Loquat leaves alleviate OVA-induced allergic airway inflammation by suppressing TNF-α-associated M1 macrophage...

Loquat leaves (PPY) have long been used in traditional medicine for cough, phlegm, and wheezing-related respiratory disorders. However, the anti-asthmatic mechanisms of PPY, particularly those associated with airway inflammation and macrophage-derived inflammatory injury, remain incompletely understood.

This study aimed to evaluate the protective effect of PPY against OVA-induced allergic asthma and to clarify whether its action involves TNF-α-mediated M1 macrophage polarization and MMP12 expression.

An OVA-induced allergic asthmatic mouse model was used to assess AHR, pathological injury, inflammatory cell infiltration, cytokine/chemokine profiles, and airway inflammatory mediators. Network pharmacology, transcriptomic analysis, GEO dataset mining, WGCNA, molecular docking, and molecular dynamics simulation were integrated to identify candidate pathways, targets, and active components, with a focus on TNF-α/TNF-R1, CD86, MMP12, and quercetin. A Diprovocim rescue assay was used to examine whether enhanced TNF-α-associated inflammatory activation could attenuate the effects of PPY. PPY-containing serum was used for in vitro pharmacodynamic validation, and quercetin was evaluated as a candidate active component in LPS-induced BEAS-2B and RAW264.7 cells.

PPY reduced AHR, cough and asthma-like responses, lung inflammatory infiltration, collagen deposition, BALF inflammatory cells, and OVA-induced cytokine/chemokine imbalance. Transcriptomic and network analyses highlighted TNF, IL-17, NF-κB, and MMP12-related inflammatory pathways. Molecular docking and molecular dynamics simulations predicted potential interactions among quercetin, TNF-α/TNF-R1, MMP12, and CD86. PPY suppressed TNF-α/TNF-R1/TRAF2 signaling, NF-κB activation, NLRP3 inflammasome activation, M1 macrophage polarization, and MMP12 expression. Diprovocim attenuated the PPY-mediated suppression of allergic airway inflammation, M1 macrophage polarization, and MMP12 expression in asthmatic mice. PPY-containing serum and quercetin each attenuated LPS-induced anti-inflammatory effects in BEAS-2B and RAW264.7 cells.

PPY attenuates OVA-induced allergic airway inflammation in association with inhibition of TNF-α-mediated M1 macrophage polarization and MMP12 expression, with quercetin serving as a candidate PPY-related active component. These findings provide experimental support for the traditional use of PPY in asthma-related inflammatory respiratory disorders.