MHTP, a synthetic alkaloid, attenuates combined allergic rhinitis and asthma syndrome through downregulation of the p38/ERK1/2 MAPK signaling pathway in mice

•CARAS is an airway syndrome that affects a large part of the world population.•MHTP synthetic alkaloid by oral and intranasal route inhibits eosinophils.•MHTP reduces the signs of rhinitis by acting on the H1 receptor.•MHTP reduces airway tissue remodeling of CARAS.•MHTP inhibits signal transductio...

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Published in:International immunopharmacology 2021-07, Vol.96, p.107590-107590, Article 107590
Main Authors: Paiva Ferreira, Laércia K.D., Paiva Ferreira, Larissa A.M., Bezerra Barros, Grasiela C., Mozzini Monteiro, Talissa, de Araújo Silva, Luiz A., Pereira, Ramon de A., Figueiredo, Pedro T.R., Alves, Adriano Francisco, Rodrigues, Luís Cezar, Piuvezam, Marcia Regina
Format: Article
Language:English
Subjects:
Airway inflammation
Alkaloid
Alkaloids
Allergens - immunology
Allergic rhinitis
Animals
Anti-Asthmatic Agents - therapeutic use
Asthma
Asthma - drug therapy
Bronchus
Collagen
Computational fluid dynamics
Cytokines
Cytokines - metabolism
Disease Models, Animal
Drug therapy
Eosinophils
Extracellular matrix
Extracellular signal-regulated kinase
Female
Histamine
Histamine H1 receptors
Humans
Hyperactivity
Hypertrophy
Immune response
Immune system
Immunomodulation
Immunoregulation
Immunosuppressive agents
Inflammation
Interleukin 5
Kinases
Leukocyte migration
Leukocytes (eosinophilic)
Leukocytes (granulocytic)
MAP kinase
MAP Kinase Signaling System
MHTP
Mice
Mice, Inbred BALB C
Molecular Docking Simulation
Muscles
NF-κB protein
Ovalbumin
Ovalbumin - immunology
p38 Mitogen-Activated Protein Kinases - metabolism
p38/ERK1/2 MAP kinase
Receptors, Histamine H1 - metabolism
Respiratory tract diseases
Rhinitis
Rhinitis, Allergic - drug therapy
Shutdowns
Side effects
Signal transduction
Signaling
Smooth muscle
Sneezing
Tetrahydroisoquinolines - therapeutic use
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Summary:•CARAS is an airway syndrome that affects a large part of the world population.•MHTP synthetic alkaloid by oral and intranasal route inhibits eosinophils.•MHTP reduces the signs of rhinitis by acting on the H1 receptor.•MHTP reduces airway tissue remodeling of CARAS.•MHTP inhibits signal transduction of the p38/ERK1/2 MAPK pathways in granulocytes. The combined allergic rhinitis and asthma syndrome (CARAS) is a chronic airway inflammation of allergic individuals, with a type 2 immune response. Pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study was to evaluate the synthetic alkaloid, MHTP in the experimental model of CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with MHTP by intranasal or oral routes. Treated animals showed a decrease (p 
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2021.107590