From Traditional Decoction to Refined Formulation: Network Pharmacology Unlocks Qingdai Decoction’s Anti-Tumor Network and Enables Molecularly Compatible sTCM Design

Traditional Chinese medicine (TCM) formulations like Qingdai Decoction (QDT) offer multi-target therapeutic potential for cancer but suffer from compositional complexity and undefined mechanisms. Integrating computational and experimental approaches is critical to bridge this gap and enable rational optimization. We established an integrative network pharmacology (NP) framework to decode QDT’s anti-tumor mechanisms and design a refined formulation. LC-MS/MS identified 25 bioactive compounds targeting 520 proteins enriched in cancer pathways. Using multi-omics signatures, including transcriptomics, protein-protein interaction networks, and pan-cancer clinical prognosis, we engineered a simplified QDT (sQDT) comprising 15 compounds targeting 75 core targets. In vitro and patient-derived organoid validation demonstrated sQDT’s superior anti-tumor efficacy over traditional QDT (tQDT), with enhanced suppression of proliferation, invasion, and senescence-associated pathways. sQDT also exhibited heightened cancer specificity and minimal toxicity in normal cells. Our study pioneers a "molecular compatibility" strategy for TCM optimization, transforming complex decoctions into target-defined formulations. The NP-driven framework, uniting chemical profiling, multi-omics integration, and clinical bioinformatics, provides a blueprint for elucidating and refining multi-target therapeutics.