Dual Blockade of PI3K and EGFR Pathways by Flavonoids from Idesia polycarpa Maxim Cake Meal: Valorization of Agro-Industrial Waste for NSCLC Therapy

Efficient utilization of food industry waste supports sustainable development. <i>Idesia polycarpa</i> Maxim cake meal (an oil-processing by-product) is rich in bioactive flavonoids, but the refined purification, anti-non-small cell lung cancer (NSCLC) activity, and mechanism of its total flavonoids (IPTF) remain unclear-restricting high-value use. This study optimized IPTF purification via polyamide resin gradient elution and characterized its chemical composition by HPLC/LC-MS. In vitro assays assessed IPTF's effects on A549 cell proliferation, migration, invasion, colony formation, and apoptosis; network pharmacology and molecular docking predicted mechanisms, validated via Western blotting for key signaling pathways. Results showed IPTF purity was significantly improved after purification; HPLC/LC-MS identified rutin, quercetin, and six minor components as key constituents. IPTF inhibited A549 proliferation, and network pharmacology indicated it synergistically targets the PI3K/AKT and EGFR-MAPK pathways-validated by reduced phosphorylation of p-AKT, p-EGFR, and p-ERK. This work offers a novel strategy for <i>I. polycarpa</i> cake meal valorization and highlights IPTF's potential as a multi-target natural candidate for NSCLC therapy.