ovalbumin and mangiferin

Mangiferin (MF), extracted from mango trees, is considered to have anti-inflammatory, anti-apoptotic, and antioxidant effects. However, its effects on allergic rhinitis (AR), remain unclear. We investigated the mechanisms underlying the protective action of MF in ovalbumin (OVA)-induced AR models. AR was induced by OVA challenge in BALB/c mice. Prior to this, MF and dexamethasone were administered. Mice were examined for nasal mucosal inflammation, the generation of allergen-specific cytokine response, and histopathological changes in the nasal mucosa and lung tissue. MF ameliorated nasal symptoms and nasal mucosa inflammation in OVA-induced AR and reduced inflammatory cell infiltration and epithelial disruption in these tissues. MF inhibited the overproduction of Th2/Th17 cytokines and transcription factors. MF downregulated the HO-1/Nrf2 pathways, reduced oxidative stress biomarker levels, and the NF-κB signaling pathways were inhibited. MF exerts protective effects in AR by inhibiting NF-κB and activating HO-1/Nrf2 pathways. MF could be used for the treatment of AR.

Topics: Animals; Cytokines; Heme Oxygenase-1; Inflammation; Male; Mice, Inbred BALB C; Nasal Mucosa; NF-E2-Related Factor 2; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Th17 Cells; Th2 Cells; Xanthones

Allergic rhinitis (AR) is nasal inflammation caused by allergy and the prevalence of AR is rising globally. In this investigation, we used ovalbumin-provoked AR to examine the antiallergic, anti-inflammation activities of mangiferin. Mangiferin is a xanthone found in higher plants as well as mango and it has numerous health benefits including antitumor, antioxidant, antimutagenic, antidiabetic, antibacterial, and anti-inflammatory properties. Alternatively, the antiallergic action of mangiferin on AR has been not yet investigated. Mangiferin administration reduced the symptoms of nasal allergy such as sneezing as well as rubbing in AR. Besides, the generated MDA through allergen administration was considerably diminished as a result of mangiferin treatment. Additionally, mangiferin prevented the STAT3 as well as NF-κBp65 signaling pathway activation in the cytosol, which resulted in the anti-inflammatory cytokines being upregulated, whereas, the pro-inflammatory cytokines were downregulated. Moreover, mangiferin reduced signs of ciliary loss, vascular congestion in the lamina, goblet cell elevation, and eosinophil filtration in the AR model. Hence, our findings suggest that mangiferin is a promising approach for immunotherapy in AR disease.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Interleukin-6; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Signal Transduction; STAT3 Transcription Factor; Transcription Factor RelA; Xanthones

Mangiferin is the major bioactive ingredient in the leaves of Mangifera indica L., Aqueous extract of such leaves have been traditionally used as an indigenous remedy for respiratory diseases including cough and asthma in Traditional Chinese Medicine. Mangiferin was shown to exert its anti-asthmatic effect by modulating Th1/Th2 cytokines imbalance via STAT6 signaling pathway. However, compelling evidence indicated that subtypes of T helpers and regulatory T cells other than Th1/Th2 were also involved in the pathogenesis of asthma. In current study, we investigated the effects of mangiferin on the differentiation and function of Th9, Th17 and Treg cells in a chicken egg ovalbumin (OVA)-induced asthmatic mouse model. Mangiferin significantly attenuated the symptoms of asthma attacks, reduced the total number of leukocytes, EOS and goblet cells infiltration in lung. Simultaneously, treatment with mangiferin remarkably decreased the proportion of Th9 and Th17 cells; reduced the levels of IL-9, IL-17A; inhibited the expression of PU.1 and RORγt in lung. However, the proportion of Treg cells, the expression of IL-10, TGF-β1 and Foxp3 were increased by mangiferin. Our data suggest that mangiferin exerted anti-asthmatic effect through decreasing Th9 and Th17 responses and increasing Treg response in OVA-induced asthmatic mouse model.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Egg Hypersensitivity; Female; Lung; Mangifera; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Signal Transduction; T-Lymphocytes, Regulatory; Th17 Cells; Th2 Cells; Xanthones

Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae) leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD2 in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4, IL-5 and IL-13). Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway.

Topics: Animals; Asthma; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Immunoenzyme Techniques; Mice; Mice, Inbred BALB C; Ovalbumin; Pulmonary Eosinophilia; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Th1 Cells; Th2 Cells; Xanthones

The aim was to study the effects of Mangifera indica extract and its major component mangiferin on lung inflammation response and Th2 cytokine production using a murine experimental model of allergic asthma.. BALB/c mice were intraperitoneally sensitized with 10 µg of ovoalbumin (OVA) adsorbed on aluminium hydroxide on days 0, 7 and 14. Seven days after the last injection, the mice were challenged with 2% aerosolized OVA inhalation for 30 min beginning on day 21 and continuing until day 24. To evaluate the protective effect, mice were orally treated with M. indica extract (50, 100 or 250 mg/kg) or mangiferin (50 mg/kg) from days 0 to 24. Anti-OVA immunoglobulin E, interleukin (IL)-4 and IL-5 were determined by ELISA and lungs were analysed by histology.. M. indica extract and mangiferin produced a marked reduction of airway inflammation around vessels and bronchi, inhibition of IL-4 and IL-5 cytokines in bronchoalveolar lavage fluid and lymphocyte culture supernatant, IgE levels and lymphocyte proliferation.. This is the first pre-clinical report of the anti-inflammatory properties of M. indica extract and mangiferin in experimental asthma and it could be an important part of pre-clinical requirement necessary for its use to complement the treatment of this complex disease.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin E; Inflammation; Interleukin-4; Interleukin-5; Lung; Lymphocytes; Mangifera; Mice; Mice, Inbred BALB C; Ovalbumin; Phytotherapy; Plant Bark; Plant Extracts; Plant Stems; Th2 Cells; Xanthones

The effect of mangiferin, a naturally occurring xanthone glucoside on cyclophosphamide-induced immunotoxicity and its mode of action in the immune system were investigated. To induce immunotoxicity, adult male Wistar rats were injected weekly with cyclophosphamide intraperitoneally at 100 mg/kg bodyweight. Mangiferin was injected intraperitoneally at 10 and 20 mg/kg daily for 14 days. Levamisole (3 mg/kg, i.p., daily for 14 days), a known immunostimulant that acts in immunosuppressive conditions was used as a standard drug. The effect of mangiferin on the primary immune response to ovalbumin (200 microg/rat, s.c.) was assessed at weekly intervals by measuring the serum ovalbumin-specific IgM levels. The organ weights and cellularity of spleen, thymus and bone marrow, haematology, T and B cell-dependent mitogen stimulation of splenocytes were assessed for the cellular response. Oxidative changes in lymphocytes, neutrophils and macrophages were measured at the end of the study. As well, the in vitro effect of mangiferin on cytotoxicity caused by H2O2 in primary lymphocytes was studied. The decrease in the lymphoid organ weights, cellular responses and antigen-specific IgM levels by cyclophosphamide treatment were significantly increased by repeated intraperitoneal administration of mangiferin. The enhanced lipid peroxidation and decreased catalase and superoxide dismutase activities found in lymphocytes, polymorphonuclear cells (PMN) and macrophages from cyclophosphamide treated rats were significantly ameliorated in mangiferin treated groups. The tissue injury caused by cyclophosphamide treatment was significantly suppressed by mangiferin as shown by the decrease in serum creatine phosphokinase (CPK) activity. In vitro experiments showed that pretreatment of lymphocytes with mangiferin protected from the toxicity induced by H2O2, further confirming the in vivo findings. From this study, it is evident that mangiferin exhibits an immunoprotective role mediated through the inhibition of reactive intermediate-induced oxidative stress in lymphocytes, neutrophils and macrophages.

Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Body Weight; Cell Count; Cyclophosphamide; Hydrogen Peroxide; Lymphocytes; Lymphoid Tissue; Macrophages, Peritoneal; Male; Neutrophils; Organ Size; Ovalbumin; Oxidative Stress; Rats; Rats, Wistar; Xanthones