Swarna Bhasma Induces Antigen-Presenting Abilities of Macrophages and Helps Antigen Experienced CD4+ T Cells to Acquire Th1 Phenotypes Against Leishmania donovani Antigens.

In leishmaniasis, the protective immunity is largely mediated by proinflammatory cytokine producing abilities of T cells and an efficient parasite killing by phagocytic cells. Notwithstanding a substantial progress that has been made during last decades, the mechanisms or factors involved in establishing protective immunity against Leishmania are not identified. In ancient Indian literature, metallic "bhasma," particularly that of "swarna" or gold (fine gold particles), is indicated as one of the most prominent metal-based therapeutic medicine, which is known to impart protective and curative properties in various health issues. In this work, we elucidated the potential of swarna bhasma (SB) on the effector properties of phagocytes and antigen-activated CD4+ T cells in augmenting the immunogenicity of L. donovani antigens. The characterization of SB revealing its shape, size, composition, and measurement of cytotoxicity established the physiochemical potential for its utilization as an immunomodulator. The activation of macrophages with SB enhanced their capacity to produce nitric oxide and proinflammatory cytokines, which eventually resulted in reduced uptake of parasites and their proliferation in infected cells. Further, in Leishmania-infected animals, SB administration reduced the generation of IL-10, an anti-inflammatory cytokine, and enhanced pro-inflammatory cytokine generation by antigen activated CD4+ T cells with increased frequency of double (IFNγ+/TNFα+) and triple (IFNγ+TNFα+IL-2+) positive cells and abrogated disease pathogeneses at the early days of infection. Our results also suggested that cow-ghee (A2) emulsified preparation of SB, either alone or with yashtimadhu, a known natural immune modulator which enhances the SB's potential in enhancing the immunogenicity of parasitic antigens. These findings suggested a definite potential of SB in enhancing the effector functions of phagocytes and CD4+ T cells against L. donovani antigens. Therefore, more studies are needed to elucidate the mechanistic details of SB and its potential in enhancing vaccine-induced immunity.

Terpenoid-lupeol of red dragon fruit (Hylocereus polyrhizus) and its immunomodulatory activity.

Red dragon fruit (Hylocereus polyrhizus, (F.A.C. Weber) Britton and Rose) has been reported to have various biological activities such as antimicrobial, anti-hypercholesterolemia, anti-diabetes mellitus, cardiovascular risk reduction, health supplement, and melanoma cell inhibitory. The red thick peel of this fruit is just practically a waste that is possibly utilized to maintain health, therefore this research aimed to isolate and identify active compounds of H. Polyrhizus peels which can improve the immune system of body. In order to simplify methanol extract was partition and fractionation. The active compounds of petroleum ether fraction were separated and purified using preparative thin layer chromatography. The identification of the compounds structure was conducted through spectroscopic techniques, including UV, FT-IR, 13CNMR and 1HNMR spectroscopy. The data of spectra revealed that the isolate is lupeol. The statistical analysis of macrophage activity showed that the isolate with concentrations of 100, 50, 25, 12.5 and 6.25µg/mL could activate the macrophages higher than control negative. Terpenoid generated from the isolation of Hylocereus polyrhizus was identified as lupeol (1-isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-eicosahydrocyclopenya [α] chrysen-9ol. In vitro test shows that the isolated compound had an immunomodulatory activity by increases macrophage phagocytosis of latex beads.

Dietary supplementation with Lactobacillus plantarum and ß-glucan affects immune parameters in the tench (Tinca tinca) fry.

The aim of the experiment was to examine the effect of a diet enriched with Lactobacillus plantarum and/or ß-glucan on the immune parameters in the juvenile tench (Tinca tinca). Fish were fed for 14 days different diets (phase 1 of the experiment), a dry commercial starter feed in the control group or the same feed supplemented with: 1% ß-1,3/1,6-glucan in group G, 108 cfu L. plantarum g-1 in group L, 1% ß-1,3/1,6-glucan + 108 cfu L. plantarum g-1 in group G+L. During consecutive 14 days all fish were fed the commercial feed alone (phase 2). The stimulating effects of the tested preparations was evaluated twice, at the end of each experimental phase. Dietary supplementation of ß-1,3/1,6-glucan considerably improved the humoral innate immune response (activity of lysozyme and total Ig) and the pinocytotic activity of phagocytes. Supplement of L. plantarum improved the ability of the head kidney phagocytes (RBA) to carry out oxygen burst in L and G+L groups. A similar effect was observed for the killing activity of phagocytes (PKA) from the head kidney after the stimulation of A. hydrophila, and the effect persisted for two weeks after the commercial feed regime was resumed. A significant increase in the proliferative activity of B lymphocytes originating from the head kidney was observed in groups L and G+L. The study has revealed that the addition of the tested G+L synbiotic to dry diet stimulates the innate immune response mechanisms in the juvenile tench.

Melatonin Action on the Activity of Phagocytes from the Colostrum of Obese Women.

BACKGROUND AND OBJECTIVES: Breastfeeding promotion is an important public health strategy for counter-balancing the negative effects of maternal overweight and obesity. Colostrum contains melatonin, which can attenuate the impacts of excessive maternal weight and boost the infant's immune system. Therefore, the objective of this study was to analyze the effects of melatonin on mononuclear (MN) phagocytes from the colostrum of women with pre-gestational obesity. Materials and Methods: Colostrum samples were collected postpartum from 100 women at a public hospital in São Paulo, Brazil. The donors were divided into two groups: the control group and the high body mass index (BMI) group. Melatonin levels in the colostrum were determined by an ELISA Kit, and the functional activity of MN cells was assessed using the phagocytosis assay by flow cytometry, and reactive oxygen species (ROS), intracellular calcium, and apoptosis were assessed by fluorimetry using a microplate reader. RESULTS: The colostrum of mothers with pre-gestational high BMI exhibited higher melatonin levels (p < 0.05) and lower phagocytosis (p < 0.05) and ROS release (p < 0.05). Superoxide release was similar between the normal and high BMI groups (p > 0.05). Intracellular calcium release and apoptosis were also higher in the high BMI group (p < 0.05). Melatonin levels likely increased the phagocytosis rate and reduced intracellular calcium release and the apoptosis index (p < 0.05). CONCLUSIONS: The results suggest that melatonin is a possible mechanism for maternal-infant protection against obesity and restores the functional activity of colostrum phagocytes in obese mothers.

Osteopontin Attenuates Secondary Neurodegeneration in the Thalamus after Experimental Stroke.

Cortical cerebral ischemia elicits neuroinflammation as well as secondary neuronal degeneration in remote areas. Locally distinct and specific secondary neurodegeneration affecting thalamic nuclei connected to cortical areas highlights such processes. Osteopontin (OPN) is a cytokine-like glycoprotein that is excreted in high amounts after cerebral ischemia and exerts various immunomodulatory functions. We here examined putative protective effects of OPN in secondary thalamic degeneration. We subjected male Wistar rats to photothrombosis and subsequently injected OPN or placebo intracerebroventricularly. Immunohistochemical and fluorescence staining was used to detect the extent of neuronal degeneration and microglia activation. Ex vivo autoradiography with radiotracers available for human in vivo PET studies, i.e., CIS-4-[18F]Fluor-D-Proline (D-cis-[18F]FPRO), and [6-3H]thymidine ([3H]thymidine), confirmed degeneration and proliferation, respectively. We found secondary neurodegeneration in the thalamus characterized by microglial activation and neuronal loss. Neuronal loss was restricted to areas of microglial infiltration. Treatment with OPN significantly decreased neurodegeneration, inflammation and microglial proliferation. Microglia displayed morphological signs of activation without expressing markers of M1 or M2 polarization. D-CIS-[18F]FPRO-uptake mirrored attenuated degeneration in OPN-treated animals. Notably, [3H]thymidine and BrdU-staining revealed increased stem cell proliferation after treatment with OPN. The data suggest that OPN is able to ameliorate secondary neurodegeneration in thalamic nuclei. These effects can be visualized by radiotracers D-CIS-[18F]FPRO and [3H]thymidine, opening new vistas for translational studies. Graphical Abstract Intracerebroventricular injection of osteopontin attenuates thalamic degeneration after cortical ischemia (pink area). Disruption of thalamocortical connections (blue) and degeneration of thalamic nuclei (encircled) leads to microglia activation. Osteopontin protects from both neurodegeneration and microglia activation as assessed by histological analysis and autoradiograpic studies.

Nanoparticle Ligand-Decoration Procedures Affect in Vivo Interactions with Immune Cells.

Ligand-decorated nanoparticles are extensively studied and applied for in vivo drug delivery and molecular imaging. Generally, two different ligand-decoration procedures are utilized; ligands are either conjugated with nanoparticle ingredients and incorporated during nanoparticle preparation, or they are attached to preformed nanoparticles by utilizing functionalized reactive surface groups (e.g., maleimide). Although the two procedures result in nanoparticles with very similar physicochemical properties, formulations obtained through the latter manufacturing process typically contain nonconjugated reactive surface groups. In the current study, we hypothesized that the different ligand-decoration procedures might affect the extent of interaction between nanoparticles and immune cells (especially phagocytes). In order to investigate our hypothesis, we decorated lipidic nanoparticles with a widely used cyclic Arg-Gly-Asp (cRGD) peptide using the two different procedures. As proven from in vivo experiments in mice, the presence of nonconjugated surface moieties results in increased recognition by the immune system. This is important knowledge considering the emerging focus on understanding and optimizing ways to target and track immune cells and the development of nanomedicine-based strategies in the field of immunotherapy.

The effect of ß-1,3-glucan derived from Euglena gracilis (Algamune™ ) on the innate immunological responses of Nile tilapia (Oreochromis niloticus L.).

Algamune™ is a commercial additive produced from Euglena gracilis, providing a rich source of the ß-1,3-glucan paramylon. Isolated kidney phagocytes of Nile tilapia were incubated with graded doses (0, 8, 16, 32, 64 and 128 µg/ml) of Algamune™ and purified paramylon to gauge their ability to elicit the production of reactive oxygen species. A linear response was observed for extracellular superoxide anion for both sources but only Algamune™ for intracellular superoxide anion. After corroborating the immunostimulant properties ex vivo, a feeding trial was conducted to evaluate the dietary supplementation of Algamune™ (0, 100, 200, 400 and 800 mg/kg of diet) for Nile tilapia. Fish were fed for 3 weeks, after which, fish were sampled for blood and head kidney phagocytes. The remaining fish were challenged with Streptococcus iniae. Macrophage extracellular superoxide anion production was significantly elevated in fish fed diets with 200 mg of Algamune™ kg-1 when compared to fish fed the basal diet. Even though the disease challenge did not show statistical differences, it is worth mentioning that fish fed intermediate doses of Algamune™ had lowest numerical mortality values. Therefore, Algamune™ was demonstrated to enhance some immunological responses of tilapia both in ex vivo and in vivo.

Flavonoids of Artocarpus heterophyllus Lam. heartwood inhibit the innate immune responses of human phagocytes.

OBJECTIVES: To investigate the effects of flavonoids isolated from Artocarpus heterophyllus. heartwood on chemotaxis, phagocytosis, reactive oxygen species (ROS) production and myeloperoxidase (MPO) activity of human phagocytes. METHODS: Chemotaxis was evaluated using a modified Boyden chamber and phagocytosis was determined by flowcytometer. Respiratory burst was investigated by luminol-based chemiluminescence assay while MPO activity was determined by colorimetric assay. KEY FINDINGS: Artocarpanone and artocarpin strongly inhibited all steps of phagocytosis. Artocarpanone and artocarpin showed strong chemotactic activity with IC50 values of 6.96 and 6.10 µm, respectively, which were lower than that of ibuprofen (7.37 µm). Artocarpanone was the most potent compound in inhibiting ROS production of polymorphonuclear leucocytes and monocytes with IC50 values comparable to those of aspirin. Artocarpin at 100 µg/ml inhibited phagocytosis of opsonized bacteria (28.3%). It also strongly inhibited MPO release with an IC50 value (23.3 µm) lower than that of indomethacin (69 µm). Structure-activity analysis indicated that the number of hydroxyl group, the presence of prenyl group and variation of C-2 and C-3 bonds might contribute towards their phagocytosis. CONCLUSIONS: Artocarpanone and artocarpin were able to suppress strongly the phagocytosis of human phagocytes at different steps and have potential to be developed into potent anti-inflammatory agents.

ß-1,3 glucan derived from Euglena gracilis and Algamune™ enhances innate immune responses of red drum (Sciaenops ocellatus L.).

To reduce susceptibility to stressors and diseases, immune-modulators such as ß-glucans have been proven effective tools to enhance the innate immune responses of fish. Consequently, commercial sources of this polysaccharide are becoming increasingly more available. Algamune™ is a commercial additive produced from Euglena gracilis, as a source of linear ß-1,3-glucan. In order to evaluate the immunomodulatory effects of this ß-glucan product, the present study assessed the innate immune parameters of red drum (Sciaenops ocellatus) exposed to Algamune™ ex vivo and in vivo. Isolated kidney phagocytes were incubated with graded concentrations (0, 0.2, 0.4, 0.8, 1.6 and 3.2 mg L-1) of dried Euglena gracilis (Algamune™) as well as purified Paramylon (linear ß-1,3 glucan). Increased bactericidal activity against Streptococcus iniae, and production of intracellular O2- anion superoxide were stimulated by both ß-glucan sources. A reduced activity of extracellular anion superoxide was observed by the phagocytes incubated with Algamune ™. After corroborating the effectiveness of the glucan source ex vivo, a feeding trial was conducted using red drum juveniles (∼26.6 g initial weight). Fish were fed diets with graded levels of Algamune™ (0, 100, 200, 400 and 800 mg kg-1) twice daily for 21 days. No significant differences were detected regarding production performance parameters. At the end of the feeding trial, blood, intestinal content, and kidney were sampled. Intestinal microbiota from fecal material was analyzed through denaturing gradient gel electrophoresis (DGGE) and found to be similar among all treatments. No significant differences were detected for oxidative radical production from whole blood, and isolated phagocytes, and plasma lysozyme activity. However, the total hemolytic activity of red drum plasma was increased in fish fed 100 and 200 mg kg-1 of dietary Algamune™ when compared to fish fed the basal diet. Based on results from both ex vivo and in vivo trials, ß-glucan from Algamune™ was demonstrated to have a moderate immunostimulatory effects on red drum.

Immunization with Larrea divaricata Cav. proteins elicits opsonic antibodies against Pseudomonas aeruginosa and induces phagocytic activity of murine macrophages.

Pseudomonas aeruginosa is an opportunistic pathogen implicated in nosocomial infections for which no vaccines have been approved. Larrea divaricata Cav. (Jarilla) is a widely spread plant in America and it is used in folk medicine to treat several pathologies. It has also been shown that antibodies elicited against Jarilla proteins of crude extract (JPCE) cross-react with proteins from gram-negative bacteria. In this study we aim to assess the contribution of anti-JPCE antibodies in the opsonophagocytosis of P. aeruginosa by murine macrophages. Levels of reactivity of anti-JPCE IgG and IgA antibodies against cell and membrane proteins suggest that these proteins induce a response that could favor opsonic bacterial recognition, which is important for the elimination of bacteria on mucous membranes, useful in the early stages of infection. Opsonophagocytosis assays also show that these antibodies could favor bacteria intake. These results together with previous observations that indicate that anti-JPCE antibodies are able to neutralize P. aeruginosa enzymes point L. divaricata proteins as candidates for vaccine development.

Caffeic acid combined with autoclaved Leishmania major boosted the protection of infected BALB/c mice by enhancing IgG2 production, IFN-γ/TGF-ß and iNO synthase/arginase1 ratios, and the death of infected phagocytes.

BACKGROUND: Immunization with killed Leishmania promastigotes without adjuvant was considered as safe, but gave variable rates of protection. Taking advantage of the immuno-modulatory effect of caffeic acid (CA), a natural polyphenolic antioxidant, we investigated its potentiating effect in autoclaved Leishmania major (ALM)-induced protection of Leishmania major-infected BALB/c. METHODS: First, BALB/c mice were sensitized for 6 weeks either with CA, or ALM alone or combined with caffeic acid (ALM-CA) or Freund's adjuvant (ALM-FA), and subsequently infected with L. major promastigotes. Second, to test the curative effect, CA was given daily for 5 weeks to susceptible mice, starting on week 4 post-infection. Sera, footpads and lymph nodes (LNs) were collected at week 9 post-infection and submitted to biochemical or histological analyses. RESULTS: Compared to the respective controls, our results showed that CA directly healed footpad lesions and reduced the hallmarks of cutaneous leishmaniasis including oxidative inflammation, parasite load, and phagocytes influx and infestation. In sensitized mice, the protection enhanced gradually from ALM-FA, CA, ALM to ALM-CA in parallel to decreased seric IgGt levels. In contrast to ALM-FA, the combined effect of ALM and CA increased specific isotype IgG2, and decreased IL-17 and MCP-1, and phagocyte influx, as attested by the concomitant reduction in myeloperoxidase (MPO) and α-naphthyl acetate esterase (ANAE) activities. ALM-CA shifted IFN-γ/TGF-ß and iNO synthase/arginase1 (iNOS/Arg1) balances in a Th1 immune response that control efficiently cutaneous lesions and LNs hypertrophy, and reactivate the death of infected phagocytes. CONCLUSIONS: Therefore, CA combined with ALM synergizes with L. major antigens for priming innate cells, through early polarization to optimal Th1 response that leads to IFN-γ and iNOS-dependent leishmanicidal activity of neutrophils and macrophages.

A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system.

While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders.

4,5,4'-Trihydroxychalcone, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol and rutin from Gynura segetum inhibit phagocytosis, lymphocyte proliferation, cytokine release and nitric oxide production from phagocytic cells.

BACKGROUND: Gynura segetum is used traditionally to treat various ailments related to the immune system, which include cancer, inflammation, rheumatism, diabetes, hypertension, and viral infections but little studies have been carried out to validate their ethnopharmacological aspects. In this study the immunosuppressive effects of G. segetum and its constituents were investigated. METHODS: Isolation of compounds from G. segetum leaves was conducted using vacuum liquid chromatography (VLC) and column chromatography (CC). Two new compounds, namely 4,5,4'-trihydroxychalcone and 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol, together with stigmasterol and ß-sitosterol were isolated from G. segetum methanol extract and their structures were determined spectroscopically. The presence of gallic acid and rutin in the extract was determined quantitatively by a validated HPLC method. G. segetum methanol extract and its constituents were investigated for their effects on chemotaxis, phagocytosis, ß2 integrin (CD18) expression, and reactive oxygen species (ROS) of polymorphonuclear leukocytes (PMNs), lymphocytes proliferation, cytokine release and nitric oxide (NO) production of phagocytes. RESULTS: All the samples significantly inhibited all the innate immune responses tested except CD 18 expression on surface of leukocytes. Among the samples, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol exhibited the strongest inhibitory on chemotaxis, phagocytosis, ROS and NO production. The compound exhibited exceptionally strong inhibitions on ROS and chemotaxis activities with IC50 values lower than the positive controls, aspirin and ibuprofen, respectively. 4,5,4'-Trihydroxychalcone revealed the strongest immunosuppressive activity on proliferation of lymphocytes (IC50 value of 1.52 µM) and on release of IL-1ß (IC50 value of 6.69 µM). Meanwhile rutin was the most potent sample against release of TNF-α from monocytes (IC50, 16.96 µM). CONCLUSION: The extract showed strong immunosuppressive effects on various components of the immune system and these activities were possibly contributed mainly by 4,5,4'-trihydroxychalcone, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol and rutin.

Chemical composition and phagocyte immunomodulatory activity of Ferula iliensis essential oils.

Essential oil extracts from Ferula iliensis have been used traditionally in Kazakhstan for treatment of inflammation and other illnesses. Because little is known about the biologic activity of these essential oils that contributes to their therapeutic properties, we analyzed their chemical composition and evaluated their phagocyte immunomodulatory activity. The main components of the extracted essential oils were (E)-propenyl sec-butyl disulfide (15.7-39.4%) and (Z)-propenyl sec-butyl disulfide (23.4-45.0%). Ferula essential oils stimulated [Ca2+]i mobilization in human neutrophils and activated ROS production in human neutrophils and murine bone marrow phagocytes. Activation of human neutrophil [Ca2+]i flux by Ferula essential oils was dose-dependently inhibited by capsazepine, a TRPV1 channel antagonist, indicating that TRPV1 channels mediate this response. Furthermore, Ferula essential oils stimulated Ca2+ influx in TRPV1 channel-transfected HEK293 cells and desensitized the capsaicin-induced response in these cells. Additional molecular modeling with known TRPV1 channel agonists suggested that the active component is likely to be (Z)-propenyl sec-butyl disulfide. Our results provide a cellular and molecular basis to explain at least part of the beneficial therapeutic properties of FEOs.

Anti-diabetic effect of the ethyl acetate fraction of Clerodendrum volubile: protocatechuic acid suppresses phagocytic oxidative burst and modulates inflammatory cytokines.

The antidiabetic effects of the ethyl acetate (EtOAc) fraction of Clerodendrum volubile leaves was investigated in this study. EtOAc extract was also fractionated to isolate the active compounds. The structure of the isolated compound (Protocatechuic acid) was established using 1H and 13C NMR spectroscopies and mass spectrometry. Protocatechuic acid was investigated for its anti-oxidative burst in polymorphonuclear neutrophils (PMNs) and macrophages. It was also docked with α-glucosidase and TNF-α. Acute treatment with EtOAc fraction of Clerodendrum volubile leaves significantly (p<0.05) decreased blood glucose level and hepatic biomarkers, and significantly (p<0.05) increased serum insulin level and ß-cell function. It had little or no effect on serum lipid profile and atherogenic indices. Protocatechuic acid significantly (p<0.05) suppressed phagocytic oxidative burst and docked well with α-glucosidase and TNF-α. These results indicate the therapeutic effect of EtOAc fraction of C. volubile on type 2 diabetes and its complications, which can be attributed to the main bioactive compound, protocatechuic acid.

Sideritis spp. Extracts Enhance Memory and Learning in Alzheimer's ß-Amyloidosis Mouse Models and Aged C57Bl/6 Mice.

Nowadays, Alzheimer's disease is the most prevalent epiphenomenon of the aging population. Although soluble amyloid-ß (Aß) species (monomers, oligomers) are recognized triggers of the disease, no therapeutic approach is able to stop it. Herbal medicines are used to treat different diseases in many regions of the world. On the Balkan Peninsula, at the eastern Mediterranean Sea, and adjacent regions, Sideritis species are used as traditional medicine to prevent age-related problems in elderly. To evaluate this traditional knowledge in controlled experiments, we tested extracts of two commonly used Sideritis species, Sideritis euboea and Sideritis scardica, with regard to their effects on cognition in APP-transgenic and aged, non-transgenic C57Bl/6 mice. Additionally, histomorphological and biochemical changes associated with Aß deposition and treatment were assessed. We found that daily oral treatment with Sideritis spp. extracts highly enhanced cognition in aged, non-transgenic as well as in APP-transgenic mice, an effect that was even more pronounced when extracts of both species were applied in combination. The treatment strongly reduced Aß42 load in APP-transgenic mice, accompanied by increased phagocytic activity of microglia, and increased expression of the α-secretase ADAM10. Moreover, the treatment was able to fully rescue neuronal loss of APP-transgenic mice to normal levels as seen in non-transgenic controls. Having the traditional knowledge in mind, our results imply that treatment with Sideritis spp. extracts might be a potent, well-tolerated option for treating symptoms of cognitive impairment in elderly and with regard to Alzheimer's disease by affecting its most prominent hallmarks: Aß pathology and cognitive decline.

Inhibitory effects of compounds from Phyllanthus amarus on nitric oxide production, lymphocyte proliferation, and cytokine release from phagocytes.

Standardized extract of Phyllanthus amarus has previously been shown to have a strong inhibitory effect on phagocytic activity of human neutrophils. The current study was carried out to evaluate the effects of constituents of the extract of P. amarus on nitric oxide (NO) production as well as lymphocyte proliferation and cytokine release from phagocytes. Three compounds, ethyl 8-hydroxy-8-methyl-tridecanoate, 7ß,19α dihydroxy-urs-12-ene, and 1,7,8-trihydroxy-2-naphtaldehyde, together with seven known compounds were isolated from the whole plant of P. amarus. The isolated compounds and reference standards, ie, gallic acid, ellagic acid, corilagin, and geraniin, which were quantitatively analyzed in the extracts, were evaluated for their effects on immune cells. Among the compounds tested, the lignans, especially phyltetralin and phyllanthin, showed strong inhibition on lymphocyte proliferation with half maximal inhibitory concentration (IC50) values of 1.07 µM and 1.82 µM, respectively. Ethyl 8-hydroxy-8-methyl-tridecanoate and 1,7,8-trihydroxy-2-naphtaldehyde exhibited strong inhibition on nitric oxide production with IC50 values of 0.91 µM and 1.07 µM, respectively. Of all the compounds, corilagin was the strongest inhibitor of tumor necrosis factor-α release with an IC50 value of 7.39 µM, whereas geraniin depicted the strongest inhibitory activity on interleukin-1ß release with an IC50 value of 16.41 µM. The compounds constituting the extract of P. amarus were able to inhibit the innate immune response of phagocytes at different steps.

Astragaloside IV protects against polymicrobial sepsis through inhibiting inflammatory response and apoptosis of lymphocytes.

BACKGROUND: Sepsis is a major clinical challenge in modern medicine, representing one of the leading causes of death in developed countries. The syndrome is a consequence of a dysregulated immune response, including early uncontrolled systemic inflammation and prolonged immunosuppression in the late phase. The present study was conducted to investigate the therapeutic effects of astragaloside IV (ASI-IV) on the cecal ligation and puncture (CLP)-induced sepsis in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into sham control + vehicle, CLP + vehicle, and CLP + ASI-IV groups. ASI-IV (3 mg/kg) was intravenously injected 1 h after CLP surgery. Survival rate, bacterial clearance, inflammatory mediators, phagocytes emigration, histopathology, and lymphocyte apoptosis were examined. The effects of ASI-IV on peritoneal macrophage activation and its underlying mechanisms were also evaluated. RESULTS: We reported that treatment with ASI-IV significantly improved survival in septic mice. In agreement with this protective effect, the pathologic damage that was typically seen in lung and spleen was ameliorated; the level of bacterial burden was lessened; inflammatory cytokines and chemokines in circulation were profoundly reduced; lymphocyte apoptosis was inhibited. ASI-IV suppressed LPS-induced macrophage activation through inhibiting NF-κB and ERK1/2 signaling pathways. CONCLUSIONS: ASI-IV protected mice against polymicrobial sepsis by inhibiting inflammatory response and lymphocyte apoptosis. Therefore, ASI-IV might provide a novel therapeutic approach for septic patients.

Nanoparticles of barium induce apoptosis in human phagocytes.

PURPOSE: Nutrients and immunological factors of breast milk are essential for newborn growth and the development of their immune system, but this secretion can contain organic and inorganic toxins such as barium. Colostrum contamination with barium is an important issue to investigate because this naturally occurring element is also associated with human activity and industrial pollution. The study evaluated the administration of barium nanoparticles to colostrum, assessing the viability and functional activity of colostral mononuclear phagocytes. METHODS: Colostrum was collected from 24 clinically healthy women (aged 18-35 years). Cell viability, superoxide release, intracellular Ca(2+) release, and phagocyte apoptosis were analyzed in the samples. RESULTS: Treatment with barium lowered mononuclear phagocyte viability, increased superoxide release, and reduced intracellular calcium release. In addition, barium increased cell death by apoptosis. CONCLUSION: These data suggest that nanoparticles of barium in colostrum are toxic to cells, showing the importance of avoiding exposure to this element.

Evaluating the effect of oral administration of Echinacea hydroethanolic extract on the immune system in dog.

This study was designed to evaluate the effects of oral administration of Echinacea hydroethanolic extract on the dog's immune system. The study was performed on 14 dogs that were referred to the veterinary clinic. These dogs were randomly allocated to two equal treatment groups. The first group received 1 ml of 5% Echinacea hydroethanolic extract two times a day for 2 months, and the second group received a placebo (water). To do haematology and immunology tests, the dogs were bled on days 0, 30 and 60. Blood tests, including packed cell volume (PCV), haemoglobin (Hb), red blood cell count (RBC), white blood cell count (WBC), counting neutrophils (Nut), lymphocytes (Lym), monocytes (Mon), eosinophils (Eos), basophils (Baso) and B cell, were performed. Furthermore, safety factor IgM and per cent of phagocytosis and phagocyte were measured from the blood sample. The results showed that in the group which received Echinacea PCV, Hb, RBC count, WBC count, Lym, Nut, the per cent of phagocytosis and IgM significantly increased (P < 0.05). Moreover, positive effects of Echinacea plant on the immune system were observed. There was a significant change in HTC, RBC, Hb over time in the group that received Echinacea and the per cent of phagocytosis and IgM (P < 0.05). The study establishes that these extracts might have appreciable immunostimulatory activity. However, further studies are required to confirm these findings.