Osthole attenuates airway inflammation in asthma by inhibiting the HMGB1-RAGE/TLR4-NF-κB signaling pathway.

Osthole (OS), an active component of traditional Chinese herbal medicine, has demonstrated a wide range of pharmacological effects and potential therapeutic value. This study aimed to explore the role of OS in alleviating airway inflammation in asthma. Ovalbumin (OVA) was used to induce a C57BL/6 J mouse asthma model. The mice were injected intraperitoneally with 15 mg/kg or 40 mg/kg OS. Serum IgE levels and lung inflammation were assessed; the inflammatory cell count in the BALF was determined using Wright‒Giemsa staining, and protein levels were measured by ELISA and Western blotting. Histopathological analysis of lung tissue was conducted using HE and PAS staining. OS effectively lowered IgE levels in mouse serum, reduced lung damage, and inhibited the infiltration of inflammatory cells and the proliferation of goblet cells in the lungs. Furthermore, OS reduced the number of inflammatory cells, eosinophils, and leukocytes in the BALF. With respect to cytokines, OS inhibited the levels of Th2 cytokines (IL-4, IL-5, and IL-13) and increased the levels of Th1 cytokines (IFN-γ and IL-2). Mechanistically, OS treatment inhibited activation of the HMGB1-RAGE/TLR4-NF-κB signaling pathway, thereby alleviating airway inflammation in asthma. These data suggest that OS may be a promising drug for alleviating airway inflammation in mice with bronchial asthma and provide potential molecular targets for the action of OS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-025-00812-9.