Structural characterization and immunomodulatory activity of a polysaccharide from Dioscotea opposita.

The purified polysaccharides fraction, DOP-2, was prepared from Dioscorea opposita Thunb (D. opposita). This study combined in vitro and in vivo experiments to comprehensively investigate the index changes in RAW264.7 cells and immunocompromised mice under DOP-2 intervention, aiming to elucidate the potential mechanisms of immunomodulatory effects of DOP-2. DOP-2 (10 âˆ¼ 500 µg/mL) significantly elevated the levels of NO, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) factors secreted by RAW264.7 cells, and restored the body weight of immunosuppressed mice and improve the degree of injury to the immune organ index, resulting in significant immunomodulatory effects. Notably, DOP-2 promoted the production of short-chain fatty acids (SCFAs) in immunosuppressed mice and modulated the composition of their gut microflora. These findings highlight the potential benefits of DOP-2 therapy in improving immune function and gut health, and will provide a theoretical basis for the application of D. opposita polysaccharides as an immunomodulatory adjuvant.

A glucuronogalactomannan isolated from Tetrastigma hemsleyanum Diels et Gilg: Structure and immunomodulatory activity.

A novel acidic glucuronogalactomannan (STHP-5) was isolated from the aboveground part of Tetrastigma hemsleyanum Diels et Gilg with a molecular weight of 3.225 × 105 kDa. Analysis of chain conformation showed STHP-5 was approximately a random coil chain. STHP-5 was composed mainly of galactose, mannose, and glucuronic acid. Linkages of glycosides were measured via methylation analysis and verified by NMR. In vitro, STHP-5 induced the production of nitric oxide (NO) and secretion of IL-6, MCP-1, and TNF-α in RAW264.7 cells, indicating STHP-5 had stimulatory activity on macrophages. STHP-5 was proven to function as a TLR4 agonist by inducing the secretion of secreted embryonic alkaline phosphatase (SEAP) in HEK-Blue™-hTLR4 cells. The TLR4 activation capacity was quantitatively measured via EC50, and it showed purified polysaccharides had stronger effects (lower EC50) on activating TLR4 compared with crude polysaccharides. In conclusion, our findings suggest STHP-5 may be a novel immunomodulator.

Structural characterization of a Chlorella heteropolysaccharide by analyzing its depolymerized product and finding an inducer of human dendritic cell maturation.

Chlorella polysaccharides have been gaining increasing attention because of their high yield from dried Chlorella powder and their remarkable immunomodulatory activity. In this study, the major polysaccharide fraction, CPP-3a, in Chlorella pyrenoidosa, was isolated, and its detailed structure was investigated by analyzing the low-molecular-weight product prepared via free radical depolymerization. The results indicated that CPP-3a with a molecular weight of 195.2 kDa was formed by →2)-α-L-Araf-(1→, →2)-α-D-Rhap-(1→, →5)-α-L-Araf-(1→, →3)-ß-D-Glcp-(1→, →4)-α-D-Glcp-(1→, →4)-α-D-GlcpA-(1→, →2,3)-α-D-Manp-(1→, →3,4)-α-D-Manp-(1→, →3,4)-ß-D-Galp-(1→, →3,6)-ß-D-Galp-(1→, and →2,3,6)-α-D-Galp-(1→ residues, branched at C2, C3, C4, or C6 of α/ß-D-Galp and α-D-Manp, and terminated by α/ß-L-Araf, α-L-Arap, α-D-Galp, and ß-D-Glcp. Biological assays showed that CPP-3a significantly altered the dendritic morphology of immature dendritic cells (DCs). Enhanced CD80, CD86, and MHC I expression on the cell surface and decreased phagocytic ability indicated that CPP-3a could induce the maturation of DCs. Furthermore, CPP-3a-stimulated DCs not only stimulated the proliferation of allogeneic naïve CD4+ T cells and the secretion of IFN-γ, but also directly stimulated the activation and proliferation of CD8+ T cells through cross-antigen presentation. These findings indicate that CPP-3a can promote human DC maturation and T-cell stimulation and may be a novel DC maturation inducer with potential developmental value in DC immunotherapy.

Structural elucidation and immunomodulatory activities in vitro of type I and II arabinogalactans from different origins of Astragalus membranaceus.

Astragalus membranaceus polysaccharide (APS) possesses excellent immunomodulatory activity. However, there are several studies on the structural characterization of APS. Here, we aimed to elucidate the repeating units of polysaccharides (APS1, 106.5 kDa; APS2, 114.5 kDa) obtained from different Astragalus membranaceus origins and further investigated their immunomodulatory activities. Based on structural analysis, types of the two polysaccharides were identified as arabinogalactan-I (AG-I) and arabinogalactan-II (AG-II), and co-elution of arabinogalactans (AGs) and α-glucan was observed. The backbone of AG-I was 1,4-linked ß-Galp occasionally substituted by α-Araf at O-2 and/or O-3. AG-II was a highly branched polysaccharide with long branches of α-Araf, which were attached to the O-3 of 1,6-linked ß-Galp of the backbone. The presence of AGs in A. membranaceus was confirmed for the first time. The two polysaccharides could promote the expression of IL-6, IL-1ß and TNF-α in RAW264.7 cells via MAPKs and NF-κB signaling pathways. The constants for APS1 and APS2 binding to Toll-like receptor 4 (TLR4) were 1.83 × 10-5 and 2.08 × 10-6, respectively. Notably, APS2 showed better immunomodulatory activity than APS1, possibly because APS2 contained more AGs. Hence, the results suggested that AGs were the vital components of APS in the immunomodulatory effect.

Egg Yolk Selenopeptides: Preparation, Characterization, and Immunomodulatory Activity.

In this study, egg yolk selenium peptides (Se-EYP) were prepared using double-enzyme hydrolysis combined with a shearing pretreatment. The properties of the selenopeptides formed were then characterized, including their yield, composition, molecular weight distribution, antioxidant activity, in vitro digestion, and immunomodulatory activity. The peptide yield obtained after enzymatic hydrolysis using a combination of alkaline protease and neutral protease was 74.5%, of which 82.6% had a molecular weight <1000 Da. The selenium content of the lyophilized solid product was 4.01 µg/g. Chromatography-mass spectrometry analysis showed that 88.6% of selenium in Se-EYP was in the organic form, of which SeMet accounted for 60.3%, SeCys2 for 21.8%, and MeSeCys for 17.9%. After being exposed to in vitro simulated digestion, Se-EYP still had 65.1% of oligopeptides present, and the in vitro antioxidant activity was enhanced. Moreover, Se-EYP exhibited superior immune detection indices, including immune organ index, level of immune factors in the serum, histopathological changes in the spleen, and selenium content in the liver. Our results suggest that Se-EYP may be used as selenium-enriched ingredients in functional food products.

Unlocking the Immunomodulatory Potential of Rosmarinic Acid Isolated from Punica granatum L. Using Bioactivity-Guided Approach: In Silico, In Vitro, and In Vivo Approaches.

BACKGROUND: Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. AIM: This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. METHODS: Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. RESULTS: Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. CONCLUSION: Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.

Fucoidan from the cell wall of Silvetia siliquosa with immunomodulatory effect on RAW 264.7 cells.

Silvetia siliquosa, the only species of the family Fucaceae in China, is used as a medicine food homology. Fucoidan from S. siliquosa was extracted by hot water twice thoroughly (13 % of total yield), and a purified fucoidan SSF with a molecular weight of 93 kD was obtained. Chemical composition analysis demonstrated that SSF was primarily composed of sulfate (21.68 wt%) and fucose (84 % of all neutral monosaccharides). IR, methylation analysis, NMR and ESI-MS results indicated SSF had the backbone of mainly (1 â†’ 3)-α-L-fucopyranose and minor (1 â†’ 4)-α-L-fucopyranose, with little 1,3 and 1,4 branched ß-D-Xylp and ß-D-Galp. The in vitro immunomodulatory test on RAW 264.7 cells showed that SSF could up-regulate the expression of immune related factors and proteins in a concentration-dependent manner, but the immunomodulatory effect disappeared from desulfated SSF. This research indicated that highly sulfated fucan possessed immunomodulatory effect and the importance of sulfate groups in the activity of SSF.

Purification, structural characterization, and immunomodulatory activity of two polysaccharides from Portulaca oleracea L.

In present study, two water-soluble polysaccharides designated as POL-1 and POL-2 were purified from purslane and their structural characteristics as well as immunomodulatory activity were investigated. The weight-average molecular weight (Mw) of POL-1 and POL-2 were determined to be 64,100 Da and 21,000 Da, respectively. Comprehensive techniques including UV, IR, GC-MS, and NMR were applied to deduced that POL-1 was a pectin polysaccharide homogalacturonan (HG) consisting of →4)-α-GalpA-(1→ with methyl ester degree of 9.71 % and acetylation degree of 0.34 %, while POL-2 was composed of a 1, 4-linked ß-Galp backbone substituted by short side chain →4)-α-Glcp-(1→ and →6)-α-Glcp-(1→. The →4)-α-Glcp-(1→ was attached at the O-6 position of →4)-ß-Galp-(1→. TEM further revealed that POL-1 was non-branched single chains, while POL-2 was entangled microstructure with side chains. Moreover, POL-2 significantly promoted macrophage phagocytosis as well as the secretion of NO and cytokines (TNF-α, IL-6) through activating NF-κB signaling pathway, thus demonstrating potential immunomodulatory activity. These findings suggested that purslane may be exploited as a potential adjuvant and dietary supplement with immunostimulatory purpose.

Characterization of an exopolysaccharide synthesized by Lacticaseibacillus rhamnosus B6 and its immunomodulatory activity in vitro.

An exopolysaccharide, designated F1, was purified from the fermented milk by Lacticaseibacillus rhamnosus strain B6 (CGMCC No. 13310). F1, with the weight average molecular weight of 1.577 × 106 Da, is consisted of rhamnose, glucose and galactose in a molar ratio of 3.7:1.5: 1. The backbone included 1,3-linked Rha, 1,2,3-linked Rha, 1,2-linked Glc and 1,3-linked Glc residues, with the branching point located at O2 position of 1,2,3-linked Rha residue, and the branch chain composed of terminal linked galactose residue with a pyruvate substituent. F1 could significantly stimulate the phagocytic activity and TNF-α expression in RAW 264.7 macrophages in a dose-dependent manner, and the release of NO at 200 µg/mL as well. F1 at 200 µg/mL could stimulate the expression of the pro-inflammatory cytokine encoding genes including TNF-α and iNOS, but with a negligible upregulating effect on the mRNA expression of IL-10. F1 could up-regulate the expression of NF-κBp65 and skew macrophage polarization towards M1 phenotype. These results suggest F1 elicit an immunomodulatory effect through the NF-κB signaling pathway.

Effect of subcritical water temperature on the chain conformation and immune activity of ginger polysaccharides.

In this study, the ginger polysaccharides extracted from hot water (HW-G) were modified with subcritical water (SW-G) to effectively regulate their immune activity, and the relationship between polysaccharide chain conformation and immune activity at different subcritical water temperatures was investigated. The results indicated that, compared with HW-G, the xylose and mannose were degraded at high temperatures. The molecular weight of ginger polysaccharide decreased from 1.083 × 106 g/mol to 3.113 × 105 g/mol after subcritical water modification (100-160 °C). The chain conformation transitioned from rigid rod chain to semi-rigid chain and eventually to random coil. The degree of relaxation of the polysaccharide chains showed a continuous increase trend. Additionally, ginger polysaccharide modified by subcritical water at 130 °C was found to promote the proliferation and phagocytosis of 264.7 cells more obviously and signally increase the secretion levels of NO, IL-6, TNF-α and IL-1ß. When the subcritical water temperature exceeds 130 °C, the activity of ginger polysaccharide begins to decline rapidly. These findings demonstrate a close correlation between polysaccharide chain conformation and immunomodulatory activity, confirming the feasibility of the subcritical water temperature effect as a means of immune activity regulation, which opens up a new approach to obtaining highly active polysaccharides.

An arabinose-rich heteropolysaccharide isolated from Belamcanda chinensis (L.) DC treats liver cancer by targeting FAK and activating CD40.

An undisclosed polysaccharide, BCP80-2, was isolated from Belamcanda chinensis (L.) DC. Structural investigation revealed that BCP80-2 consists of ten monosaccharide residues including t-α-Araf-(1→, →3,5)-α-Araf-(1→, →5)-α-Araf-(1→, →4)-ß-Xylp-(1→, →3)-α-Rhap-(1→, →4)-ß-Manp-(1→, t-ß-Glcp-(1→, →6)-α-Glcp-(1→, t-ß-Galp-(1→, and→3)-α-Galp-(1→. In vivo activity assays showed that BCP80-2 significantly suppressed neoplasmic growth, metastasis, and angiogenesis in zebrafish. Mechanistic studies have shown that BCP80-2 inhibited cell migration of HepG2 cells by suppressing the FAK signaling pathway. Moreover, BCP80-2 also activated immunomodulation and upregulated the secretion of co-stimulatory molecules CD40, CD86, CD80, and MHC-II. In conclusion, BCP80-2 inhibited tumor progression by targeting the FAK signaling pathway and activating CD40-induced adaptive immunity.

Melanoidin-like carbohydrate-containing macromolecules from Shanxi aged vinegar exert immunoenhancing effects on macrophage RAW264.7 cells.

Bioactive macromolecule mining is important for the functional chemome analysis of traditional Chinese vinegar. In this study, we isolated and characterized carbohydrate-containing macromolecules from Shanxi aged vinegar (CCMSAV) and evaluated their immunomodulatory activity. The isolation process involved ethanol precipitation, deproteinization, decolorization, and DEAE-650 M column chromatography, resulting in the acquisition of four sub-fractions. All sub-fractions exhibited a molecular weight range of 6.92 to 16.71 kDa and were composed of 10 types of monosaccharides. Comparative analysis of these sub-fractions with two melanoidins exhibited similarities in elemental composition, spectral signature, and pyrolytic characteristics. Immunological assays confirmed the significantly enhanced cell viability, phagocytic activity, and secretion of nitric oxide, tumor necrosis factor (TNF)-α and interleukin (IL)-6 in RAW264.7 cells by all four sub-fractions. Further investigation of the immunomodulatory mechanism revealed that SAV-RP70-X, the most potent purified sub-fraction, enhanced aerobic glycolysis in macrophages and activated Toll-like receptor 2 (TLR2), TLR4, mannose receptor (MR), scavenger receptor (SR), and the dendritic cell-associated C-type lectin-1 receptor (Dectin-1). Furthermore, the activation of macrophages was associated with the MyD88/PI3K/Akt/NF-κB signaling pathway. Methylation analysis revealed that 1,4-Xylp was the most abundant glycosidic linkage in SAV-RP70-X.

Programmable Electro-Assembly of Collagen: Constructing Porous Janus Films with Customized Dual Signals for Immunomodulation and Tissue Regeneration in Periodontitis Treatment.

Currently available guided bone regeneration (GBR) films lack active immunomodulation and sufficient osteogenic ability- in the treatment of periodontitis, leading to unsatisfactory treatment outcomes. Challenges remain in developing simple, rapid, and programmable manufacturing methods for constructing bioactive GBR films with tailored biofunctional compositions and microstructures. Herein, the controlled electroassembly of collagen under the salt effect is reported, which enables the construction of porous films with precisely tunable porous structures (i.e., porosity and pore size). In particular, bioactive salt species such as the anti-inflammatory drug diclofenac sodium (DS) can induce and customize porous structures while enabling the loading of bioactive salts and their gradual release. Sequential electro-assembly under pre-programmed salt conditions enables the manufacture of a Janus composite film with a dense and DS-containing porous layer capable of multiple functions in periodontitis treatment, which provides mechanical support, guides fibrous tissue growth, and acts as a barrier preventing its penetration into bone defects. The DS-containing porous layer delivers dual bio-signals through its morphology and the released DS, inhibiting inflammation and promoting osteogenesis. Overall, this study demonstrates the potential of electrofabrication as a customized manufacturing platform for the programmable assembly of collagen for tailored functions to adapt to specific needs in regenerative medicine.

The isolation, characterization and biological activities of the non-glucan polysaccharides from the high-starch-content plant Pueraria mirifica.

The dried root of Pueraria mirifica (P. mirifica) is an edible foodstuff widely used in Asian countries. P. mirifica is known for its high starch content. The isolation of polysaccharides from high-starch plant parts is challenging due to the interference of starch. Therefore, this study aimed to develop a technique for isolating and investigating the structure and activity of non-glucan polysaccharides from P. mirifica (PMP). An effective starch removal process was developed using α-amylase hydrolysis and thorough membrane dialysis. Four non-glucan polysaccharides were isolated, and PMP-2 was subjected to structural elucidation. The results indicated that PMP-2 has a molecular weight of 124.4 kDa and that arabinose and galactose are the main components, accounting for 27.8 % and 58.5 %, respectively. Methylation and NMR analysis suggested that PMP-2 is an Arabinogalactan composed of 1,6-linked Galp and 1,4-linked Galp as the main chain, with arabinan and rhamnose as side chains. Furthermore, PMP-C and PMP-2 exhibited concentration-dependent antioxidant activities against DPPH, ABTS, and hydroxyl radicals and certain immunomodulatory activities related to the release of NO, TNF-α and IL-6. These findings suggest that PMP-2 has potential therapeutically active ingredient in functional foods. The developed method successfully removed starch and isolated non-glucan polysaccharides from the high-starch content plant P. mirifica and can be applied to other high-starch plants.

The differential non-covalent binding of epicatechin and chlorogenic acid to ovotransferrin and the enhancing efficiency of immunomodulatory activity.

Seeking safe and environmentally friendly natural immunomodulators is a pressing requirement of humanity. This study investigated the differential binding characteristics of two polar polyphenols (PP), namely epicatechin (EC) and chlorogenic acid (CA), to ovotransferrin (OVT), and explored the relationship between structural transformations and immunomodulatory activity of OVT-PP complexes. Results showed that CA exhibited a stronger affinity for OVT than EC, mainly driven by hydrogen bonds and van der Waals forces. Complexation-induced conformational variations in OVT, including static fluorescence quenching, increased microenvironment polarity surrounding tryptophan and tyrosine residues, and the transition from disordered α-helix to stable ß-sheet. Furthermore, the structural conformation transformation of OVT-PP complexes facilitated the enhancement of immunomodulatory activity, with the OVT-CA (10:2) complex demonstrating the best immunomodulatory activity. Principal component analysis (PCA) and Pearson correlation analysis revealed the immunomodulatory activities of the OVT-PP complexes were influenced by surface hydrophobicity (negatively correlated), ß-sheet percentage and polyphenol binding constants. It could be inferred that PP complexation increased the surface polarity of OVT, consequently enhancing its immunomodulatory activity by promoting cell membrane affinity and antigen recognition. This study provides valuable guidance for effectively utilizing polyphenol-protein complexes in enhancing immunomodulatory activity.

Structural characterization, chain conformation and immunomodulatory activity of a heteropolysaccharide from Inonotus hispidus.

A new polysaccharide (IHP-1aa) was isolated from the fruiting body of Inonotus hispidus by hot water extraction, ethanol precipitation and column chromatography. The molecular weight of IHP-1aa was 26.9 kDa. Structural analysis showed that IHP-1aa consisted of glucose (Glc), galactose (Gal), fucose (Fuc), mannose (Man) and contained a certain amount of 3-O-methylgalactose (3-O-Me-Gal). The structure was mainly composed of →6)-α/ß-D-Glcp-(1→, →6)-α-D-Galp-(1→, →6)-(3-O-Me)-α-D-Galp-(1→, →6)-α-D-Manp-(1 â†’ and →2, 6)-α-D-Galp-(1 â†’ as the main chain. Branched at O-2 with single ß-L-Fucp-(1 â†’ 6)-α-D-Galp-(1 â†’ 6)-α-D-Glcp-(1 â†’ as major the side chain. The results of SEM, XRD and AFM combined with Congo red indicated that IHP-1aa may be amorphous granular chain conformation. In addition, IHP-1aa stimulated macrophage function and improved phagocytic ability of RAW264.7, as well as promoted the secretion of NO, TNF-α and IL-6. IHP-1aa, a 3-O-methylgalactose-containing heteropolysaccharide, was isolated for the first time from the I. hispidus, which may be used as a potential immunomodulator in functional foods.

Sciadonic acid ameliorates cyclophosphamide-induced immunosuppression by modulating the immune response and altering the gut microbiota.

BACKGROUND: Cyclophosphamide (Cy) is a frequently used chemotherapeutic drug, but long-term Cy treatment can cause immunosuppression and intestinal mucosal damage. The intestinal mucosal barrier and gut flora play important roles in regulating host metabolism, maintaining physiological functions and protecting immune homeostasis. Dysbiosis of the intestinal flora affects the development of the intestinal microenvironment, as well as the development of various external systemic diseases and metabolic syndrome. RESULTS: The present study investigated the influence of sciadonic acid (SA) on Cy-induced immunosuppression in mice. The results showed that SA gavage significantly alleviated Cy-induced immune damage by improving the immune system organ index, immune response and oxidative stress. Moreover, SA restored intestinal morphology, improved villus integrity and activated the nuclear factor κB signaling pathway, stimulated cytokine production, and reduced serum lipopolysaccharide (LPS) levels. Furthermore, gut microbiota analysis indicated that SA increased t beneficial bacteria (Alistipes, Lachnospiraceae_NK4A136_group, Rikenella and Odoribacter) and decreased pathogenic bacteria (norank-f-Oscillospiraceae, Ruminococcus and Desulfovibrio) to maintain intestinal homeostasis. CONCLUSION: The present study provided new insights into the SA regulation of intestinal flora to enhance immune responses. © 2024 Society of Chemical Industry.

Fecal fermentation behavior and immunomodulatory activity of arabinoxylan from wheat bran.

Arabinoxylan (AX) is the predominant non-starch polysaccharide in wheat bran, known for its significant immunomodulatory activity. However, existing literature lacks comprehensive studies on AX fermentation by gut microbiota and its subsequent immunomodulatory mechanisms. In the present study, we aimed to investigate the effects of AX on the composition of gut microbiota and the characteristics of its immunomodulatory activity. For this purpose, an in vitro fermentation system and a cyclophosphamide-induced immunosuppressed mouse model were established to explore both the in vitro and in vivo effects of AX on gut microbiota and immune modulation. The results demonstrated that AX was metabolized by gut microbes and in turn to promoting the production of short-chain fatty acids (SCFAs), which concurrently led to a significant decrease in pH. Furthermore, AX treatment significantly changed the microbial composition, elevated the relative abundance of Actinobacteria while reducing that of Bacteroidetes. In the immunosuppressed mice, AX administration improved the thymus and spleen indices, mitigated spleen injury, and bolstered overall immunity. Moreover, AX altered the gut microbiota structure, increasing the abundance of Bacteroidetes and decreasing that of Firmicutes. These findings suggest that wheat bran-derived AX can modulate intestinal microbial composition, improve gut microecology, and enhance host immunity by targeting gut microbiota.

Immunomodulatory and antibacterial effect of red wine concentrate rich in a natural complex of polyphenols under diabetes mellitus.

Changes in immunocompetent cells influence the course of diabetes mellitus and contribute to its complications. Thus, correction of diabetes-induced immune system disorders is vital for normalizing the state of the organism. Red wine polyphenols due to their biological activities could be considered a potential remedy for correcting diabetes. The study aimed to evaluate the antimicrobial potential and the influence of red wine polyphenols on immune system in streptozotocin-induced diabetes. We studied immunological parameters, i.e. quantity of white blood cells in peripheral blood and peritoneal macrophages, the bactericidal activity of phagocytes of blood, the activity of myeloperoxidase, and the level of cationic proteins in these cells after the administration of the polyphenol-rich red wine concentrate (PC concentrate) of known composition, obtained from Ukrainian wine, for 14th day to rats with streptozotocin-induced diabetes. The Minimal Bactericidal Concentration (MBC) of the PC concentrate was determined with the Broth Microdilution method. The PC concentrate normalized the quantity and functional activity of peripheral blood neutrophils and peritoneal macrophages, and decreased the quantity of lymphocytes under diabetes, as well as possessed the antibacterial activity against Staphylococcus aureus and Escherichia coli. Our results indicate the significant biological potential of the PC concentrate and its therapeutic relevance to correct diabetes-induced disorders.

Immunomodulatory effects of copper nanoparticles against mitogen-stimulated rat splenic and thymic lymphocytes.

In the present study, we have evaluated the effects of copper (Cu) nanoparticles (NPs) on the primary B-and T-lymphocytes proliferation, cytokine levels, and bio-distribution through in vitro, in vivo and ex-vivo studies to allow the possible exploitations of CuNPs in biomedical applications. CuNPs were characterized by UV-Visible spectroscopy, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). The proliferative response of lymphocytes was studied by 3H-thymidine incorporation assay and lymphocyte viability through trypan blue assay. The bio-distribution of CuNPs into lymphoid organs was examined by using ex-vivo imaging system. Cytokine levels in plasma of control and CuNPs treated animal groups were determined by enzyme-linked immunosorbent assay (ELISA) method along with other biochemical analysis. CuNPs significantly suppressed the proliferation of primary splenic and thymic lymphocytes in a dose dependent manner. Ex-vivo imaging exhibited the distribution of CuNPs in spleen and thymus. Oral administration of CuNPs (2 mg and 10 mg/kg body weight) significantly inhibited the proliferation of splenic and thymic lymphocytes along with lowered cytokines levels (TNF-alpha and IL-2) on comparison with controls. The results indicated the significant inhibition of lymphocytes proliferative response and secretion of cytokines, thus unveiling the immunomodulatory effects of CuNPs.