Ginkgo biloba leaf alleviates bronchial asthma via the TAS2Rs/Gβγ/SERCA signaling pathway

Bronchial asthma, a multifaceted disease involving multiple cellular components, including airway epithelial cells, mast cells, and airway smooth muscle cells (ASMC). Our previous research has highlighted the crucial role of taste type 2 receptors (TAS2Rs) in alleviating airway inflammation, allergic responses, and abnormal ASMC proliferation in bronchial asthma. Ginkgo Biloba leaf, a traditional Chinese medicine with bitter properties, has demonstrated potential therapeutic value in bronchial asthma. The current study aimed to investigate the critical role of TAS2Rs in the alleviation of bronchial asthma by G. biloba leaf. In vitro cellular experiments revealed that the aqueous decoction of G. biloba leaf (GBLAD) significantly inhibits 16HBE inflammatory responses (assessed by LDH and TNF), RBL-2H3 degranulation (including IL-3, MCP-1, calcium influx, and F-actin reorganization), and ASMC proliferation (encompassing cell cycle and migration). Intracellular calcium assays revealed that GBLAD selectively activates TAS2R4, 14, and 38 receptors. Subsequent investigation revealed that blocking the Gβγ signaling pathway, specifically targeting SERCA, resulted in a marked reduction in the ability of GBLAD to stimulate TAS2Rs and its effectiveness in alleviating asthma. UPLC-Q-Exactive MS identified bilobalide, kaempferol, and quercetin as potential bioactive compounds that activate TAS2Rs to inhibit epithelial inflammation, cell degranulation, and ASMC proliferation. Notably, the downstream mechanisms of the compounds align with the overall action of G. biloba leaf, involving SERCA in the Gβγ pathway. Our findings provide significant insights and a theoretical framework for the application of G. biloba leaf in the treatment of bronchial asthma.