Integrative network pharmacology and multi-omics reveal anisodamine hydrobromide's multi-target mechanisms in sepsis.

ABSTRACT: Sepsis, marked by hyperinflammation and subsequent immunosuppression, lacks effective phase-specific therapies. Although anisodamine hydrobromide (Ani HBr) reduced 28-day mortality in our prior trial, its mechanisms remained unclear. Here, we integrated network pharmacology, machine learning, immunological profiling, molecular simulations, and single-cell transcriptomics to elucidate Ani HBr's multi-target actions. Among 30 cross-species targets, ELANE and CCL5 emerged as core regulators via protein interaction networks, survival modeling (AUC: 0.72-0.95), and statistical significance (p < 0.05). Ani HBr inhibited ELANE-driven NET formation (HR = 1.176), associated with immunosuppression and endothelial damage, while enhancing CCL5-related cytotoxic T-cell recruitment (HR = 0.810). Docking

SUBMITTER: Chen Y 

PROVIDER: S-EPMC12313930 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature