Integrated network pharmacology, molecular docking, and experimental validation reveal the therapeutic potential of ginger jujube tea against colorectal cancer
Background: Colorectal cancer (CRC) is one of the most common and lethal malignancies worldwide, with rising incidence and limited therapeutic options. Traditional Chinese medicine (TCM) formulations, known for their multi-component and multi-target synergistic actions, offer a promising alternative or adjunctive strategy. Ginger jujube tea (GJT), a classic TCM decoction, has been historically used for gastrointestinal regulation, yet its anti-CRC efficacy and pharmacological mechanisms remain unexplored. Methods: An integrated network pharmacology approach was employed to predict the active constituents of GJT and their potential CRC-related targets, followed by molecular docking to validate key compound-target interactions. The predicted pathways were further investigated through in vitro experiments using CRC cell lines (proliferation assays, reactive oxygen species (ROS) detection, apoptosis evaluation) and in vivo studies in a CRC xenograft mouse model, where tumor growth inhibition, safety profiles, and mechanistic markers (MAPK1, ESR1, HIF1A, PI3K-AKT pathway) were assessed. Results: Network pharmacology and molecular docking identified quercetin, naringenin, and other bioactive compounds as major active components, with core targets including AKT1, MAPK1, and ESR1 , predominantly enriched in the PI3K-AKT signaling pathway. In vitro , GJT dose-dependently suppressed CRC cell proliferation, significantly elevated intracellular ROS levels, and induced apoptosis. In vivo , GJT at 10 g/kg achieved a robust tumor growth inhibition rate of 64.69 ± 6.95% without observable toxicity, as confirmed by biochemical and histopathological analyses. Mechanistically, GJT downregulated MAPK1, ESR1, and HIF1A expression and inhibited PI3K-AKT pathway activation, corroborating the network-based predictions. Conclusion: GJT exerts potent anti-CRC effects through a multi-component, multi-target, and multi-pathway mechanism, consistent with the holistic philosophy of TCM. The favorable efficacy and safety profile support its potential as a complementary therapeutic candidate for CRC, warranting further clinical investigation.