ovalbumin and chrysin

Although we previously identified a new hydroxymethoxyl chrysin derivative (HMOC) using ionizing radiation, the anti-inflammatory mechanism of HMOC in dendritic cells remains unclear. In this study, we investigate the effects of HMOC on phenotypic and functional changes in activated bone marrow-derived dendritic cells (BMDCs). In lipopolysaccharide (LPS)-stimulated BMDCs, HMOC treatment inhibited pro-inflammatory cytokines (TNF-α, IL-12p70, and IL-1β), surface molecules (CD80, CD86, MHC-I, and MHC-II), and antigen-presentation to MHC-I and II without a decrease in IL-10. Furthermore, HMOC increased indoleamine 2,3-dioxygenase-1 (IDO1) activity via activation of JNK and p38 signaling in the presence of LPS. Interestingly, LPS-stimulated DCs treated with HMOC inhibited the proliferation and activation of CD4

Topics: Animals; Anti-Inflammatory Agents; Antigen Presentation; Cell Survival; Cells, Cultured; Coculture Techniques; Cytokines; Dendritic Cells; Female; Flavonoids; Lipopolysaccharides; Mice, Inbred C57BL; Ovalbumin; T-Lymphocytes

This experimental study evaluated the anti-asthmatic capacity of the dihydroxyflavone chrysin in the settings of ovalbumin (OVA)-induced allergic inflammation.. The parameters that were used to assess the anti-asthmatic activity of chrysin included the specific airway resistance to histamine, the sensitivity to a chemically induced cough and the activity of chrysin on the ciliary beat frequency (CBF) of the respiratory epithelium. The anti-inflammatory potential was confirmed by the measurement of cytokine concentrations Th2 (IL-4, IL-5 and IL-13), Th1 (Granulocyte-macrophage colony-stimulating factor [GM-CSF], INF-γ and IL-12), leucocyte count in the bronchoalveolar lavage fluid (BALF) and growth factor TBF-β1 in lung homogenate.. Chronic administration of chrysin (30 mg/kg/day for 21 days) to OVA-sensitised guinea pigs showed bronchodilatory activity comparable to that of long-acting β 2 receptors agonist (LABA) salmeterol. Chrysin revealed antitussive efficiency but was not able to abolish the negative effect of OVA on CBF. Chrysin managed to ameliorate the progression of chronic airway inflammation by decreasing the count of eosinophils, lymphocytes and basophils, IL-5, L-13, GM-CSF, INF-γ in BALF, and TGF-β1 in lung homogenate.. The acquired results support the complex anti-asthmatic profile of chrysin. The flavone may represent an attractive compound for further studies concerning the prevention or treatment of asthma.

Topics: Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Antitussive Agents; Asthma; Bronchoalveolar Lavage Fluid; Cough; Cytokines; Disease Models, Animal; Disease Progression; Flavonoids; Guinea Pigs; Inflammation; Male; Ovalbumin; Salmeterol Xinafoate

Asthma, one of the significant public health problems, is triggered by certain inflammatory processes in the airways that are not addressed propitiously by current therapies. Though pieces of evidence on allergic asthma mitigation by the anti-inflammatory bioflavonoid chrysin (CHR) are accumulating, poor bioavailability, and low solubility curtail drug development. To overcome these shortcomings, CHR loaded nanoparticle (CHR-NP) was formulated, and its salutary effect in preclinical murine allergic asthma model via the peroral route was evaluated. The spherical nanosized particles showed slow, sustained release in vitro. Moreover, CHR-NP dramatically reduced the serum IgE, ovalbumin (OVA)-induced lung histological alteration, as well as Th2 (T-helper 2) cytokines in the bronchoalveolar lavage fluid (BALF). It also suppressed the elevated serum pro-inflammatory cytokines and their upstream TLR/NF-κB/NLRP3 pathway activation in lung superior to CHR and almost identical to dexamethasone (DEX). Thus this study suggests the potentiality of CHR-NP in ameliorating allergic asthma progression.

Topics: A549 Cells; Animals; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Flavonoids; Humans; Hypersensitivity; Immunoglobulin E; Inflammation Mediators; Lung; Male; Mice; Mice, Inbred BALB C; Microscopy, Atomic Force; Microscopy, Electron, Transmission; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Polylactic Acid-Polyglycolic Acid Copolymer; Toll-Like Receptors

Asthma is a chronic airway inflammatory disorder and progresses mainly due to airway remodeling. Chrysin, a natural flavonoid, has been reported to possess multiple biologic activities, including anti-inflammation, anti-oxidation and anti-proliferation. The present study aimed to investigate whether chrysin could relieve allergic airway inflammation and remodeling in a murine model of chronic asthma and the mechanism involved. The female BALB/c mice sensitized and challenged with ovalbumin (OVA) successfully developed airway hyperresponsiveness (AHR), inflammation and remodeling. The experimental data showed that chrysin could alleviate OVA-induced AHR. Chrysin could also reduce OVA-induced increases in the number of inflammatory cells, especially eosinophils, interleukin (IL) -4, and IL-13 in bronchoalveolar lavage fluid (BALF) and total IgE in serum. The decreased interferon-γ (IFN-γ) level in BALF was also upregulated by chrysin. In addition, inflammatory cell infiltration, goblet cell hyperplasia and the expression of α-smooth muscle actin (α-SMA) around bronchioles were suppressed by chrysin. Furthermore, the phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) could be decreased by chrysin, which are associated with airway smooth muscle cell (ASMC) proliferation. These results indicate the promising therapeutic effect of chrysin on chronic asthma, especially the progression of airway remodeling.

Topics: Acetylcholine; Airway Remodeling; Allergens; Animals; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Female; Flavonoids; Immunoglobulin E; Lung; Mice; Mice, Inbred BALB C; Muscle, Smooth; Ovalbumin; Proto-Oncogene Proteins c-akt

To explore the therapeutic effects of chrysin for steroid-resistant asthma in a murine model.. Lipopolysaccharide (LPS) was used to induce steroid-resistant asthma in a murine model sensitized and challenged with ovalbumin (OVA). Forty-eight female BALB/c mice were randomly divided into 6 groups of control (A), OVA (B), LPS + OVA (C), LPS + OVA + dexamethasone (D), LPS + OVA + chrysin (E) and LPS + OVA + dexamethasone + chrysin (F) (n = 8 each). At Day 1 and 14, group A received an intraperitoneal injection of phosphate buffered saline (PBS); groups B, C, D, E and F had an intraperitoneal injection of a mixture of OVA (20 µg) and aluminum hydroxide for sensitization. At Day 27, groups A and B were intranasally instilled with PBS while groups C, D, E and F had an intranasal instillation of LPS (10 µg). At Days 28, 29 and 30, groups B, C, D, E and F were challenged via airway with 1% OVA in PBS for 30 min and group A with PBS. Group D was intraperitoneally injected with dexamethasone (3 mg/kg) 30 min pre-challenge and PBS one day pre-challenge; group E received an intraperitoneal injection of chrysin (50 mg/kg) at one day and 1h pre-challenge; group F received dexamethasone (3 mg/kg) 30 min pre-challenge and chrysin (50 mg/kg) at one day and 1 h pre-challenge; groups A, B and C had PBS as above. Hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining of lung tissues were performed to observe the pathologic changes. The total cells in bronchoalveolar lavage fluid (BALF) were counted under microscope. And enzyme-linked immunosorbent assay (ELISA) was applied for detecting interleukin-4 (IL-4) and interleukin-13 (IL-13) in BALF and IgE in sera.. The inflammatory infiltration in lung tissue of group F was obviously suppressed compared with that of group C. The numbers of PAS-positive cells per bronchus divided by the total number of epithelial cells in group D, E, F were markedly lower than that in group C ((54.5 ± 6.9)%, (53.3 ± 8.2)%, (23.8 ± 7.0)% vs (71.3 ± 12.2)%, all P < 0.01). The total cells in BALF of group E and F significantly decreased versus that of group C ((1.22 ± 0.23) × 10⁴/ml, (0.98 ± 0.25) × 10⁴/ml vs (2.56 ± 0.18) × 10⁴/ml, both P < 0.01). The levels of IL-4 in group D and F were significantly less than that of group C ((118 ± 7), (124 ± 5) vs (138 ± 6) pg/ml, both P < 0.01). The levels of IL-13 in BALF of group E and F significantly decreased compared with that of group C ((787 ± 57), (484 ± 32) vs (1 121 ± 132) pg/ml, both P < 0.01). The levels of IgE in sera of group D, E, F were significantly lower those of group C ((10 310 ± 494), (10 771 ± 650), (7 529 ± 485) vs (12 618 ± 595) ng/ml, all P < 0.01).. Chrysin could improve the therapeutic efficacies of glucocorticoid for steroid-resistant asthma.

Topics: Animals; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Dexamethasone; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Flavonoids; Glucocorticoids; Injections, Intraperitoneal; Lipopolysaccharides; Lung; Mice; Mice, Inbred BALB C; Ovalbumin

Chrysin, a flavonoid obtained from various natural sources, has been reported to possess anti-inflammatory, antitumor, antioxidant and anti-allergic activities. However, its anti-inflammatory and immunoregulatory activities in asthma animal models are poorly understood. In the present study, we examined the effects of chrysin on airway inflammation and the possible mechanisms through which it acts in a murine model of allergic asthma. BALB/c mice sensitized and challenged to ovalbumin (OVA) were administered intragastrically with chrysin at a dose of 50 mg/kg daily. Chrysin significantly suppressed OVA-induced airway hyperresponsiveness (AHR) to acetylcholine chloride (Ach). Chrysin administration significantly inhibited the total inflammatory cell and eosinophil counts in bronchoalveolar lavage fluid (BALF) and total immunoglobulin E (IgE) levels in serum. Histological examination of lung tissue demonstrated that chrysin significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. In addition, chrysin triggered a switch of the immune response to allergens towards a T-helper type 1 (Th1) profile by modulating the transcription factors T-bet and GATA-3 in allergic mice. These data suggest that chrysin exhibits anti-inflammatory and immunoregulatory properties and provides new insights into the immunopharmacological role of chrysin in terms of its effects in a murine model of asthma.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Female; Flavonoids; GATA3 Transcription Factor; Immunoglobulin E; Inflammation; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; T-Box Domain Proteins; Th1 Cells; Th2 Cells

Chrysin, a flavonoid obtained from various natural sources, has been reported to act as an anti-inflammatory and antioxidant agent. However, its anti-allergic action is not fully understood.. In this study, we investigated the in vivo anti-asthmatic activity of chrysin.. The effects of chrysin were evaluated using ovalbumin (OVA) (two subcutaneous 1 mL injections of 20 μg) to induce bronchoalveolar hyperresponsiveness in rats. Chrysin, when administered at 3, 10, and 30 mg/kg, p.o., respectively, before OVA challenge, reduced inflammatory cell (total and differential cell count) infiltration into the lungs measured from bronchoalveolar lavage fluid as supported by lung histology.. The total lung injury score was reduced in a dose-dependent manner, evaluated in six different categories (infiltration of leucocytes, type of inflammatory exudates, status of bronchi, perivascular status of lung blood vessels, integrity of alveoli and activation of alveolar macrophages). Various cellular injury parameters such as alkaline phosphatase, lactate dehydrogenase, and total protein were estimated and found to be reduced by chrysin pretreatment. Further, chrysin was found to reduce nitrite concentration (NO) and lipid peroxidation, suggesting its antioxidant activity.. Chrysin showed anti-asthmatic potential, probably due to the alteration of Th1/Th2 polarization via the suppression of inducible nitric oxide synthase, nuclear factor-κB, and activation protein.

Topics: Animals; Anti-Asthmatic Agents; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cell Count; Cell Polarity; Dose-Response Relationship, Drug; Flavonoids; Lung; Organ Size; Ovalbumin; Oxidative Stress; Rats; Rats, Wistar

The flavonoids are a diverse family of chemicals commonly found in fruits and vegetables. Previously, we have shown that the two flavones, chrysin and apigenin could suppress the expression of the high affinity IgE receptor FcepsilonRI in human basophilic KU812 cells. We also demonstrated that dietary apigenin decreased IgE level in C57BL/6N mice sera.. To evaluate the anti-allergic effect of the two flavones in vivo, we evaluated the effect of the two flavones, chrysin and apigenin, on the immune system in BALB/c mice sensitized with ovalbumin (OVA).. Mice were fed experimental diets containing either of the flavones for 3 weeks and immunized with OVA. After the experimental feeding period, measurement of Igs concentration in the mice sera was performed using a sandwich ELISA. Cytokines expression in mice sera was assessed using a cytokine array. Furthermore, cytokines mRNA levels in spleen lymphocytes from mice sensitized with OVA were measured by RT-PCR.. The total IgE level in mice fed one of the two flavones were suppressed, whereas levels of IgG, IgM, and IgA were not affected. The production of interleukin (IL)-4, which is known as one of Th2 cytokines and regulates the production of IgE, was down-regulated by the chrysin or the apigenin diet. Moreover, OVA-induced mRNA expression of Th2 cytokines in spleen lymphocytes from mice sensitized with OVA, such as IL-4 and IL-13 were down-regulated by the chrysin or the apigenin diet.. The results suggest that the diet containing one of the two flavones might suppress the up-regulation of serum IgE induced by OVA-immunization through the suppression of Th2-type immune response.

Topics: Animals; Apigenin; Enzyme-Linked Immunosorbent Assay; Flavones; Flavonoids; Fruit; Immunity, Cellular; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Interleukin-4; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spleen; Th2 Cells; Vegetables