Unveiling the mechanism of Pogostemon cablin (Blanco) Benth in treating heat illnesses via network pharmacology and molecular simulation.

Background: Heat illness is a dangerous condition marked by a widespread inflammatory response. Although Pogostemon cablin (Blanco) Benth and its derivatives are clinically used, their mechanisms remain unclear.

Methods: 11 heat illness patients and 14 healthy volunteers from Southwest Medical University Affiliated Hospital were enrolled. Bulk RNA sequencing of peripheral blood samples identified disease-relevant modules via weighted gene co-expression network analysis (WGCNA). Active ingredients and targets of P. cablin were retrieved from TCMSP. GO/KEGG, protein-protein interaction (PPI), and ROC analyses were performed. Core genes were localized through single-cell RNA sequencing, with compound-target interactions validated by molecular docking.

Results: Enrichment analysis revealed nine cross-targets in TNF/NF-κB pathways. Core targets (NFKBIA, PARP1) showed high diagnostic sensitivity/specificity. Single-cell data indicated predominant expression in monocytes and CD1C-CD141 dendritic cells. Molecular docking demonstrated strong affinity of quercetin/quercimeritrin for NFKBIA/PARP1/LACTB, with molecular dynamics confirming structural stability of complexes (RMSD < 2Å after 100 ns).

Conclusion: This pioneering study integrates network pharmacology and molecular simulations to elucidate P. cablin's therapeutic targets for heat illness, providing a foundation for advanced therapies.