Molecular Mechanisms of Anticancer Activity in Codonopsis pilosula Bioactive Compounds and Their Therapeutic Targets

Abstract: The present study elucidates the molecular mechanisms underlying the anticancer effects of Codonopsis pilosula bioactive compounds. Polysaccharides exert immunomodulatory effects by activating macrophages and NK cells through TLR4/NF-κB signaling, while inhibiting angiogenesis via VEGF/VEGFR2 and TGF-β/Smad pathway suppression. Saponins like lobetyolin disrupt glutamine metabolism by downregulating ASCT2 expression through c-Myc inhibition, inducing mitochondrial apoptosis via ROS/JNK activation. Polyacetylenes, particularly codonolactone, suppress EMT by blocking TGF-β-induced Smad2/3 phosphorylation and Runx2 nuclear translocation. Phenolic compounds such as luteolin induce G2/M arrest through CDK1/cyclin B1 modulation and inhibit migration via PI3K/AKT/ESR1 axis regulation. The study provides a comprehensive molecular basis for C. pilosula's anticancer potential, supporting its development as a multi-targeted therapeutic agent. Future research should focus on clinical translation of these mechanistically defined bioactive compounds.