Network pharmacology-directed validation: Ginkgo biloba extract EGb761 triggers apoptosis in Colorectal Cancer by suppressing AKT /BCL2 signaling


Abstract

Background : Ginkgo biloba, a botanical that is deeply rooted in traditional Chinese medicine, has demonstrated significant anti-colorectal cancer (CRC) potential.
Method: In this study, its pharmacological mechanisms are investigated through integrated computational and experimental approaches.
Results: Through m ultiomics network pharmacology and machine learning , BCL2 was identified as the primary target, and its effects were mediated by PI3K /AKT signaling. Molecular docking and molecular dynamics simulations confirmed the stable binding between flavonoids (core components of standardized extract EGb761 ) and BCL2 . In vitrovalidation revealed that EGb761 decreased RKO cell viability (IC₅₀ = 765 μg /ml) and increased apoptosis, concomitant with decreases in p-AKT and BCL2 protein levels . Critically, these effects were reversed by the AKT activator SC79 , confirming pathway specificity.
Conclusion: Our work connects the traditional use of this extract with molecular evidence, suggesting that EGb761 is a clinically translatable AKT /BCL2 inhibitor for CRC.
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