Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice
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 N...
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| Language: | English |
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Associação Brasileira de Divulgação Científica
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017000800612&lng=en&tlng=en |
| _version_ | 1819157677573406720 |
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| author | L.-L. Liu F.-H. Li Y. Zhang X.-F. Zhang J. Yang |
| author_facet | L.-L. Liu F.-H. Li Y. Zhang X.-F. Zhang J. Yang |
| author_sort | L.-L. Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T16:12:34Z |
| format | Article |
| id | doaj.art-a458e250cac44991b347ba48a3fce5b8 |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-12-22T16:12:34Z |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-a458e250cac44991b347ba48a3fce5b82022-12-21T18:20:27ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X50810.1590/1414-431x20175991S0100-879X2017000800612Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic miceL.-L. LiuF.-H. LiY. ZhangX.-F. ZhangJ. YangAsthma 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017000800612&lng=en&tlng=enAsthmaInflammationNotch signalingPI3KTangeretinT-helper cells |
| spellingShingle | L.-L. Liu F.-H. Li Y. Zhang X.-F. Zhang J. Yang Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice Brazilian Journal of Medical and Biological Research Asthma Inflammation Notch signaling PI3K Tangeretin T-helper cells |
| title | Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice |
| title_full | Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice |
| title_fullStr | Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice |
| title_full_unstemmed | Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice |
| title_short | Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice |
| title_sort | tangeretin has anti asthmatic effects via regulating pi3k and notch signaling and modulating th1 th2 th17 cytokine balance in neonatal asthmatic mice |
| topic | Asthma Inflammation Notch signaling PI3K Tangeretin T-helper cells |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017000800612&lng=en&tlng=en |
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