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

Abstract

Background

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.

Materials

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.

Results

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.

Conclusion

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.