome combined with RT-qPCR. Results: CME significantly improved gait scores and joint swelling in GA rats, and reduced MSU-induced inflammatory cell infiltration. CME inhibited MSU-induced inflammatory responses by reducing the levels of pro-inflammatory factors TNF-α, IL-1ß, IL-6, and Caspase-1 and increasing the anti-inflammatory factor IL-10. Transcriptome analysis showed that CME significantly altered inflammation-related cytokine pathways, and identified four major genes involved in regulation of inflammation, CCL7, CSF2RB, LIF, and IL-1ß. In addition, RT-qPCR was performed to verify these differential genes. Conclusion: CME significantly alleviated the inflammatory progression of GA and ameliorated the onset of GA. The underlying mechanism may be related to triggering the cytokine-cytokine receptor interaction signaling pathway to inhibit the activation of the inflammasome and regulate the immune system. And it regulates the inflammatory response induced by MSU crystals through the genes CCL7, CSF2RB, and IL-1ß.

Improvement of extraction from Hericium erinaceus on the gut-brain axis in AD-like mice.

In this study, results showed the extractions of Hericium erinaceus can ameliorate the learning and memory abilities significantly, reduce the swelling of brain tissues, neuronal apoptosis, and down-regulate the expression of Alzheimer's disease intracellular markers including Tau and Aß1-42. 16S rRNA sequencing of gut microbiota indicated that the extractions maintained the diversity and stability of the microbial community, rebalanced the ratio of Firmicutes/Proteobacteria, increased the abundance of some probiotics such as Lactobacillus and Akkermansia, and reduced some pathogenic bacteria and opportunistic pathogenic bacteria such as Enterobacteriaceae. In addition, Akkermanisa, Blautia, Oscillospira, Dehalobacterium, Ackermansia, Allobaculum and Coprococcus were up-regulated, and these bacteria have the effect of anti-intestinal inflammation.Some genera with inhibitory effects on inflammation, such as Desulfovibrio, Alistipes and Rikenellaceae, were down-regulated. Deep studies showed that multi-target compounds from Hericium erinaceus could target the gut microbiota, regulate the metabolism, inflammation, immunity and insulin to slow the progression of Alzheimer's disease. The results suggested that extractions from Hericium erinaceus could be formulated as dietary supplement or/and drug treatments against Alzheimer's disease. However, these pharmacologically active ingredients and mode of action require clinical studies.

An active ingredient isolated from Ganoderma lucidum promotes burn wound healing via TRPV1/SMAD signaling.

The mushroom Ganoderma lucidum is a traditional Chinese medicine and G. lucidum spore oil (GLSO) is the lipid fraction isolated from Ganoderma spores. We examined the effect of GLSO on burn wound healing in mice. Following wounding, GLSO was applied on the wounds twice daily. Repair analysis was performed by Sirius-Red-staining at different time points. Cell proliferation and migration assays were performed to verify the effect of GLSO on growth. Network pharmacology analysis to identify possible targets was also carried out, followed by Western blotting, nuclear translocation, cell proliferation, and immunofluorescence assays for in-depth investigation of the mechanism. Our study showed that GLSO significantly promoted cell proliferation, and network pharmacology analysis suggested that GLSO might act through transient receptor potential vanilloid receptor 1 (TRPV1)/SMAD signaling. Furthermore, GLSO elevated SMAD2/3 expression in skin burn and promoted its nuclear translocation, and TRPV1 expression was also increased upon exposure to GLSO. Cell proliferation and immunofluorescence assays with TRPV1 inhibitor showed that GLSO accelerated skin burn wound healing through TRPV1 and SMADs signaling, which provides a foundation for clinical application of GLSO in the healing of deep skin burns.

Hypouricemic effect of 2,4-dihydroxybenzoic acid methyl ester in hyperuricemic mice through inhibiting XOD and down-regulating URAT1.

In this paper, we reported the hypouricemic effect of 2,4-dihydroxybenzoic acid methyl ester (DAE), a component of Ganoderma applanatum, in hyperuricemic mice through inhibiting XOD and down-regulating URAT1. Computationally, DAE showed a high similarity to allopurinol and depicted a high affinity in docking to XOD. In vitro, DAE exhibited an inhibitory effect against XOD. Importantly, DAE demonstrated a remarkable hypouricemic effect, decreasing serum uric acids (SUAs) of hyperuricemic mice (407 ± 31 µmol/L) to 195 ± 23, 145 ± 33 and 134 ± 16 µmol/L (P < 0.01) at the doses of 20, 40, and 80 mg/kg with a dose-dependent manner and showing efficacies at 54-68 %, which were close to the efficacies of allopurinol (61 %) and benzbromarone (57 %). DAE depicted higher and negatively dose-independent urinary uric acids in comparison with that of the hyperuricemic control, implying DAE exerted an uricosuric effect and also a reduction effect on uric acid production. Unlike toxic allopurinol and benzbromarone, no general toxicity on body weights and no negative influence on liver, kidney, spleen and thymus were observed for DAE. Mechanistically, DAE inhibited XOD activities in vivo. Moreover, DAE up-regulated OAT1 and down-regulated GLUT9, URAT1 and CNT2. Overall, DAE may present a hypouricemic effect through inhibiting XOD and up-regulating OAT1 and down-regulating GLUT9, URAT1 and CNT2. This work provided novel insights into the hypouricemic effect of DAE and G. applanatum.

Caffeic acid phenethyl ester alleviated hypouricemia in hyperuricemic mice through inhibiting XOD and up-regulating OAT3.

BACKGROUND: Hyperuricemia is characterized with high serum uric acids (SUAs) and directly causes suffering gout. Caffeic acid phenethyl ester (CAPE) is widely included in dietary plants and especially propolis of honey hives. HYPOTHESIS/PURPOSE: Since CAPE exerts a property resembling a redox shuttle, the hypothesis is that it may suppress xanthine oxidase (XOD) and alleviate hyperuricemia. The aim is to unveil the hypouricemic effect of CAPE and the underlying mechanisms. METHODS: By establishing a hyperuricemic model with potassium oxonate (PO) and hypoxanthine (HX) together, we investigated the hypouricecmic effect of CAPE. On this model, the expressions of key mRNAs and proteins, including glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), and the activity of XOD were assayed in vivo. Also, the inhibitory effect of CAPE against XOD was assayed in vitro through enzymatic activity tests and by molecular docking. RESULTS: CAPE demonstrated a remarkable hypouricemic effect, which reduced the SUAs of hyperuricemic mice (401 ± 111 µmol/l) to 209 ± 56, 204 ± 65 and 154 ± 40 µmol/l (p < 0.01) at the doses of 15, 30 and 60 mg/kg respectively, depicting efficacies between 48 and 62% and approaching allopurinol's efficacy (52%). Serum parameters, body weights, inner organ coefficients, and H&E staining suggested that CAPE displayed no general toxicity and it alleviated the liver and kidney injuries caused by hyperuricemia. Mechanistically, CAPE decreased XOD activities significantly in vivo, presented an IC50 at 214.57 µM in vitro and depicted a favorable binding to XOD in molecular simulation, indicating that inhibiting XOD may be an underlying mechanism of CAPE against hyperuricemia. CAPE did decreased GLUT9 protein and down-regulated URAT1 mRNA and protein. In addition, CAPE up-regulated ATP binding cassette subfamily G member 2 (ABCG2) and organic anion transporter 3 (OAT3) mRNA and proteins in comparison with that of the hyperuricemic control. All above, CAPE may alleviate hyperuricmia through inhibiting XOD, decreasing GLUT9 and URAT1 and increasing ABCG2 and OAT3. CONCLUSION: CAPE presented potent hypouricemic effect in hyperuricemic mice through inhibiting XOD activity and up-regulating OAT3. CAPE may be a promising treatment against hyperuricemia.

Immunoregulatory activity of a low-molecular-weight heteropolysaccharide from Ganoderma leucocontextum fruiting bodies in vitro and in vivo.

The chemical structure of GLP-1, a novel water-soluble heteropolysaccharide purified Ganoderma leucocontextum fruiting bodies, has been characterized in our previous study. This study aimed to investigate the immunostimulatory activity of GLP-1 in vitro and in vivo by using RAW264.7 macrophages and cyclophosphamide-induced immunosuppressed mice model. Results showed that GLP-1 was able to enhance phagocytic activity and promote the production of reactive oxygen species, nitric oxide, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 in RAW264.7 macrophages. Moreover, GLP-1 could activate mitogen-activated protein kinase, phosphatidylinositol-3-kinase/protein kinase B, and nuclear factor-kappa B signaling pathways through toll-like receptor 2 and dectin-1 receptors. Furthermore, GLP-1 increased the thymus index, serum immunoglobulin levels, and percentage of CD3+ T lymphocytes in cyclophosphamide-induced immunosuppressed mice. These results demonstrated that GLP-1 possessed significant immunostimulatory effects in vivo and in vitro and could be developed as an effective immunomodulator for application in functional foods.

Preparation, chemical structure, and immunostimulatory activity of a water-soluble heteropolysaccharide from Suillus granulatus fruiting bodies.

A water-soluble heteropolysaccharide (SGP2-1) was purified from Suillus granulatus fruiting bodies by anion-exchange chromatography and gel permeation chromatography. The structural characteristics were analyzed by high-performance gel permeation chromatography, high-performance liquid chromatography, Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy. The immunostimulatory activity was investigated using RAW 264.7 macrophages. Results showed that SGP2-1 with weight average molecular weight of 150.75 kDa was composed of mannose, glucose, and xylose. The backbone of SGP2-1 was mainly composed of â†’ 4)-α-Glcp-(1→, and the terminal group α-d-Glcp â†’ was linked to the main chain by O-6 position. SGP2-1 could significantly enhance pinocytic capacity, reactive oxygen species production, and cytokines secretion. SGP2-1 exerted immunomodulatory effects through interacting with toll-like receptor 2, and activating mitogen-activated protein kinase, phosphatidylinositol-3-kinase/protein kinase B, and nuclear factor-kappa B signaling pathways. These findings indicated that SGP2-1 could be explored as a potential immunomodulatory agent for application in functional foods.