Rosmarinic acid in Suhuang antitussive capsule alleviates cough variant asthma by targeting EGFR

Suhuang antitussive capsule (SH) is one of the commercially available traditional Chinese medicines (TCMs) used clinically for cough variant asthma (CVA). Over the past decade, our laboratory has systematically investigated the pharmacological properties of SH and established its potent antitussive, anti-inflammatory, expectorant, and antiasthmatic activities. In preliminary screening, rosmarinic acid (RA) detected in SH showed anti-CVA activity in vitro.

This study aimed to investigate the efficacy and mechanism of RA, as an active component of SH, for alleviating CVA.

Ovalbumin/aluminum hydroxide (OVA/Al(OH)₃) sensitization and challenge created a CVA rat model. Complementary in vitro models were generated by lipopolysaccharide (LPS) stimulation of BEAS-2B and RAW264.7 cells. Therapeutic efficacy was evaluated by cough assay, histopathology, and immune cell counts. Mechanisms were examined by Western blotting, immunofluorescence, and immunohistochemistry. Network pharmacology identified EGFR as a key target. Molecular docking, CETSA, and DARTS assays were performed to validate direct RA-EGFR engagement, and agonist rescue experiments tested EGFR-dependent efficacy.

RA markedly alleviated key CVA-associated phenotypes in vivo, supporting RA as an antitussive component of SH. Consistently, RA attenuated LPS-driven inflammatory activation in BEAS-2B and RAW264.7 cells in vitro. RA downregulated EGFR and suppressed downstream EGFR/ERK and AKT/NF-κB signaling, accompanied by reduced inflammatory responses and improved pathological changes for CVA; these effects were reversed by EGFR agonist stimulation.

This study demonstrates that RA exerts its therapeutic effect against CVA by inhibiting EGFR, thereby establishing it as a key antitussive component of SH.