Systems pharmacology approaches decipher the anti-cancer efficacy of ethnopharmacological agents in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) poses a significant global health burden with limited therapeutic efficacy. Chinese herbal medicines (CHMs) offer multi-target potential, yet their systematic screening and mechanistic elucidation remain challenging. We established a high-throughput multi-omics platform integrating transcriptomics, proteomics, and deep learning (autoencoder and multiple kernel learning) to screen 187 medicinal plants. Five CHMs candidates were identified and shown to modulate hub genes (e.g., AKR1B10, HMGCR, THBS1) and key pathways (TNF/IL-17/MAPK, apoptosis, ferroptosis). Proteomic validation and functional assays confirmed their roles in suppressing proliferation, migration, and inducing apoptosis in HCC cells. This study provides a robust, data-driven pipeline for natural anti-HCC drug discovery, linking specific hub genes to CHM efficacy and offering novel insights into precision ethnopharmacology.