Flavonoids from citri reticulatae pericarpium attenuate asthma via IL-17 and NF-κB Pathways: Experimental investigation and network pharmacology

• CRPME alleviates asthma symptoms: Reduces airway inflammation, mucus hypersecretion, serum-specific IgE levels, and improves lung histopathological damage. • Multi-pathway mechanisms identified: Exerts antiasthmatic effects by regulating IL-17, HIF-1, NF-κB, and AGE-RAGE signaling pathways. • Flavonoids as key components: Hesperidin, naringin, and nobiletin are identified as the main active flavonoids with potential therapeutic effects on asthma. Citri Reticulatae Pericarpium (CRP), a classic Chinese medicinal herb rich in bioactive compounds, exhibits antioxidant, anti-inflammatory, anticancer, and cardiovascular protective activities. The ethnopharmacological properties of CRP methanol extract (CRPME) may contribute to its efficacy in asthma management. This study investigates the therapeutic effects of CRPME on ovalbumin (OVA)-induced asthma in mice and elucidates its underlying mechanisms using in vivo experiments combined with network pharmacology analysis. The major chemical constituents of CRPME were identified via high-performance liquid chromatography (HPLC). We evaluated the impact of CRPME on airway inflammation in OVA-induced asthmatic mice and employed network pharmacology to predict its antiasthmatic mechanisms, providing insights into the molecular basis of CRP's therapeutic potential in asthma. CRPME significantly alleviated OVA-induced asthmatic symptoms and lung pathological damage, while reducing interleukin (IL)-4, IL-13, and IL-17 levels in bronchoalveolar lavage fluid (BALF) and serum-specific immunoglobulin E (IgE) levels. Network pharmacology analysis revealed that CRPME may exert antiasthmatic effects by regulating IL-17, hypoxia-inducible factor 1 (HIF-1), nuclear factor-κB (NF-κB), and advanced glycation end-product receptor (AGE-RAGE) signaling pathways through active constituents including naringin, hesperidin, demethoxy hesperidin, luteolin, and nobiletin. Integrating experimental and network pharmacology data, this study demonstrates that bioactive compounds in CRPME mitigate allergic responses in asthmatic mice, supporting its potential as a therapeutic agent for allergic asthma.