Therapeutic Potential of Morin in Ovalbumin-induced Allergic Asthma Via Modulation of SUMF2/IL-13 and BLT2/NF-kB Signaling Pathway.
Animals
Asthma
/ drug therapy
Bronchoalveolar Lavage Fluid
/ chemistry
Flavonoids
/ pharmacology
Hemodynamics
/ drug effects
Immunoglobulin E
/ blood
Interleukin-13
/ genetics
Lung
/ metabolism
Male
NF-kappa B
/ genetics
Ovalbumin
/ immunology
Oxygen
/ metabolism
Rats
Rats, Sprague-Dawley
Receptors, Leukotriene B4
/ genetics
Signal Transduction
/ drug effects
Sulfatases
/ genetics
Superoxide Dismutase
/ metabolism
Airway hyperresponsiveness
Morin
NF-kB
Th2
cytokines
asthma
leukotriene B4 receptor 2
sulfate-modifying factor 2.
Journal
Current molecular pharmacology
ISSN: 1874-4702
Titre abrégé: Curr Mol Pharmacol
Pays: United Arab Emirates
ID NLM: 101467997
Informations de publication
Date de publication:
2019
2019
Historique:
received:
03
10
2018
revised:
30
11
2018
accepted:
17
12
2018
pubmed:
4
1
2019
medline:
17
8
2019
entrez:
4
1
2019
Statut:
ppublish
Résumé
Allergic asthma is a chronic immune-inflammatory disorder, characterized by airway inflammation and airway hyperresponsiveness (AHR). Morin is a natural flavonoid reported to exhibit inhibitory action against IgE-mediated allergic response. To determine the efficacy of murine model of ovalbumin (OVA)-induced AHR inhibition by morin and decipher the molecular mechanism involved. Sprague-Dawley rats were sensitized and challenged with OVA to induce AHR. Rats received treatment with morin (10, 30 and 100 mg/kg, p.o.) for the next 28 days. Morin (30 and 100 mg/kg) significantly and dose-dependently attenuated (p < 0.01 and p < 0.001) OVA-induced alterations in pulse oxy and lung function test, increased bronchoalveolar lavage fluid cell counts, elevated total protein and albumin levels in serum, BALF, and lungs, increased serum total and OVA-specific IgE levels and, elevated oxidative stress levels in the lung. RT-PCR analysis revealed that morin treatment (30 and 100 mg/kg) significantly (p < 0.001) up-regulated SUMF2 mRNA expression in lungs whereas mRNA expressions of BLT2, NF-κB, and Th2-cytokine (TNF-α, IL-1β, IL-4, IL-6, and IL-13) were down-regulated significantly and dose-dependently (p < 0.01 and p < 0.001). Also, histologic and ultrastructural studies showed that morin significantly inhibited (p < 0.001) OVAinduced perivascular and peribranchial inflammatory infiltration and interstitial fibrosis. Morin exhibited inhibitory effect against OVA-induced allergic asthma by activation of SUMF2 which impeded IL-13 expression and in turn attenuated Th2-cytokines, BLT2, NF-κB, and IgE levels to ameliorate AHR. Thus, our findings suggested that morin could be considered as a potential alternative therapeutic agent for the management of allergic asthma.
Sections du résumé
BACKGROUND
Allergic asthma is a chronic immune-inflammatory disorder, characterized by airway inflammation and airway hyperresponsiveness (AHR). Morin is a natural flavonoid reported to exhibit inhibitory action against IgE-mediated allergic response.
AIM
To determine the efficacy of murine model of ovalbumin (OVA)-induced AHR inhibition by morin and decipher the molecular mechanism involved.
MATERIALS AND METHODS
Sprague-Dawley rats were sensitized and challenged with OVA to induce AHR. Rats received treatment with morin (10, 30 and 100 mg/kg, p.o.) for the next 28 days.
RESULTS
Morin (30 and 100 mg/kg) significantly and dose-dependently attenuated (p < 0.01 and p < 0.001) OVA-induced alterations in pulse oxy and lung function test, increased bronchoalveolar lavage fluid cell counts, elevated total protein and albumin levels in serum, BALF, and lungs, increased serum total and OVA-specific IgE levels and, elevated oxidative stress levels in the lung. RT-PCR analysis revealed that morin treatment (30 and 100 mg/kg) significantly (p < 0.001) up-regulated SUMF2 mRNA expression in lungs whereas mRNA expressions of BLT2, NF-κB, and Th2-cytokine (TNF-α, IL-1β, IL-4, IL-6, and IL-13) were down-regulated significantly and dose-dependently (p < 0.01 and p < 0.001). Also, histologic and ultrastructural studies showed that morin significantly inhibited (p < 0.001) OVAinduced perivascular and peribranchial inflammatory infiltration and interstitial fibrosis.
CONCLUSION
Morin exhibited inhibitory effect against OVA-induced allergic asthma by activation of SUMF2 which impeded IL-13 expression and in turn attenuated Th2-cytokines, BLT2, NF-κB, and IgE levels to ameliorate AHR. Thus, our findings suggested that morin could be considered as a potential alternative therapeutic agent for the management of allergic asthma.
Identifiants
pubmed: 30605067
pii: CMP-EPUB-95541
doi: 10.2174/1874467212666190102105052
doi:
Substances chimiques
Flavonoids
0
Interleukin-13
0
NF-kappa B
0
Receptors, Leukotriene B4
0
Immunoglobulin E
37341-29-0
morin
8NFQ3F76WR
Ovalbumin
9006-59-1
Superoxide Dismutase
EC 1.15.1.1
SUMF2 protein, rat
EC 3.1.6.-
Sulfatases
EC 3.1.6.-
Oxygen
S88TT14065
Types de publication
Journal Article
Langues
eng
Pagination
122-138Informations de copyright
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