Sophora davidii Hance leaves total alkaloids (SDLTAs) alleviate asthma through inhibiting airway inflammation and regulating TLR4/MyD88/c-Jun pathway based on systematic pharmacology and molecular docking

Abstract

Asthma is a complex heterogeneous and inflammatory disease with an increasing incidence worldwide. Here, UHPLC-Q-Exactive-MSE analysis revealed that 21 alkaloids and 1 coumarin compound (Scopoletin) were identified in SDLTAs. In mouse model, SDLTAs treatment reduced the airway pathological damage, the levels of IL-4, IL-5, IgE, MUC5AC, and splenic index. In cell model, SDLTAs treatment significantly decreased IL-6, IL-8, MUC5AC, and mucus secretion induced by LPS. Network pharmacology studies revealed that the main active ingredients of SDLTAs, including oxysophoridine, oxymatrine, scopoletin and sophoridine, target TLR4, DPP4, IL6 and TNF, as well as regulate IL-17 signaling pathway, TNF signaling pathway, and toll-like receptor signaling pathway, leading to relief of asthma on an inflammatory basis. Docking results showed that the binding energy of the main active ingredients of SDLTAs to TLR4 and MyD88 varied from −5.38 kcal/mol to −4.01 kcal/mol. Further, SDLTAs down-regulated the expression of TLR4, MyD88 and p-c-Jun.

Keywords

• Sophora davidii Hance leaves total alkaloids
• Asthma
• UHPLC-Q-Exactive-MSE analysis
• Airway epithelial injury
• Systematic pharmacology
• TLR4/MyD88/c-JUN signaling pathway