Xiebai San Alleviates Allergic Pulmonary Inflammation by Modulating Arachidonic Acid Metabolism

Background: Xiebai San (XBS), a classical Traditional Chinese Medicine formula comprising Cortex mori, Lycii Radicis Cortex, and Glycyrrhizae Radix et Rhizoma, has long been used for pulmonary inflammatory disorders. However, its underlying mechanisms remain un-clear. This study aimed to investigate the mechanisms by which XBS alleviates allergic pulmonary inflammation. Methods: Two murine models were established, consisting of a chronic ovalbumin (OVA)-induced model simulating adaptive immune responses and an acute compound 48/80-induced model triggering non-IgE-dependent mast cell activation. Pharmacodynamic indices including serum IgE, histamine, inflammatory cytokines, leukocyte profiles, and lung histopathology were evaluated. Network pharmacology was employed to predict core pathways. Arachidonic acid metabolites (AAMs) in lung tissues were quantified by targeted UPLC-MS/MS, and p38 MAPK signaling proteins were assessed by Western blot. Results: XBS significantly alleviated lung injury in both models. In the chronic OVA-induced model, XBS significantly reduced serum immunoglobulin E levels and inflammatory cell infiltration. In the acute model, XBS suppressed histamine release and mast cell-mediated inflammatory responses. Targeted metabolomics revealed differential regulatory mechanisms: XBS reduced lipoxygenase-derived metabolites, including leukotrienes and 12-hydroxyeicosatetraenoic acid in chronic inflammation, while suppressing cyclooxygenase-related prostaglandins in acute inflammation. Network pharmacology analysis identified arachidonic acid (AA) metabolism as a potential central pathway. The p38 mitogen-activated protein kinase pathway was partially involved. Conclusions: XBS effectively alleviates both chronic and acute allergic pulmonary inflammation through differential modulation of AA metabolism, providing mechanistic insights supporting its traditional use in allergic airway diseases.