The Effect of Total Alkaloid Fraction From the Roots of Lobelia clavata on Airway Inflammation in Asthmatic Mice via Network Pharmacology and Experimental Verification

ABSTRACT

Lobelia clavata has been traditionally used in Dai medicine in China for the treatment of asthma; however, its bioactive constituents and underlying mechanisms remain poorly understood. This study examined the anti‐asthmatic potential of L. clavata roots using an OVA‐induced mouse asthma model. The therapeutic effects of its three extracts—water extract (LCW), ethanolic extract (LCE), and total alkaloid fraction (LCA)—were assessed by histopathological analysis, behavioral observation, and ELISA. Among them, LCA exhibited the strongest activity, effectively ameliorating lung injury and modulating cytokine levels, specifically by decreasing LTB4, TGF‐β1, IL‐4, TNF‐α, and IL‐17, while increasing IFN‐ γ . Phytochemical investigation of LCA led to the isolation and characterization of four piperidine derivatives via chromatography, NMR, and MS. Network pharmacology analysis of these four isolated compounds identified AKT1 and mTOR as key targets, with significant enrichment in the PI3K‐AKT, Toll‐like receptor, and NF‐κB pathways. Molecular docking and western blot analysis further validated that LCA inhibited the expression of TLR4, MyD88, and total NF‐κB, as well as the phosphorylation of PI3K, AKT1, mTOR, and NF‐κB. Collectively, these findings indicate that LCA serves as the principal anti‐asthmatic active fraction of L. clavata , exerting its effects through the dual suppression of the TLR4/NF‐κB and PI3K/AKT1/mTOR signaling pathways.