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1.
Biofactors ; 49(1): 140-152, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35861676

RESUMO

Asthma is a heterogeneous disease related to numerous inflammatory cells, among which mast cells play an important role in the early stages of asthma. Therefore, treatment of asthma targeting mast cells is of great research value. α-Asarone is an important anti-inflammatory component of the traditional Chinese medicine Acorus calamus L, which has a variety of medicinal values. To investigate whether α-asarone can alleviate asthma symptoms and its mechanism. In this study, we investigated the effect of α-asarone on mast cell activation in vivo and in vitro. The release of chemokines or cytokines, AHR (airway hyperresponsiveness), and mast cell activation were examined in a mast cell-dependent asthma model. Western blot was performed to determine the underlying pathway. α-Asarone inhibited the degranulation of LAD2 (laboratory allergic disease 2) cells and decreased IL-8, MCP-1, histamine, and TNF-α in vitro. α-Asarone reduced paw swelling and leakage of Evans blue, as well as serum histamine, CCL2, and TNF-α in vivo. In the asthma model, α-asarone showed an inhibitory effect on AHR, inflammation, mast cells activation, infiltration of inflammatory cells, and the release of IL-5 and IL-13 in lung tissue. α-Asarone decreased the levels of phosphorylated JAK2, phosphorylated ERK, and phosphorylated STAT3 induced by C48/80. Our findings suggest that α-asarone alleviates allergic asthma by inhibiting mast cell activation through the ERK/JAK2-STAT3 pathway.


Assuntos
Asma , Mastócitos , Humanos , Asma/induzido quimicamente , Asma/metabolismo , Citocinas/metabolismo , Histamina/metabolismo , Histamina/farmacologia , Janus Quinase 2/efeitos adversos , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Sistema de Sinalização das MAP Quinases
2.
J Agric Food Chem ; 69(23): 6569-6577, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34100606

RESUMO

Chrysin, one of the most pharmacologically active natural flavonoids, has been extracted from various plants. Mast cells are an important part of innate immunity-mediating anaphylaxis. Pseudo-allergic reactions are currently believed to be associated with the MAS-related GPR family member X2 (MrgX2). In this study, the anti-pseudo allergy effect of chrysin and its underlying mechanisms were studied in vitro and in vivo. Chrysin inhibited passive cutaneous anaphylaxis and systemic pseudo-allergy in vivo. LAD2 cell degranulation, calcium ion (Ca2+) influx, and adenosine 5'-triphosphate (ATP) content were significantly suppressed in a dose-dependent manner. Chrysin suppressed pseudo-allergic reactions through the PLC/IP3/Ca2+ and ERK/STAT3 serine 727 pathways downstream of MrgX2. Therefore, mitochondrial ATP, but not glycolysis, is vital for pseudo-allergic reactions mediated by MrgX2. This study provides new insights for the treatment of pseudo-allergy.


Assuntos
Anafilaxia , Receptores Acoplados a Proteínas G , Degranulação Celular , Flavonoides , Humanos , Mastócitos , Receptores Acoplados a Proteínas G/genética
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