Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice
Braz. j. med. biol. res; 50 (8), 2017
Publication year: 2017
Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.
Animales Recién Nacidos, Antiasmáticos/uso terapéutico, Asma/tratamiento farmacológico, Asma/inmunología, Citocinas/efectos de los fármacos, Citocinas/inmunología, Modelos Animales de Enfermedad, Flavonas/uso terapéutico, Ratones Endogámicos BALB C, Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos, Proteínas Proto-Oncogénicas c-akt/inmunología, Transducción de Señal/efectos de los fármacos, Células TH1/efectos de los fármacos, Células TH1/inmunología, Células Th17/efectos de los fármacos, Células Th17/inmunología, Células Th2/efectos de los fármacos, Células Th2/inmunología