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The effects of proresolution of ellagic acid in an experimental model of allergic airway inflammation.

Alves Cde F, Angeli GN, Favarin DC, de Andrade EL, Chica JE, Faccioli LH, da Silva PR, Rogerio Ade P - Mediators Inflamm. (2013)

Bottom Line: Dexamethasone (1 mg/kg; subcutaneous route) was used as a positive control.Ellagic acid accelerated the resolution of airways inflammation by decreasing total leukocytes and eosinophils numbers in the bronchoalveolar lavage fluid (BALF), the mucus production and lung inflammation in part by reducing IL-5 concentration, eosinophil peroxidase (EPO) activity, and P-selectin expression, but not activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) pathways.In addition, ellagic acid enhanced alveolar macrophage phagocytosis of IgG-OVA-coated beads ex vivo, a new proresolving mechanism for the clearance of allergen from the airways.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de ImunoFarmacologia Experimental (LIFE), Departamento de Clínica Médica, Instituto de Ciências da Saúde, Universidade Federal do Triângulo Mineiro (UFTM), Rua Manoel Carlos 162, 38025-380 Uberaba, MG, Brazil.

ABSTRACT
Asthma is a disease of airway inflammation characterized by airway hyperresponsiveness, eosinophilic inflammation, and hypersecretion of mucus. Ellagic acid, a compound derived from medicinal plants and fruits, has shown anti-inflammatory activity in several experimental disease models. We used the classical experimental model, in BALB/c mice, of sensibilization with ovalbumin to determine the effect of ellagic acid (10 mg/kg; oral route) in the resolution of allergic airways response. Dexamethasone (1 mg/kg; subcutaneous route) was used as a positive control. The control group consisted of nonimmunized mice that received challenge with ovalbumin. Ellagic acid and dexamethasone or vehicle (water) were administered before or after intranasal allergen challenge. Ellagic acid accelerated the resolution of airways inflammation by decreasing total leukocytes and eosinophils numbers in the bronchoalveolar lavage fluid (BALF), the mucus production and lung inflammation in part by reducing IL-5 concentration, eosinophil peroxidase (EPO) activity, and P-selectin expression, but not activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) pathways. In addition, ellagic acid enhanced alveolar macrophage phagocytosis of IgG-OVA-coated beads ex vivo, a new proresolving mechanism for the clearance of allergen from the airways. Together, these findings identify ellagic acid as a potential therapeutic agent for accelerating the resolution of allergic airways inflammation.

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Related in: MedlinePlus

Ellagic acid demonstrates therapeutic anti-inflammatory activity on the resolution phase in the experimental airways allergic inflammation model. Mice received ellagic acid (10 mg/kg, p.o.), dexamethasone (1 mg/kg, s.c.), or vehicle (water, p.o.) after ovalbumin challenge at 18, 19, and 20 days (see Section 2) and were euthanized on 21 or 25 days and cells in bronchoalveolar lavage were counted (a). BALF cells and leukocytes subset at 21 days (b); BALF cells and leukocytes subset at 25 days (c). One group of animals received vehicle (p.o.) only (control group). EPO concentration in the lung at 21 day (d). The resolution interval (Ri) (e). Results represent the mean ± SEM, of two or more independent experiments with four mice per group per experiment. *P < 0.05 compared with control group; #P < 0.05 compared with ovalbumin + vehicle group.
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fig2: Ellagic acid demonstrates therapeutic anti-inflammatory activity on the resolution phase in the experimental airways allergic inflammation model. Mice received ellagic acid (10 mg/kg, p.o.), dexamethasone (1 mg/kg, s.c.), or vehicle (water, p.o.) after ovalbumin challenge at 18, 19, and 20 days (see Section 2) and were euthanized on 21 or 25 days and cells in bronchoalveolar lavage were counted (a). BALF cells and leukocytes subset at 21 days (b); BALF cells and leukocytes subset at 25 days (c). One group of animals received vehicle (p.o.) only (control group). EPO concentration in the lung at 21 day (d). The resolution interval (Ri) (e). Results represent the mean ± SEM, of two or more independent experiments with four mice per group per experiment. *P < 0.05 compared with control group; #P < 0.05 compared with ovalbumin + vehicle group.

Mentions: In the view of ellagic acid's protective actions in the airways, we next evaluated the influence of ellagic acid on the resolution of established airway inflammation. After animals were ovalbumin-sensitized and intranasal-challenged, ellagic acid, dexamethasone, or vehicle was administered for 3 consecutive days (protocol days 18–20), and no further allergen challenges were performed (Figure 2(a)). BALF leukocytes were enumerated on days 21 and 25. In both days, the numbers of BALF total cells, eosinophils, macrophages, and lymphocytes from the vehicle-treated group were significantly increased compared to the control group (Figures 2(b) and 2(c)). Ellagic acid or dexamethasone decreased the BALF eosinophil numbers at day 21 about 70% from 1.31 ± 0.11 (vehicle) to 0.39 ± 0.07 (ellagic acid) or 0.82 ± 0.07 (~37%) (dexamethasone) (mean × 106/mL ± SEM). No significant difference was observed in the neutrophils, lymphocytes, and macrophages number of animals treated with ellagic acid or dexamethasone compared to vehicle-treated group (Figure 2(b)). At day 25, ellagic acid and dexamethasone treatment decreased eosinophil numbers in the BALF (Figure 2(c)). In this point, BALF eosinophils were decreased by ∼80% from 1.10 ± 0.12 (vehicle) to 0.23 ± 0.05 (ellagic acid) or 0.38 ± 0.05 (~65%) (dexamethasone). Ellagic acid, different from dexamethasone, increased the number of lymphocytes from 0.10 ± 0.02 (vehicle) to 0.32 ± 0.03 (ellagic acid) (Figure 2(c)). No significant difference was observed in the neutrophils and macrophages number of animals treated with ellagic acid or dexamethasone compared to vehicle-treated group.


The effects of proresolution of ellagic acid in an experimental model of allergic airway inflammation.

Alves Cde F, Angeli GN, Favarin DC, de Andrade EL, Chica JE, Faccioli LH, da Silva PR, Rogerio Ade P - Mediators Inflamm. (2013)

Ellagic acid demonstrates therapeutic anti-inflammatory activity on the resolution phase in the experimental airways allergic inflammation model. Mice received ellagic acid (10 mg/kg, p.o.), dexamethasone (1 mg/kg, s.c.), or vehicle (water, p.o.) after ovalbumin challenge at 18, 19, and 20 days (see Section 2) and were euthanized on 21 or 25 days and cells in bronchoalveolar lavage were counted (a). BALF cells and leukocytes subset at 21 days (b); BALF cells and leukocytes subset at 25 days (c). One group of animals received vehicle (p.o.) only (control group). EPO concentration in the lung at 21 day (d). The resolution interval (Ri) (e). Results represent the mean ± SEM, of two or more independent experiments with four mice per group per experiment. *P < 0.05 compared with control group; #P < 0.05 compared with ovalbumin + vehicle group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3860142&req=5

fig2: Ellagic acid demonstrates therapeutic anti-inflammatory activity on the resolution phase in the experimental airways allergic inflammation model. Mice received ellagic acid (10 mg/kg, p.o.), dexamethasone (1 mg/kg, s.c.), or vehicle (water, p.o.) after ovalbumin challenge at 18, 19, and 20 days (see Section 2) and were euthanized on 21 or 25 days and cells in bronchoalveolar lavage were counted (a). BALF cells and leukocytes subset at 21 days (b); BALF cells and leukocytes subset at 25 days (c). One group of animals received vehicle (p.o.) only (control group). EPO concentration in the lung at 21 day (d). The resolution interval (Ri) (e). Results represent the mean ± SEM, of two or more independent experiments with four mice per group per experiment. *P < 0.05 compared with control group; #P < 0.05 compared with ovalbumin + vehicle group.
Mentions: In the view of ellagic acid's protective actions in the airways, we next evaluated the influence of ellagic acid on the resolution of established airway inflammation. After animals were ovalbumin-sensitized and intranasal-challenged, ellagic acid, dexamethasone, or vehicle was administered for 3 consecutive days (protocol days 18–20), and no further allergen challenges were performed (Figure 2(a)). BALF leukocytes were enumerated on days 21 and 25. In both days, the numbers of BALF total cells, eosinophils, macrophages, and lymphocytes from the vehicle-treated group were significantly increased compared to the control group (Figures 2(b) and 2(c)). Ellagic acid or dexamethasone decreased the BALF eosinophil numbers at day 21 about 70% from 1.31 ± 0.11 (vehicle) to 0.39 ± 0.07 (ellagic acid) or 0.82 ± 0.07 (~37%) (dexamethasone) (mean × 106/mL ± SEM). No significant difference was observed in the neutrophils, lymphocytes, and macrophages number of animals treated with ellagic acid or dexamethasone compared to vehicle-treated group (Figure 2(b)). At day 25, ellagic acid and dexamethasone treatment decreased eosinophil numbers in the BALF (Figure 2(c)). In this point, BALF eosinophils were decreased by ∼80% from 1.10 ± 0.12 (vehicle) to 0.23 ± 0.05 (ellagic acid) or 0.38 ± 0.05 (~65%) (dexamethasone). Ellagic acid, different from dexamethasone, increased the number of lymphocytes from 0.10 ± 0.02 (vehicle) to 0.32 ± 0.03 (ellagic acid) (Figure 2(c)). No significant difference was observed in the neutrophils and macrophages number of animals treated with ellagic acid or dexamethasone compared to vehicle-treated group.

Bottom Line: Dexamethasone (1 mg/kg; subcutaneous route) was used as a positive control.Ellagic acid accelerated the resolution of airways inflammation by decreasing total leukocytes and eosinophils numbers in the bronchoalveolar lavage fluid (BALF), the mucus production and lung inflammation in part by reducing IL-5 concentration, eosinophil peroxidase (EPO) activity, and P-selectin expression, but not activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) pathways.In addition, ellagic acid enhanced alveolar macrophage phagocytosis of IgG-OVA-coated beads ex vivo, a new proresolving mechanism for the clearance of allergen from the airways.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de ImunoFarmacologia Experimental (LIFE), Departamento de Clínica Médica, Instituto de Ciências da Saúde, Universidade Federal do Triângulo Mineiro (UFTM), Rua Manoel Carlos 162, 38025-380 Uberaba, MG, Brazil.

ABSTRACT
Asthma is a disease of airway inflammation characterized by airway hyperresponsiveness, eosinophilic inflammation, and hypersecretion of mucus. Ellagic acid, a compound derived from medicinal plants and fruits, has shown anti-inflammatory activity in several experimental disease models. We used the classical experimental model, in BALB/c mice, of sensibilization with ovalbumin to determine the effect of ellagic acid (10 mg/kg; oral route) in the resolution of allergic airways response. Dexamethasone (1 mg/kg; subcutaneous route) was used as a positive control. The control group consisted of nonimmunized mice that received challenge with ovalbumin. Ellagic acid and dexamethasone or vehicle (water) were administered before or after intranasal allergen challenge. Ellagic acid accelerated the resolution of airways inflammation by decreasing total leukocytes and eosinophils numbers in the bronchoalveolar lavage fluid (BALF), the mucus production and lung inflammation in part by reducing IL-5 concentration, eosinophil peroxidase (EPO) activity, and P-selectin expression, but not activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) pathways. In addition, ellagic acid enhanced alveolar macrophage phagocytosis of IgG-OVA-coated beads ex vivo, a new proresolving mechanism for the clearance of allergen from the airways. Together, these findings identify ellagic acid as a potential therapeutic agent for accelerating the resolution of allergic airways inflammation.

Show MeSH
Related in: MedlinePlus