Integrated Network Pharmacology and Cross-Species Analysis Suggest a Potential Role of AKT1/HIF1A Axis in Shuanghuanglian for Pneumonia-Myocarditis Comorbidity.

Shuanghuanglian oral liquid (SHL) is widely used in companion animals and poultry, but its molecular mechanism in pneumonia-myocarditis comorbidity and heart-lung inflammatory crosstalk remains largely unclear. This computational study investigated the conserved AKT1/HIF1A-mediated immunoregulatory mechanism of SHL and its cross-species translational potential in veterinary medicine. Network pharmacology was integrated with GO, KEGG, and Reactome enrichment analyses, protein-protein interaction network construction, ADMET evaluation, cross-species sequence homology analysis (human, dog, cattle, and pig), molecular docking, and molecular dynamics simulation. A total of 61 active compounds, 251 putative targets, and 52 common targets associated with pneumonia and myocarditis were identified. These targets were mainly enriched in inflammation- and immune-related pathways, including TNF, IL-17, AGE-RAGE, and PPAR signaling. AKT1 and HIF1A showed high sequence conservation across species (85-98%). Key compounds exhibited favorable binding affinity to AKT1, and molecular dynamics simulation suggested the stability of the Baicalein-AKT1 complex. ADMET analysis suggested favorable pharmacokinetic properties and low predicted toxicity. These findings suggest that SHL may potentially alleviate pneumonia and myocarditis through modulation of the conserved AKT1/HIF1A axis and support its potential as a complementary therapeutic approach for managing heart-lung inflammatory diseases in multiple livestock species. This entirely computational study highlights promising mechanisms that should be further validated in vivo.