Systemic Pharmacology & Molecular Docking: Probe Quince Seeds' Cough Suppressant Mechanism

Quince seeds (WBZ) are a traditional herbal remedy for cough, but their pharmacological mechanisms remain incompletely understood. This study aims to clarify the antitussive mechanism of WBZ using a systems pharmacology approach.

Active compounds in WBZ were screened according to ADME criteria. Direct targets were predicted using a Weighted Ensemble Similarity (WES) model. Pathway enrichment analyses (GO and KEGG) were performed on the predicted targets. This was integrated with differential gene expression analysis from an asthma/COPD dataset (GSE148004). Key compound-target interactions were validated via molecular docking.

We identified 25 active compounds targeting 143 human proteins. Enrichment analysis highlighted key pathways, including serotonergic synapse, calcium signaling, and inflammatory mediator regulation of TRP channels. Molecular docking confirmed strong binding of core compounds (e.g., quercetin, oleanolic acid) to central targets such as HTR1A, HTR2A, and PRKCB.

Mechanistically, WBZ appears to exert antitussive effects through a dual Central-peripheral Mechanism. Centrally, components like quercetin may target presynaptic HTR1A to modulate the cough reflex. Peripherally, inhibition of HTR2A and PRKCB could alleviate bronchoconstriction, while ADCY5 modulation may reduce TRP channel sensitization via cAMP signaling. This multi-target synergy provides a plausible explanation for WBZ's traditional use in cough relief.

This study comprehensively delineates the systemic mechanism of WBZ against cough, offering a theoretical foundation for its clinical application and further development. The integrative strategy combining systems pharmacology with molecular docking presents a useful paradigm for researching complex herbal medicines.