Tanshinone IIA attenuates airway inflammation and airway remodeling in bronchial asthma by inhibiting p38/NF-κB and AKT/HIF-1α

Airway inflammation and airway remodeling are central pathological features of bronchial asthma, yet the therapeutic potential and underlying mechanism of Tanshinone IIA (Tan IIA) in this context remain poorly understood. In this study, we used a chronic bronchial asthma mouse model together with in vitro human bronchial epithelial cells (16HBEs) and human tracheal smooth muscle cells (HTSMCs). The results demonstrated that Tan IIA reduced Th2 cytokines (IL-4, IL-5, and IL-13), tissue remodeling factors (VEGF and TGF-β1), and eosinophils, neutrophils, and lymphocytes counts in bronchoalveolar lavage fluid (BALF). Histological analysis demonstrated that Tan IIA alleviated airway inflammatory cell infiltration, epithelial damage, basement membrane thickening, goblet cell hyperplasia, mucus secretion, and subepithelial Collagen deposition. Mechanistically, Tan IIA decreased phosphorylated p38 (p-p38) and Akt (p-AKT), and inhibited nuclear translocation of NF-κB and HIF-1α in vivo. These in vivo findings were corroborated by in vitro experiments. In 16HBEs, Tan IIA suppressed p-p38 activation and NF-κB nuclear translocation, whereas in HTSMCs, it decreased p-AKT levels and inhibited HIF-1α nuclear translocation. Collectively, these findings indicate that Tan IIA attenuates airway inflammation and remodeling by inhibiting the p38/NF-κB and Akt/HIF-1α signaling pathways, highlighting Tan IIA as a promising therapeutic candidate for bronchial asthma.

AKT/HIF-1α; Asthma; Tan IIA; airway inflammation; airway remodeling; p38/NF-κB.