Showing papers in "Immunopharmacology and Immunotoxicology in 2011"

Biomarkers of oxidative stress in ruminant medicine

Abstract: The study of oxidative stress is a relatively young field of research in ruminant medicine. Oxidative stress results from increased exposure to or production of oxidants, or from decreased dietary intake, de novo synthesis or increased turnover of antioxidants. The understanding of the role of oxidants and antioxidants in physiological and pathological conditions is rapidly increasing. Oxidative stress is an active field of research in veterinary medicine and has been implicated in numerous disease processes including sepsis, mastitis, acidosis, ketosis, enteritis, pneumonia, respiratory, and joint diseases. Compared to human medicine, only a limited number of conditions have been investigated in regard to the effects of oxidative stress in ruminants. Studies in cattle have been sporadic and mainly with mastitis, pneumonia, and retained placenta. More recently, studies have been focused on metabolic diseases that affect dairy cows during the peripartum period. Numerous and rapidly evolving methodologies for evaluating oxidative stress are available to researchers and clinicians, each with their own distinct advantages and disadvantages. Differences in models and methodologies make it difficult to make meaningful comparisons, even for studies that seem quite similar superficially. With this in mind, it is the goal of this review to discuss the advantages and shortfalls of different methodologies commonly used to measure oxidative stress and damage in ruminants. Clarity of understanding of the pathophysiology of oxidative stress in ruminants will allow the design of specific antioxidant therapies. Future research should focus on the establishment of a reference panel of biomarker of oxidative stress to be used in ruminant medicine. To help accelerate practical applications, we propose the development of an oxidative stress index as an approach in ruminant and veterinary medicine.

All trans retinoic acid and cancer.

Abstract: All-trans retinoic acid (ATRA) is an active metabolite of vitamin A under the family retinoid. Retinoids, through their cognate nuclear receptors, exert potent effects on cell growth, differentiation and apoptosis, and have significant promise for cancer therapy and chemoprevention. Differentiation therapy with ATRA has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). Conversions of 13-cis-retinoic acid and 9-cis-retinoic acid to all-trans-retinoic acid is very rapid. Currently, two distinct families of retinoid responsive nuclear receptors have been identified and characterized: retinoic acid receptors (RARs) and retinoid receptors (RXRs), each of which include three isoforms, α,β,and γ. ATRA is being increasingly included in anti-tumour therapeutical schemes for the treatment of various tumoral diseases such as Kaposi's sarcoma, head and neck squamous cell carcinoma, ovarian carcinoma, bladder cancer, neuroblastoma and has shown antiangiogenic effects in several systems, inhibiting proliferation in vascular smooth muscle cells (VSMCs) and anti-inflammatory in rheumatoid arthritis. This review helps to understand in details about the ATRA and its role on cancer and it is predicted that modulating the activity of ATRA will soon provide novel prevention and treatment approaches for the cancer patients.

Vanillic acid inhibits inflammatory mediators by suppressing NF-κB in lipopolysaccharide-stimulated mouse peritoneal macrophages.

Abstract: Vanillic acid is a benzoic acid derivative that is used as a flavoring agent. It is an oxidized form of vanillin. At present, the mechanisms by which vanillic acid exerts its anti-inflammatory effects are incompletely understood. In this study, we attempted to determine the effects of vanillic acid on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. Our findings indicate that vanillic acid inhibits LPS-induced production of tumor necrosis factor (TNF)-α and interleukin (IL)-6. During the inflammatory process, the levels of cyclooxygenase (COX)-2 and nitric oxide (NO) increased in mouse peritoneal macrophages, but vanillic acid suppressed both the enhanced levels of COX-2 and the production of prostaglandin E(2) and NO. Moreover, vanillic acid suppressed the activation of nuclear factor-kappa B (NF-κB) and caspase-1. These results provide novel insights into the pharmacological actions of vanillic acid and are indicative of the potential use of this molecule in the treatment of inflammatory diseases.

Oral lichen planus: update on etiopathogenesis, diagnosis and treatment

Abstract: Lichen planus is an inflammatory mucocutaneous disorder. Skin, oral and genital mucosal surfaces, scalp, and nails can be affected. Its development is chronic, with a possible malignant degeneration. Spontaneous remission is rare. Although the etiology of oral lichen planus is still unclear, there is evidence that it is a complex immunologic disease mediated by cytotoxic cells directed against basilar keratinocytes and resulting in vacuolar degeneration and lysis of basal cells. In long-standing, atrophic and erosive forms, the treatment is usually aimed at relieving pain and may include immunosuppressive agents, especially corticosteroid, topical cyclosporin, or tacrolimus, topical and systemic retinoids. However, the use of these drugs may be accompanied by several side effects. For this reason clinicians, currently, have focused their attention to new biological agents which provide selective immunological results with less side effects than generic immunosupressants.

In vitro toxicity of silver nanoparticles on murine peritoneal macrophages.

Abstract: Silver nanoparticles, the new generation of antimicrobial agents, are becoming one of the progressively growing products in nanotechnology. Meanwhile, the potential side effects of these nanoparticles have not been studied thoroughly yet. Macrophages, one of the most important immune cells in innate and acquired immune responses, are a key component of the clearance mechanisms in semi-open interfaces of human body against nanosilver (nano-Ag). In this experimental study, we assessed the effect of commercial colloidal nano-Ag on murine peritoneal macrophages by MTT and nitric oxide (NO) production assay in vitro. A significant decrease in cell viability was observed for 1 ppm (part per million) to 25 ppm of nano-Ag concentrations compared to the control group (P < 0.01) after 24 h of cell culture. Also, a significant decrease in the cell viability was observed for 2–25 ppm of nano-Ag concentrations after 48–72 h, respectively (P < 0.05). In our study, exposure to 0.4–25 ppm of colloidal nano-Ags brought ab...

The regulatory mechanism of β-eudesmol is through the suppression of caspase-1 activation in mast cell-mediated inflammatory response

Abstract: β-Eudesmol is sesquiterpenoid alcohol which contains the rhizome of Atractylodes lancea. Although it has multiple pharmacological effects, the anti-inflammatory effect of β-eudesmol and its molecular mechanisms are poorly elucidated. In this study, we investigated the regulatory mechanism of β-eudesmol on mast cell-mediated inflammatory response. The results indicated that β-eudesmol inhibited the production and expression of interleukin (IL)-6 on phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated human mast cell (HMC). In activated HMC-1 cells, β-eudesmol suppressed activation of p38 mitogen-activated protein kinase (MAPKs) and nuclear factor-κB. In addition, β-eudesmol suppressed the activation of caspase-1 and expression of receptor-interacting protein-2. These results provide new insights into the pharmacological actions of β-eudesmol as a potential molecule for use in therapy in mast cell-mediated inflammatory diseases.

Apigenin inhibits release of inflammatory mediators by blocking the NF-κB activation pathways in the HMC-1 cells

Abstract: Apigenin is a plant flavonoid and a pharmacologically active agent that has been isolated from several plant species. However, the molecular mechanism of apigenin-mediated immune modulation has not been fully understood. One of the possible mechanisms of its protective effects is the down-regulation of inflammatory responses. In this study, we used cells from the human mast cell line (HMC-1) to investigate this effect. Apigenin significantly inhibits the inductive effect of phorbol 12-myristate 13-acetate (PMA) plus A23187 on the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-6, and granulocyte–macrophage colony-stimulating factor (GM-CSF). Moreover, apigenin attenuated the cyclooxygenase (COX)-2 expression and intracellular Ca2+ level. In activated HMC-1 cells, apigenin inhibited the PMA plus A23187-induced activation of nuclear factor (NF)-κB, IκB degradation, and luciferase activity. Furthermore, apigenin suppressed the expression of TNF-α, IL-8, IL-6...

Regulatory T-cell as orchestra leader in immunosuppression process of multiple sclerosis.

Abstract: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system characterized by perivascular inflammation and demyelination and loss of neurologic function. In this disease and its experimental model (experimental autoimmune encephalomyelitis, EAE), axonal and neuronal loss is thought to play a key role in irreversible loss of function and disability. Regarding the evident role of autoreactive T-cells (particularly Th1 and Th17 cells) in pathophysiology of MS, it might be assumed that the regulatory T-cells (Tregs) can control initiation and progression of disease and even treat it. The frequency, function and properties of various subsets of Tregs including natural Tregs (nTregs), IL-10 producing type 1 Tregs (Tr1 cells), transforming growth factor-β producing Th3 cells, CD8+ Tregs, and natural killer like T regulatory cells in MS and its model EAE, have been investigated in several experimental studies. In this review, we intend to submit the comprehensive information...

Evaluation of immunomodulatory effect of three herbal plants growing in Egypt

Abstract: A group of medicinal plant including Silene (Silene nocturna), Black seed (Nigella sativa) and Chamomile (Matricaria chamomilla) growing in Egypt were examined for their immunomodulatory effect in Balb/c mice. Treatment (intraperitoneal injection) with five doses of methanolic extract for each plant was found to enhance the total white blood cells count (up to 1.2 × 104 cells/mm3). Bone marrow cellularity also increased significantly (P < 0.01) after the administration of the extract of each of three test plants. Furthermore, spleen weight of the treated groups was significantly increased (P < 0.01). Two groups of mice were immunosuppressed with cyclophosphamide, the one which pretreated with the plants extracts significantly (P < 0.01) restored their resistance against lethal infection with the predominately granulocyte-dependant Candida albicans. These results confirm the immunomodulatory activity of Silene, Black seed, and Chamomile extracts and may have therapeutical implications in prophylactic treat...

Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation

Abstract: Context: Cinnamon bark is a very popular herb used in traditional medicine to treat various disorders such as chronic gastric symptoms, arthritis, and the common cold.Objective: The immunomodulatory effect of water extract of cinnamon bark (CWE) on cytokine secretion and involvement of intracellular signaling molecules in activated T cells have been examined.Materials and methods: Mice were orally administered CWE for 7 days. Serum was obtained 90 min after intravenous injection of anti-CD3 antibody (Ab). Splenocytes were cultured with anti-CD3 Ab and CWE for cytokine expression, cell cycle, apoptotic/necrotic changes, and viability. IκBα, p38, JNK, ERK1/2, STAT4, and STAT6 were analyzed using western blotting.Results: Administration of CWE decreased systemic levels of IFN-γ, but not the levels of IL-4 or IL-2. In vitro, CWE inhibited anti-CD3 Ab-stimulated IFN-γ and IL-4 at the mRNA and secreted protein levels. Despite its inhibition of IL-2 transcript, CWE enhanced IL-2 secretion. CWE treatment caused a...

Modulation of immune response by Vernonia cinerea L. inhibits the proinflammatory cytokine profile, iNOS, and COX-2 expression in LPS-stimulated macrophages.

Abstract: The effect of methanolic extract of Vernonia cinerea L. on the immune system was studied using BALB/c mice. Intraperitoneal (i.p.) administration of five doses of the extract (20 mg/kg body weight) was found to enhance the total white blood cell (WBC) count (13,700 ± 463 cells/mm3) on 6th day, bone marrow cellularity (27.9 ± 2.1 × 106 cells/femur) and number of α-esterase positive cells (1184 ± 56.29/4000 cells). Treatment with V. cinerea along with the antigen, sheep red blood cells (SRBC), produced an enhancement in the circulating antibody titre and the number of plaque forming cells (PFC) in the spleen. Maximum number of PFC (304.16 ± 12.4) was obtained on the 6th day. It also enhanced the proliferation of splenocytes, thymocytes and bone marrow cells both in the presence and absence of specific mitogens in vitro and in vivo. Administration of V. cinerea significantly reduced the lipopolysaccharide (LPS) induced elevated levels of nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis ...

Immunomodulation of experimental allergic encephalomyelitis by cinnamon metabolite sodium benzoate.

Abstract: Experimental allergic encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), the most common human demyelinating disease of the central nervous system. Sodium benzoate (NaB), a metabolite of cinnamon and a FDA-approved drug against urea cycle disorders in children, is a widely used food additive, which is long known for its microbicidal effect. However, recent studies reveal that apart from its microbicidal effects, NaB can also regulate many immune signaling pathways responsible for inflammation, glial cell activation, switching of T-helper cells, modulation of regulatory T cells, cell-to-cell contact, and migration. As a result, NaB alters the neuroimmunology of EAE and ameliorates the disease process of EAE. In this review, we have made an honest attempt to analyze these newly-discovered immunomodulatory activities of NaB and associated mechanisms that may help in considering this drug for various inflammatory human disorders including MS as primary or adjunct therapy.

Protective effects of quercetin and chrysin against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative stress, body wasting and altered cytokine productions in rats.

Abstract: The aim of this study is to investigate the effects of the quercetin (Q) and chrysin (CH) on oxidative stress, cytokines levels and body weights in rats induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were divided randomly into six equal groups. TCDD, Q and CH were administered by gavages dissolved in corn oil at the doses of 2 µg/kg/week, 20 mg/kg/day and 50 mg/kg/day, respectively. The blood samples were taken from all rats at 60th days to be analyzed for the determination of thiobarbituric acid reactive substances (TBARS), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The results indicated that although TCDD increased significantly TBARS and TNF-α levels, it caused a decline in the levels of IFN-γ and body weight. In contrast, these effects of TCDD on TBARS, TNF-α, IFN-γ levels and body weight were significantly prevented by treatments of Q and CH. In conclusion, it was determined that TCDD caused the adverse effects on immune functions, body weight and oxidative stress in rats....

Effect of anionic and cationic n-butylcyanoacrylate nanoparticles on NO and cytokine production in Raw264.7 cells.

Abstract: Context: Research on drug delivery carriers that use nanoparticles is currently attracting a great deal of attention. In order to evaluate the safety of these drug carriers for clinical applications, a full assessment of their toxicity and bioactivity is required. Although it is well-known that the surface charge of nanoparticles influences their bioactivity, most of the published studies on n-butylcyanoacrylate (NBCA) nanoparticles as a potential drug delivery carrier are restricted to analyzing the anionic form.Objective: We compared biological responses of cyanoacrylate anionic nanoparticles with cationic nanoparticles in cultured murine macrophages for assessing cytotoxicity and inflammatory responses.Materials and methods: The cytotoxicity was evaluated with the MTS and LDH leakage assays. Inflammatory responses were evaluated by measurement of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The interaction of the nanoparticle and the macrophage was assessed by fluor...

Comparison of major lipid components in human and donkey milk: new perspectives for a hypoallergenic diet in humans

Abstract: Recently, donkey milk has been indicated as a nutraceutical food thanks to some bioactive compounds interesting in the human diet; these substances are the lipids, which are characterized by the ability in conditioning indirectly or directly the intestinal environment and immunity, taking part in the prevention and treatment of some pathologies. With the aim to compare some nutritional properties of human and donkey milk, the triacylglycerol (TAG) composition and the positional isomers of donkey milk samples were analyzed by HPLC-APCI-MS on reversed phase and silver ion columns. The technique allowed the identification of 72 TAGs in the samples analyzed. Similarities and differences among the TAGs fraction of human and donkey milk can be easily determined by HPLC analysis of the lipid fraction. Donkey milk presents TAGs with partition number (PN) values starting from 30 up to 50. In human milk, the short-chain fatty acids (FAs) are not well-represented and the PN values range between 36 and 52. Other significant differences are among TAGs containing polyunsaturated fatty acids (PUFA). In fact, donkey milk presents a larger number and amount of ω3 and ω6 FAs than human milk, which contains only significant amount of ω6 FA (linoleic). Both donkey and human milk present the saturated FA preferably on the sn-2 position. Data testify a certain degree of similarity of these products in relation to their digestibility and confirm the increasing interest toward donkey milk as an alternative food for hypoallergenic diet in humans.

Suppression of inflammatory responses after onset of collagen-induced arthritis in mice by oral administration of the Citrus flavanone naringin.

Abstract: Rheumatoid arthritis (RA) is closely related to the pathogenesis of tumor necrosis factor α in lesions. We investigated the suppressive effects of a Citrus flavanone naringin on inflammatory responses in mice with collagen-induced arthritis (CIA), a mouse model for RA. To investigate potential preventive and therapeutic effects of naringin, mice were given naringin orally three times a week from the second immunization with collagen (day 21) and from day 31, when symptoms of CIA had reached a plateau, respectively. In both cases, inflammation-related clinical scores for knee joints were significantly reduced by administration of naringin. Histological analyses demonstrated that representative phenomena, such as damage to interchondral joints, infiltration of inflammatory cells and pannus formation, were significantly depressed by treatment with naringin. In addition, increases in the expression of high-mobility group box-1 protein in the joints of mice with CIA were suppressed by naringin. These results s...

In vivo and in vitro anti-inflammatory effects of a novel derivative of icariin.

Abstract: Icariin is the major active constituent of Epimedii Herba. Our recent study showed that icariin displayed anti-inflammatory potential. One novel derivate of icariin is 3,5,7-Trihydroxy-4′-methoxy-8-(3-hydroxy-3-methylbutyl)-flavone (ICT). Little is known about ICT’s pharmacological activities. In our study, the anti-inflammatory properties of ICT were evaluated. Murine RAW264.7 cells and C57BL/6J mice stimulated by lipopolysaccharide (LPS) was used as in vitro and in vivo inflammatory model, respectively. Our data showed that ICT (1–100 μg/mL) significantly inhibited LPS-induced tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2) production in vitro. These effects did not depend on cytotoxicity. The in vivo assay displayed that pretreatment of C57BL/6J mice with ICT (25–100 mg/kg, by gavage) for 3 days decreased LPS-induced serum levels of TNF-α, PGE2, and neutrophils CD11b expression dose-dependently. Furthermore, our data suggested that ICT reduced NO and PGE2 levels by inhibitin...

Catechin inhibits adhesion and migration of peripheral blood B cells by blocking CD11b.

Abstract: Context: Previously, we demonstrated that CD11b is expressed on peripheral blood memory B cells, and it plays an important role in the migration of B cells. And epigallocatechin gallate (EGCG), a bioactive component of green tea, by binding to CD11b, expressed on CD8(+) cytotoxic T cells, inhibited their migratory ability, one possible mechanism of the antiallergic activity of EGCG.Objective: Here, we investigated whether EGCG also affected CD11b expressed on B cells, similar to cytotoxic T cells.Materials and methods: Isolated peripheral blood CD19(+) B cells were treated with EGCG and the change in the expression of CD11b was analyzed using flow cytometry. The effects of EGCG on the ability of B cells to adhere to and to transmigrate through the endothelial cell layer were evaluated using the transwell assay.Results: EGCG significantly suppressed the apparent expression of CD11b on B cells, in the flow-cytometric analysis, and this apparent suppression was speculated to be dependent on the competitive b...

Adjuvant effects of salidroside from Rhodiola rosea L. on the immune responses to ovalbumin in mice.

Abstract: Salidroside, a major component of Rhodiola rosea L., was evaluated for its adjuvant effects on the immune responses in mice by ovalbumin (OVA) stimulation. BALB/c mice were immunized subcutaneously with OVA 100 μg or OVA 100 μg dissolved in saline containing alum (100 μg) or salidroside (12.5, 25, or 50 μg) on Days 1 and 15. Two weeks later (Day 28), blood samples were collected to analyze OVA-specific IgG, IgG1, and IgG2b antibodies. Meanwhile, splenocytes were harvested to assess lymphocyte proliferation, cytokines (IL-2, IL-4, and IFN-γ) production, and CD4+, CD8+ lymphocyte subsets. The results indicated that co-administration of salidroside with OVA significantly enhanced the ConA-, LPS-, and OVA-induced splenocyte proliferation, produced more IL-2, IL-4, IFN-γ, and IgG, IgG1, and IgG2b antibody levels, and increased the percentage of CD4+, CD8+ lymphocyte subsets than OVA alone. Thus, salidroside possess immunological adjuvant activity by regulating humoral and cellular immune responses in mice.

Enhancement of the immunogenicity of DNA replicon vaccine of Clostridium botulinum neurotoxin serotype A by GM-CSF gene adjuvant

Abstract: Granulocyte-macrophage clony-stimulating factor (GM-CSF) is an attractive adjuvant for a DNA vaccine on account of its ability to recruit antigen-presenting cells to the site of antigen synthesis as well as stimulate the maturation of dendritic cells.This study evaluated the utility of GM-CSF as a plasmid DNA replicon vaccine adjuvants for botulinum neurotoxin serotype A (BoNT/A) in mouse model. In balb/c mice that received the plasmid DNA replicon vaccines derived from Semliki Forest virus (SFV) carrying the Hc gene of BoNT/A (AHc), both antibody and lymphoproliferative response specific to AHc were induced, the immunogenicity was enhanced by co-delivery or coexpress of the GM-CSF gene. In particular, when AHc and GM-CSF were coexpressed within the SFV based DNA vaccine, the anti-AHc antibody titers and survival rates of immunized mice after challenged with BoNT/A were significantly increased, and further enhanced by coimmunization with aluminum phosphate adjuvant.

The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis.

Abstract: Inflammatory bowel diseases are characterized by disabilities in gastrointestinal system and defects in mucosal immune system. Statins are 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor...

Immunomodulatory effects of Aloe vera and its fractions on response of macrophages against Candida albicans.

Abstract: Natural products are important resources in traditional medicine and have been long used for prevention and treatment of many diseases. Medicinal plants have immunomodulatory properties. Aloe is one of the herbal medicines widely used in natural treatment and alternative therapy for various types of diseases. Aloe vera has been shown to modulate the immune response. Macrophages have been shown to play an essential role as the first line of defense against invading pathogen. Candida albicans is a communal and opportunistic pathogen in humans. In this study, we investigated the effect of A. vera extract and its fractions on infected macrophages with C. albicans. Viability of intraperitoneal macrophages was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Cell viability of infected macrophages was increased by the extract and dose of some isolated fractions dependently. The extract as well as R100, R50, R30, and R10 fractions of A. vera significantly increased cell viability of macrophages in most doses. R5 and F5 fractions showed no significant difference in comparison with control group. Further studies in animal models and human are necessary to clarify the modulatory effects of A. vera on macrophage function. Isolation and purification of A. vera components are also needed to find out the effective molecules.

Inhibition of tumor cells growth and stimulation of lymphocytes by Euphorbia species

Abstract: Plants have been shown to possess a number of beneficial anticancer and immunomodulatory properties. In this study the possible in vitro antitumor activity and immunomodulatory effects of five species of Euphorbia, an important genus of Euphorbiaceae, including E. petiolata, E. hebecarpa, E. osyridea, E. microciadia, and E. heteradenia were investigated using cytotoxicity and cell proliferation assays. Among different tumor cell lines, the most sensitive cell line to methanolic extracts of the plants was determined as follows. Hela cervical cancer cells to E. hebecarpa and E. microciadia, K562 leukemia cells to E. petiolata and E. heteradenia, and Fen bladder cancer cells to E. osyridea. The methanolic extracts were then fractionated into hexane, n-butanol, ethyl acetate, and water and the effect of these fractions was tested for cytotoxic activity on the selected cell lines. The results indicated the significant stronger antiproliferatory effect of the hexane factions in all the plants when compared with other ones. The methanolic extracts of the plants were also studied for their effects on the activation of the lymphocytes. All of the extracts showed stimulatory effects on the proliferation of the lymphocytes at lower concentrations. After further fractionation of the extracts, the butanolic and hexane fractions showed the highest activity on the lymphocyte activation. In conclusion, all the plants studied had the capacity to inhibit proliferation of tumor cells with beneficial immunomodulatory effects on the lymphocytes. This dual effect of the plants indicates their value for further investigations as antitumor agents.

Emodin-induced microglial apoptosis is associated with TRB3 induction

Abstract: Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a natural anthraquinone compound isolated from the rhizome of rhubarb, has been reported to treat brain injury after intracerebral hemorrhage. Treatment of neurons with emodin is able to decrease glutamate excitotoxicity, modulate calcium homeostasis, and induce Bcl-2 expression. However, the effects of emodin on the brain-resident innate immune cells are unclear. In the present study, the mouse microglial cell line, BV-2, was selected to investigate the effects of emodin on microglial activation and apoptosis. Cell viability and apoptosis were sequentially measured with the CellTiter-Glo Luminescent Cell Viability Assay, YOPRO-1 and Caspase-Glo 3/7 Assay Systems. The degree of microglial activation was evaluated using quantitative RT-PCR to measure expression of inflammatory markers. Treatment of BV-2 cells with emodin caused caspase-mediated apoptosis in a dose-dependent manner, and emodin augmented LPS-induced microglial apoptosis to repress inflammatory activation. In response to emodin treatment, reactive oxygen species (ROS) production was increased, and TRB3 was markedly activated. siRNA knockdown of TRB3 attenuated emodin-induced microglial apoptosis. Ectopic overexpression of TRB3 decreased cell viability and was associated with dysregulation of the prosurvival Akt/FOXO3 pathway. These results demonstrate that emodin induces BV-2 cell apoptosis through TRB3 and consequently eliminates inflammatory microglia. Our findings provide a novel molecular basis through which emodin exerts neuroprotective effects, treating brain injury after intracerebral hemorrhage.

Immunomodulatory and antitumor activity of Aerva lanata ethanolic extract.

Abstract: Cancer is responsible for millions of deaths each year worldwide. Pharmacological intervention with plant-derived products alone or in combination to reverse, suppress, or prevent the cancer progression plays a key role in the fight against this terrible disease. Aerva lanata is an important medicinal plant widely used in traditional systems of medicine like ayurveda and siddha. Ethanolic extract of whole plant of A. lanata exhibited immunomodulatory and antitumor activity. Intraperitoneal administration of five doses of the extract (10 mg/kg body weight) was found to enhance the total WBC count (14,238 cells/mm3), bone marrow cellularity (22.33 × 106 cells/femur), and number of α-esterase-positive cells (1276 cells/4000 cells). Aerva treatment also showed enhanced proliferation of splenocytes, thymocytes, and bone marrow cells both in the presence and absence of specific mitogens in vitro and in vivo. The number of plaque-forming cells (PFC) in spleen (243.33 PFC/106 spleen cells) and circulating antibod...

Protective effects of Wu-Ling-Shen (Xylaria nigripes) on carbon tetrachloride-induced hepatotoxicity in mice

Abstract: Wu-Ling-Shen, a lesser study medicinal fungus (Xylaria nigripes), is popular for treating insomnia and trauma in the traditional Chinese medicine. In this study, our aim was to examine the protective effects of X. nigripes extract on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in mice, and its content of polyphenolic constituents. The X. nigripes aqueous extract (XN-T) at 500 and 1000 mg/kg was given intragastrically to mice for 9 consecutive days, followed by receiving subcutaneously 2 mL/kg of 40% CCl4 in olive oil to induce hepatotoxicity. Blood and liver tissues were collected for biochemical and histological analyses. Analysis of polyphenolic compounds was performed by RP-HPLC. Results showed that XN-T at 500 and 1000 mg/kg significantly prevented the elevation of serum glutamate oxalate transaminase (sGOT), serum glutamate pyruvate transaminase (sGPT), and liver thiobarbituric acid reactive substances (TBARS) levels, and caused an increase in the liver superoxide dismutase (SOD), catala...

Major whey proteins in donkey's milk: effect of season and lactation stage. Implications for potential dietary interventions in human diseases

Abstract: According to current literature, donkey’s milk has been suggested as a hypoallergenic substitute in children affected by cow’s milk protein allergy as well as a promising nutraceutical for aged people. However, the biologically active components of donkey’s milk have not yet completely elucidated. In this framework this study is aimed at measuring α-lactalbumin (α-LA), β-lactoglobulin (β-LG), and lysozyme (LYS), the principal whey proteins in donkey’s milk, in relation to lactation stage and production season. Analysis were performed by reversed-phase high-performance liquid chromatography. α-LA, β-LG, and LYS resulted to be affected by lactation stage (P P < 0.05) during the first four lactation’s months and decreased until the month 8. The β-LG was the major protein (1.75 mg mL−1 as mean; peak 2.24 ± 0.09 mg mL−1), while the α-LA had a mean concentration of 1.32 mg mL−1 and peaked at month 1 (1.57 ± 0.09 mg mL−1) a...

Leaf extracts from Phlomis crinita Cav. subs. mauritanica Munby affect immune cell functions in vitro

Abstract: Aqueous and methanolic leaf extracts from Phlomis crinita subs. mauritanica Munby were investigated for their potential immunomodulatory activity on mouse lymphocytes and macrophages in vitro. The phagocytic activity of macrophages and the proliferation of lymphocytes in the absence and presence of mitogens (lipopolysaccharide, LPS or lectin) were assayed. Depending on the concentrations, the extracts affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide release. For lymphocyte proliferation assay, both extracts enhance significantly cell proliferation either with or without mitogen stimulation. These results suggest that leaf extracts from P. crinita subs. mauritanica Munby contain potent components such as flavonoids that potentially may be useful for modulating immune cell functions in physiological and pathological conditions.

p38-targeted inhibition of interleukin-12 expression by ethanol extract from Cordyceps bassiana in lipopolysaccharide-activated macrophages.

Abstract: Cordyceps species have been known as ethnopharmacologically valuable mushroom in Korea, China, and Japan. This plant has been reported to exhibit a variety of pharmacological activities such as antioxidative, anticancer, anti-inflammatory, antidiabetic, and antiobesity effects. Although numerous pharmacological potentials of Cordyceps spp. have been demonstrated, immunomodulatory effect of Cordyceps bassiana has not been published yet. To evaluate its immunomodulatory activity, macrophages activated by lipopolysaccharide (LPS) were employed and the production of interleukin-12 (IL-12) was explored in terms of understanding its molecular inhibitory mechanism. Seventy percent of ethanol extract from Cordyceps bassiana (Cb-EE) was able to suppress the expression of IL-12, a cytokine regulating interferon-γ (IFN-γ)-producing T helper type 1 (Th1) polarization response, at the transcriptional levels. The inhibitory effect of Cb-EE seemed to be due to activator protein-1 (AP-1) translocation inhibition, accordi...

Cholecystokinin octapeptide regulates lipopolysaccharide-activated B cells co-stimulatory molecule expression and cytokines production in vitro.

Abstract: Cholecystokinin octapeptide (CCK8) can exert the immunoregulatory roles through activating immune cell surface receptors such as T lymphocytes, macrophages, dendritic cells, and so on. In this study, we discussed the effects of CCK8 on lipopolysaccharide (LPS)-activated B cells in terms of the expression of co-stimulatory molecules, and the capacity to activate CD4(+) T cells and cytokines production in vitro. The results revealed that B cells expressed two types of CCK receptors; CCK8 inhibited the expression of co-stimulatory molecules such as CD80 and CD86 on LPS-activated B cells, suppressed the proliferation of allogeneic T cells in a dose-dependent manner, and also reduced the secretion of Th1-type cytokine IFN-γ, whereas enhanced the secretion of Th2-type cytokine IL-4 by LPS-activated B cells. Both CCK1R and CCK2R participated in these effects. Taken together, CCK8 is capable of exerting immunomodulatory functions through B cells.