Anti-Inflammatory Activity of Ferula assafoetida Oleo-Gum-Resin (Asafoetida) against TNF-α-Stimulated Human Umbilical Vein Endothelial Cells (HUVECs).

Inflammation is the body's biological reaction to endogenous and exogenous stimuli. Recent studies have demonstrated several anti-inflammatory properties of Ferula species. In this paper, we decided to study the anti-inflammatory effect of ethanolic extract of Ferula assafoetida oleo-gum-resin (asafoetida) against TNF-α-stimulated human umbilical vein endothelial cells (HUVECs). HUVECs were cultured in a flat-bottom plate and then treated with ethanolic extract of asafoetida (EEA, 0-500 µg/ml) and TNF-α (0-100 ng/ml) for 24 h. We used the MTT test to assess cell survival. In addition, the LC-MS analysis was performed to determine the active substances. HUVECs were pretreated with EEA and then induced by TNF-α. Intracellular reactive oxygen species (ROS) and adhesion of peripheral blood mononuclear cells (PBMCs) to HUVECs were evaluated with DCFH-DA and CFSE fluorescent probes, respectively. Gene expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin and surface expression of ICAM-1 protein were measured using real-time PCR and flow cytometry methods, respectively. While TNF-α significantly increased intracellular ROS formation and PBMC adhesion to TNF-α-induced HUVECs, the pretreatment of HUVECs with EEA (125 and 250 µg/ml) significantly reduced the parameters. In addition, EEA pretreatment decreased TNF-α-induced mRNA expression of VCAM-1 and surface protein expression of ICAM-1 in the target cells. Taken together, the results indicated that EEA prevented ROS generation, triggered by TNF-α, and inhibited the expression of VCAM-1 and ICAM-1, leading to reduced PBMC adhesion. These findings suggest that EEA can probably have anti-inflammatory properties.

Alliin alleviates LPS-induced pyroptosis via promoting mitophagy in THP-1 macrophages and mice.

Pyroptosis is a new type of programmed cell death associated with inflammation. Excessive pyroptosis can cause body damage. Alliin is an organosulfur compound extracted from garlic, bearing anti-oxidation and anti-inflammatory properties. In this study, we revealed that alliin alleviated LPS-induced macrophage pyroptosis by detecting PI staining, IL-1ß and IL-18 release in vitro and in vivo. In the study of mechanism, we found that alliin might reduce the activation of NLRP3 inflammosome by decreasing intracellular ROS generation. Subsequently, we detected the effect of alliin on mitophagy which degraded damaged mitochondria. The results showed that alliin promoted PINK 1/Parkin-mediated mitophagy. After adding the mitophagy inhibitor CsA, the alleviating effect of alliin on mitochondrial damage and mitochondrial ROS were reversed and the relieving effect of alliin on LPS-induced pyroptosis was inhibited. These results suggested that alliin might reduce intracellular ROS production by promoting mitophagy, thus alleviating LPS-induced macrophages pyroptosis. Our study provides a new perspective and theoretical basis for alliin to alleviate pyroptosis which could further induce body damage.

Thyme oil alleviates Ova-induced bronchial asthma through modulating Th2 cytokines, IgE, TSLP and ROS.

Bronchial asthma (BA) is a heterogeneous allergic respiratory disease with diverse inflammatory symptoms, pathology, and responses to treatment. Thyme is a natural product which is consisted of multiple phenolic compounds of therapeutic significance for treatment of cough and bronchitis. This study evaluated the efficacy of thyme oil against ovalbumin (OVA)-induced BA in an experimental rabbit model. Forty male rabbits were divided into four equal groups [control group (G1), OVA (G2), thyme oil (G3), and OVA plus thyme oil (G4)]. Animals were treated for 30 days, and clinical, histopathological (HP), histochemical (HC), immunohistochemical (IHC), morphometric, biochemical and flow cytometry methods were performed, followed by statistical analysis. All used methods revealed normal structure of the lung tissues in rabbits of G1 and G3. In contrast, the clinical examination of G2 rabbits revealed an obvious increase in the respiratory rate, sneezing and wheezing, whereas the HP, HC and IHC techniques exhibited substantial inflammatory changes in the peribronchio-vascular lung tissues with thinning, degeneration, apoptosis (using the TUNEL assay), necrosis, and shedding of the airway epithelium. Furthermore, the morphometric results confirmed significant increases in the numbers of inflammatory cells, goblet cells, eosinophils and apoptotic cells from (12, 0, 2, 2 cells) to (34,10, 16, 18 cells) respectively, as well as the area percentage of collagen fiber deposition and immunoexpression of eotaxin-1/10 high power fields. Additionally, the biochemical results revealed significant increases in the serum levels of TSLP, IL-4, IL-5, IL-9, IL-13, IgE and eotaxin-1 cytokines from (140, 40, 15, 38, 120, 100, 48) pg./ml to (360, 270, 130, 85, 365, 398, 110) pg./ml respectively, while analysis of ROS by flow cytometry revealed remarkable oxidative stress effects in G2 rabbits. On the other hand, treatment of rabbits with thyme oil in G4 substantially alleviated all OVA-induced alterations. Overall, our findings indicate for the first time that thyme oil can ameliorate OVA-induced BA via its immunomodulatory, anti-inflammatory, antiapoptotic, and antioxidant effects on the lung tissues of rabbits.

Stress and immunity in poultry: light management and nanotechnology as effective immune enhancers to fight stress.

The poultry industry plays a significant role in boosting the economy of several countries, particularly developing countries, and acts as a good, cheap, and affordable source of animal protein. A stress-free environment is the main target in poultry production. There are several stressors, such as cold stress, heat stress, high stocking density, and diseases that can affect birds and cause several deleterious changes. Stress reduces feed intake and growth, as well as impairs immune response and function, resulting in high disease susceptibility. These effects are correlated with higher corticosteroid levels that modulate several immune pathways such as cytokine-cytokine receptor interaction and Toll-like receptor signaling along with induction of excessive production of reactive oxygen species (ROS) and thus oxidative stress. Several approaches have been considered to boost bird immunity to overcome stress-associated effects. Of these, dietary supplementation of certain nutrients and management modifications, such as light management, are commonly considered. Dietary supplementations improve bird immunity by improving the development of lymphoid tissues and triggering beneficial immune modulators and responses. Since nano-minerals have higher bioavailability compared to inorganic or organic forms, they are highly recommended to be included in the bird's diet during stress. Additionally, light management is considered a cheap and safe approach to control stress. Changing light from continuous to intermittent and using monochromatic light instead of the normal light improve bird performance and health. Such changes in light management are associated with a reduction of ROS production and increased antioxidant production. In this review, we discuss the impact of stress on the immune system of birds and the transcriptome of oxidative stress and immune-related genes, in addition, how nano-minerals supplementations and light system modulate or mitigate stress-associated effects.

Structural properties and in vitro and in vivo immunomodulatory activity of an arabinofuranan from the fruits of Akebia quinata.

In our continuous searching for natural active polysaccharides with immunomodulatory activity, an arabinofuranan (AQP70-3) was isolated and purified from the fruits of Akebia quinata (Houtt.) Decne. by using ion-exchange chromatography and gel permeation chromatography for the first time. AQP70-3 contained both α-l-Araf and ß-l-Araf, and the absolute molecular weight was 1.06 × 104 g/mol. The backbone of AQP70-3 comprised →5)-α-l-Araf-(1→, →3,5)-α-l-Araf-(1→, and →2,5)-α-l-Araf-(1→, with branches of →1)-ß-l-Arafand →3)-α-l-Araf-(1→ residues. Biological assay suggested that AQP70-3 can stimulate phagocytic activity and promote the levels of nitric oxide (NO), interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α) of RAW264.7 cells. Furthermore, AQP70-3 was found to increase the production of reactive oxygen species (ROS) and NO in zebrafish embryo model.

Manganese-Doped Silica-Based Nanoparticles Promote the Efficacy of Antigen-Specific Immunotherapy.

Prophylactic human papillomavirus (HPV) vaccines are commercially available for prevention of infection with cancerogenic HPV genotypes but are not able to combat pre-existing HPV-associated disease. In this study, we designed a nanomaterial-based therapeutic HPV vaccine, comprising manganese (Mn4+)-doped silica nanoparticles (Mn4+-SNPs) and the viral neoantigen peptide GF001 derived from the HPV16 E7 oncoprotein. We show in mice that Mn4+-SNPs act as self-adjuvants by activating the inflammatory signaling pathway via generation of reactive oxygen species, resulting in immune cell recruitment to the immunization site and dendritic cell maturation. Mn4+-SNPs further serve as Ag carriers by facilitating endo/lysosomal escape via depletion of protons in acidic endocytic compartments and subsequent Ag delivery to the cytosol for cross-presentation. The Mn4+-SNPs+GF001 nanovaccine induced strong E7-specific CD8+ T cell responses, leading to remission of established murine HPV16 E7-expressing solid TC-1 tumors and E7-expressing transgenic skin grafts. This vaccine construct offers a simple and general strategy for therapeutic HPV and potentially other cancer vaccines.

Ceramide in apoptosis and oxidative stress in allergic inflammation and asthma.

BACKGROUND: Nothing is known about the mechanisms by which increased ceramide levels in the lung contribute to allergic responses and asthma severity. OBJECTIVE: We sought to investigate the functional role of ceramide in mouse models of allergic airway disease that recapitulate the cardinal clinical features of human allergic asthma. METHODS: Allergic airway disease was induced in mice by repeated intranasal administration of house dust mite or the fungal allergen Alternaria alternata. Processes that can be regulated by ceramide and are important for severity of allergic asthma were correlated with ceramide levels measured by mass spectrometry. RESULTS: Both allergens induced massive pulmonary apoptosis and also significantly increased reactive oxygen species in the lung. Prevention of increases in lung ceramide levels mitigated allergen-induced apoptosis, reactive oxygen species, and neutrophil infiltration. In contrast, dietary supplementation of the antioxidant α-tocopherol decreased reactive oxygen species but had no significant effects on elevation of ceramide level or apoptosis, indicating that the increases in lung ceramide levels in allergen-challenged mice are not mediated by oxidative stress. Moreover, specific ceramide species were altered in bronchoalveolar lavage fluid from patients with severe asthma compared with in bronchoalveolar lavage fluid from individuals without asthma. CONCLUSION: Our data suggest that elevation of ceramide level after allergen challenge contributes to the apoptosis, reactive oxygen species generation, and neutrophilic infiltrate that characterize the severe asthmatic phenotype. Ceramide might be the trigger of formation of Creola bodies found in the sputum of patients with severe asthma and could be a biomarker to optimize diagnosis and to monitor and improve clinical outcomes in this disease.

Walnut Polyphenol Extract Protects against Malathion- and Chlorpyrifos-Induced Immunotoxicity by Modulating TLRx-NOX-ROS.

Malathion (MT) and chlorpyrifos (CPF) are immunotoxic organophosphate pesticides that are used extensively in agriculture worldwide. Dietary polyphenols protect against a variety of toxins. In this study, walnut polyphenol extract (WPE) prevents MT- or CPF-induced toxicity to splenic lymphocytes in vitro. WPE promotes the proliferation of MT-exposed splenocytes, as indicated by increases in the proportions of splenic T-lymphocyte subpopulations (CD3+, CD4+, and CD8+ T cells) and levels of T-cell-related cytokines interleukin (IL)-2, interferon-γ, IL-4, and granzyme B, and decreases the apoptosis-associated proteins Bax and p53. WPE also significantly enhances the proliferation of CPF-exposed splenic B lymphocytes (CD19+ B cells) and levels of the B-cell-related cytokine IL-6, leading to decreases of the apoptosis-associated proteins Bax and p53. These effects are related to reduced production of reactive oxygen species (ROS), as evidenced by normalized hydroxyl radical (•OH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione (GSH) levels, which are associated with decreased expression of NADPH oxidase 2 (NOX2) and dual oxidase 1 (DUOX1). WPE inhibits the production of ROS and expression of NOX by regulating toll-like receptors 4 and 7 in MT- and CPF-exposed splenic lymphocytes. In conclusion, WPE protects against MT- or CPF-mediated immunotoxicity and inhibits oxidative damage by modulating toll-like receptor (TLR)x-NOX-ROS.

Epimedium polysaccharides attenuates hematotoxicity by reducing oxidative stress and enhancing immune function in mice model of benzene-induced bone marrow failure.

Chronic benzene (BZ) exposure is associated with multiple adverse health effects and leads to progressive bone marrow failure (BMF). BZ-induced BMF is an acquired aplastic anemia characterized by severe anemia, neutropenia and thrombocytopenia, which is likely caused by immunotoxicity and oxidative stress. Previous studies showed that Epimedium polysaccharides (EPS), a natural and major herbal compound derived from Epimedium, has immunomodulatory and antioxidant potential. The purpose of this study was to evaluate the potential efficacy of EPS against BZ-induced BMF. BMF mouse model was established by subcutaneous injection of 2 ml/kg BZ in CD1 mice. Mice received daily oral treatment with 100 mg/kg high-dose EPS and 20 mg/kg low-dose EPS for four weeks. Our data showed that EPS treatment alleviated BZ-associated weight loss and increased the number of whole blood cells in peripheral blood and nucleated cells in bone marrow. Furthermore, EPS treatment decreased apoptotic rate and reactive oxygen species production, S-phase arrest in bone marrow cells. Finally, EPS treatment improved T cell-mediated immune suppression by increasing CD3+, CD4 + T-cell counts, and CD4+/CD8+ ratio. and modulated hematopoietic cytokines including EPO, IL-11, and IL-2 in peripheral blood. Our study suggests that EPS is a potential therapeutic target to attenuate hematotoxicity induced by BZ.

Graphene Oxide-Grafted Magnetic Nanorings Mediated Magnetothermodynamic Therapy Favoring Reactive Oxygen Species-Related Immune Response for Enhanced Antitumor Efficacy.

In this study, a magnetothermodynamic (MTD) therapy is introduced as an efficient systemic cancer treatment, by combining the magnetothermal effect and the reactive oxygen species (ROS)-related immunologic effect, in order to overcome the obstacle of limited therapeutic efficacy in current magnetothermal therapy (MTT). This approach was achieved by the development of an elaborate ferrimagnetic vortex-domain iron oxide nanoring and graphene oxide (FVIOs-GO) hybrid nanoparticle as the efficient MTD agent. Such a FVIOs-GO nanoplatform was shown to have high thermal conversion efficiency, and it was further proved to generate a significantly amplified ROS level under an alternating magnetic field (AMF). Both in vitro and in vivo results revealed that amplified ROS generation was the dominant factor in provoking a strong immune response at a physiological tolerable temperature below 40 °C in a hypoxic tumor microenvironment. This was supported by the exposure of calreticulin (CRT) on 83% of the 4T1 breast cancer cell surface, direct promotion of macrophage polarization to pro-inflammatory M1 phenotypes, and further elevation of tumor-infiltrating T lymphocytes. As a result of the dual action of magnetothermal effect and ROS-related immunologic effect, impressive in vivo systemic therapeutic efficacy was attained at a low dosage of 3 mg Fe/kg with two AMF treatments, as compared to that of MTT (high dosage of 6-18 mg/kg under four to eight AMF treatments). The MTD therapy reported here has highlighted the inadequacy of conventional MTT that solely relies on the heating effect of the MNPs. Thus, by employing a ROS-mediated immunologic effect, future cancer magnetotherapies can be designed with greatly improved antitumor capabilities.

Regulation of T Cell Function by Reactive Nitrogen and Oxygen Species in Collagen-Induced Arthritis.

Aims: In this study, we investigate the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in autoimmune diseases. We focus on oxidative regulation at the interaction between antigen-presenting cells (APCs) and T cells, and consequent effect of ROS and RNS on type II collagen (CII)-induced arthritis (CIA) model in mice. Results: Mice deficient in ROS and peroxide, due to a mutation in Ncf1 gene, develop an exaggerated CIA and a stronger T cell response to CII. In contrast, nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was found to protect against CIA. The most pronounced protective effect was observed when L-NAME treatment started immediately after CII immunization. Ten days after immunization, the CII-reactive T cell-proliferative response was greater in Ncf1-mutant mice that were treated with L-NAME. T cells from L-NAME-treated mice, primed with CII, showed lower interleukin-2 secretion in response to CII in vitro. Moreover, inhibition of RNS production resulted in dysregulation of NOS1 (neuronal) expression in CII-reactive T cells. Innovation and Conclusion: The results support that deficiency of a paracrine factor as ROS and peroxide released by APC leads to pronounced activation of T cells and enhanced arthritis. An intrinsic factor might be RNS produced by NOS1, which likely enhanced T cell activation in an autocrine manner.

Early Pep-13-induced immune responses are SERK3A/B-dependent in potato.

Potato plants treated with the pathogen-associated molecular pattern Pep-13 mount salicylic acid- and jasmonic acid-dependent defense responses, leading to enhanced resistance against Phytophthora infestans, the causal agent of late blight disease. Recognition of Pep-13 is assumed to occur by binding to a yet unknown plasma membrane-localized receptor kinase. The potato genes annotated to encode the co-receptor BAK1, StSERK3A and StSERK3B, are activated in response to Pep-13 treatment. Transgenic RNAi-potato plants with reduced expression of both SERK3A and SERK3B were generated. In response to Pep-13 treatment, the formation of reactive oxygen species and MAP kinase activation, observed in wild type plants, is highly reduced in StSERK3A/B-RNAi plants, suggesting that StSERK3A/B are required for perception of Pep-13 in potato. In contrast, defense gene expression is induced by Pep-13 in both control and StSERK3A/B-depleted plants. Altered morphology of StSERK3A/B-RNAi plants correlates with major shifts in metabolism, as determined by untargeted metabolite profiling. Enhanced levels of hydroxycinnamic acid amides, typical phytoalexins of potato, in StSERK3A/B-RNAi plants are accompanied by significantly decreased levels of flavonoids and steroidal glycoalkaloids. Thus, altered metabolism in StSERK3A/B-RNAi plants correlates with the ability of StSERK3A/B-depleted plants to mount defense, despite highly decreased early immune responses.

Heracleum moellendorffii roots inhibit the production of pro-inflammatory mediators through the inhibition of NF-κB and MAPK signaling, and activation of ROS/Nrf2/HO-1 signaling in LPS-stimulated RAW264.7 cells.

BACKGROUND: Heracleum moellendorffii roots (HM-R) have been long treated for inflammatory diseases such as arthritis, backache and fever. However, an anti-inflammatory effect and the specific mechanism of HM-R were not yet clear. In this study, we for the first time explored the anti-inflammatory of HM-R. METHODS: The cytotoxicity of HM-R against RAW264.7 cells was evaluated using MTT assay. The inhibition of NO and PGE2 production by HM-R was evaluated using Griess reagent and Prostaglandin E2 ELISA Kit, respectively. The changes in mRNA or protein level following HM-R treatment were assessed by RT-PCR and Western blot analysis, respectively. RESULTS: HM-R dose-dependently blocked LPS-induced NO and PGE2 production. In addition, HM-R inhibited LPS-induced overexpression of iNOS, COX-2, IL-1ß and IL-6 in RAW264.7 cells. HM-R inhibited LPS-induced NF-κB signaling activation through blocking IκB-α degradation and p65 nuclear accumulation. Furthermore, HM-R inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. HM-R increased nuclear accumulation of Nrf2 and HO-1 expression. However, NAC reduced the increased nuclear accumulation of Nrf2 and HO-1 expression by HM-R. In HPLC analysis, falcarinol was detected from HM-R as an anti-inflammatory compound. CONCLUSIONS: These results indicate that HM-R may exert anti-inflammatory activity by inhibiting NF-κB and MAPK signaling, and activating ROS/Nrf2/HO-1 signaling. These findings suggest that HM-R has a potential as a natural material for the development of anti-inflammatory drugs.

Structure and Immunomodulatory Activity of Microparticulate Mushroom Sclerotial ß-Glucan Prepared from Polyporus rhinocerus.

In this study, an immunologically active novel microparticulate mushroom ß-glucan (PRA-1p) was prepared using an alkali-soluble glucan PRA-1 by an emulsification and cross-linking method. PRA-1 was a hyperbranched (1→3),(1→6)-ß-d-glucan with a degree of branching of 0.89, isolated from the sclerotia of Polyporus rhinocerus. PRA-1 had a rod-like conformation, while PRA-1p exhibited a monodisperse and homogeneous spherical conformation with a diameter ranging from 0.3 to 2.0 µm in water. PRA-1p significantly induced nitric oxide and reactive oxygen species production as well as morphological changes of murine macrophages (RAW 264.7 cells) and upregulated their phagocytic activity. Furthermore, PRA-1p treatment markedly enhanced the secretion of cytokines, including cutaneous T cell-attracting chemokine 27, granulocyte-colony-stimulating factor, monocyte chemoattractant protein 1, macrophage inflammatory protein 1α, macrophage inflammatory protein 2, regulated on activation, normal T cell expressed and secreted, soluble tumor necrosis factor receptor 1, and tissue inhibitors of metalloproteinases. Activation of RAW 264.7 cells triggered by PRA-1p was associated with activation of inducible nitric oxide synthase, nuclear factor κB, extracellular signal-regulated kinase, and protein kinase B. This work suggests that novel PRA-1p derived from the mushroom sclerotia of P. rhinocerus has potential application as an immunostimulatory agent.

Effect of hyperoxia on the immune status of oxygen divers and endurance athletes.

Physical activity, particularly that, exerted by endurance athletes, impacts the immune status of the human body. Prolonged duration and high-intensity endurance training lead to increased production of reactive oxygen species (ROS) and thereby to oxidative stress. Military combat swimmers (O2-divers) are regularly exposed to hyperbaric hyperoxia (HBO) in addition to intensive endurance training intervals. They are, therefore, exposed to extreme levels of oxidative stress. Several studies support that the intensity of oxidative stress essentially determines the effect on immune status. The aim of this study was to comparatively characterise peripheral blood mononuclear cells (PBMCs) of O2-divers (military combat swimmers), endurance athletes (amateur triathletes), and healthy control volunteers with respect to DNA fragmentation, immune status and signs of inflammation. Furthermore, it was investigated how PBMCs from these groups responded acutely to exposure to HBO. We showed that DNA fragmentation was comparable in PBMCs of all three groups under basal conditions directly after HBO exposure. However, significantly higher DNA fragmentation was observed in O2-divers 18 hours after HBO, possibly indicating a slower recovery. O2-divers also exhibited a proinflammatory immune status exemplified by an elevated number of CD4+CD25+ T cells, elevated expression of proinflammatory cytokine IL-12, and diminished expression of anti-inflammatory TGF-ß1 compared to controls. Supported by a decreased basal gene expression and prolonged upregulation of anti-oxidative HO-1, these data suggest that higher oxidative stress levels, as present under intermitted hyperbaric hyperoxia, e.g. through oxygen diving, promote a higher inflammatory immune status than oxidative stress through endurance training alone.

Platycodi Radix and its active compounds ameliorate against house dust mite-induced allergic airway inflammation and ER stress and ROS by enhancing anti-oxidation.

Allergic airway inflammation is an increasing global health problem, and novel strategies to prevent or ameliorate the condition are needed. The endoplasmic reticulum (ER) is involved in protein synthesis and maturation, and is a susceptible to sub-organelle stress including inflammation and ROS-amplifying signaling. Here, the effects of Platycodi Radix extracts (PRE) on house dust mite (HDM) extract (Dematophagoides pteronyssius)-induced asthma were investigated. Following 50, 100, or 200 mg/kg-PRE-treatment, the infiltration of inflammatory cells, ER stress, and NF-κB signaling were controlled. The expression of inflammatory cytokines and mucin5AC was also inhibited in the presence of PRE. Consistently, in the HDM-exposed human bronchial epithelial cells, ER stress and its associated ROS were significantly increased along with NF-κB signaling, which was also attenuated by PRE and its components. This study suggests that PRE might be useful as a therapeutic/preventive agent in HDM-associated allergic airway inflammation. ER stress and its associated ROS signaling involved in inflammation provide additional mechanistic insight into the underlying molecular mechanism.

Hyperbaric oxygen therapy: Antimicrobial mechanisms and clinical application for infections.

Hyperbaric oxygen therapy (HBOT) is a treatment procedure that involves breathing 100% O2 for a certain time and under a certain pressure. HBOT is commonly administrated as a primary or alternative therapy for different diseases such as infections. In this paper, we reviewed the general aspect of HBOT procedures, the mechanisms of antimicrobial effects and the application in the treatment of infections. Parts of the antimicrobial effects of HBOT are believed to result of reactive from the formation of reactive oxygen species (ROS). It is also said that HBOT enhances the antimicrobial effects of the immune system and has an additive or synergistic effect with certain antimicrobial agents. HBOT has been described as a useful procedure for different infections, particularly in deep and chronic infections such as necrotizing fasciitis, osteomyelitis, chronic soft tissue infections, and infective endocarditis. The anti-inflammation property of HBOT has demonstrated that it may play a significant role in decreasing tissue damage and infection expansion. Patients treated by HBOT need carful pre-examination and monitoring. If safety standards are strictly tracked, HBOT can be considered a suitable procedure with an apt rate of complication.

Impact of dibenzocyclooctadiene lignans from Schisandra chinensis on the redox status and activation of human innate immune system cells.

Redox signaling has been established as an essential component of inflammatory responses, and redox active compounds are of interest as potential immunomodulatory agents. Dibenzocyclooctadiene lignans isolated from Schisandra chinensis, a medicinal plant with widespread use in oriental medicine, have been implicated to possess immunomodulatory properties but their effects on the human innate immune system cells have not been described. In this contribution, data are presented on the impact of schisandrin, schisandrin B and schisandrin C on human monocytic cell redox status, as well as their impact on dendritic cell maturation and T cell activation capacity and cytokine production. In THP-1 cells, levels of intracellular reactive oxygen species (ROS) were elevated after 1 h exposure to schisandrin. Schisandrin B and schisandrin C decreased cellular glutathione pools, which is a phenotype previously reported to promote anti-inflammatory functions. Treatment of human primary monocytes with the lignans during their maturation to dendritic cells did not have any effect on the appearance of surface markers HLA-DR and CD86 but schisandrin B and schisandrin C suppressed the secretion of cytokines interleukin (IL)-6, IL-10 and IL-12 by the mature dendritic cells. Dendritic cells maturated in presence of schisandrin C were further cocultured with naïve CD4+ T cells, resulting in reduced IL-12 production. In THP-1 cells, schisandrin B and schisandrin C reduced the IL-6 and IL-12 production triggered by E. coli lipopolysaccharide and IL-12 production induced by an infection with Chlamydia pneumoniae. In conclusion, the studied lignans act as immunomodulatory agents by altering the cytokine secretion, but do not interfere with dendritic cell maturation. And the observed effects may be associated with the ability of the lignans to alter cellular redox status.

Garcinia Multiflora Inhibits FPR1-Mediated Neutrophil Activation and Protects Against Acute Lung Injury.

BACKGROUND/AIMS: Formyl peptide receptors (FPRs) recognize different endogenous and exogenous molecular stimuli and mediate neutrophil activation. Dysregulation of excessive neutrophil activation and the resulting immune responses can induce acute lung injury (ALI) in the host. Accordingly, one promising approach to the treatment of neutrophil-dominated inflammatory diseases involves therapeutic FPR1 inhibition. METHODS: We extracted a potent FPR1 antagonist from Garcinia multiflora Champ. (GMC). The inhibitory effects of GMC on superoxide anion release and elastase degranulation from activated human neutrophils were determined with spectrophotometric analysis. Reactive oxygen species (ROS) production and the FPR1 binding ability of neutrophils were assayed by flow cytometry. Signaling transduction mediated by GMC in response to chemoattractants was assessed with a calcium influx assay and western blotting. A lipopolysaccharide (LPS)-induced ALI mouse model was used to determine the therapeutic effects of GMC in vivo. RESULTS: GMC significantly reduced superoxide anion release, the reactive oxidants derived therefrom, and elastase degranulation mediated through selective, competitive FPR1 blocking in N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLF)-stimulated human neutrophils. In cell-free systems, GMC was unable to scavenge superoxide anions or suppress elastase activity. GMC produced a right shift in fMLF-activated concentration-response curves and was confirmed to be a competitive FPR1 antagonist. GMC binds to FPR1 not only in neutrophils, but also FPR1 in neutrophil-like THP-1 and hFPR1-transfected HEK293 cells. Furthermore, the mobilization of calcium and phosphorylation of mitogen-activated protein kinases and Akt, which are involved in FPR1-mediated downstream signaling, was competitively blocked by GMC. In an in vivo study, GMC significantly reduced pulmonary edema, neutrophil infiltration, and alveolar damage in LPS-induced ALI mice. CONCLUSION: Our findings demonstrate that GMC is a natural competitive FPR1 inhibitor, which makes it a possible anti-inflammatory treatment option for patients critically inflicted with FPR1-mediated neutrophilic lung damage.

Redox correlation in muscle lengthening and immune response in eccentric exercise.

This study was designed to examine the potential involvement of reactive oxygen species in skeletal muscle dysfunction linked with stretching in a mouse model and to explore the effects of combined antioxidant intake on peripheral leukocyte apoptosis following eccentrically-biased downhill runs in human subjects. In the mouse model, diaphragmatic muscle was stretched by 30% of its optimal length, followed by 5-min contraction. Muscle function and extracellular reactive oxygen species release was measured ex vivo. In human models, participants performed two trials of downhill running either with or without antioxidant supplementation, followed by apoptotic assay of inflammatory cells in the blood. The results showed that stretch led to decreased muscle function and prominent ROS increase during muscle contraction. In human models, we observed an elevation in circulating leukocyte apoptosis 24-48 hours following acute downhill runs. However, there is an attenuated leukocyte apoptosis following the second bout of downhill run. Interestingly, the combination of ascorbic acid (vitamin C) and α-tocopherol (vitamin E) supplementation attenuated the decrease in B-cell lymphoma 2 (Bcl-2) at 24 hours following acute downhill running. These data collectively suggest that significant ROS formation can be induced by muscle-lengthening associated with eccentric exercise, which is accompanied by compromised muscle function. The combination of antioxidants supplementation appears to have a protective role via the attenuation of decrease in anti-apoptotic protein.