Abstract

HighlightsWhat are the main findings?Artemisian B induces TNBC apoptosis through extensive metabolic reprogramming, which our topology-guided metabolite–gene network framework successfully maps to downstream signal transduction, predicting NF-κB as a central regulatory hub.This computational prediction is rigorously corroborated by parallel validation, revealing coordinated suppression of IKKα/β–IκBα–p65 phosphorylation and attenuated p65 nuclear translocation, thereby confirming the framework’s capacity to bridge metabolic perturbations with signaling outcomes.What are the implications of the main findings?Artemisian B is positioned as a multi-target modulator that concurrently disrupts TNBC metabolic homeostasis and suppresses NF-κB-driven survival programs.A superior, dual-perspective analytical strategy applicable to both biochemical reaction networks and signal transduction pathways is established, enabling researchers to decode natural product pharmacology through two complementary lenses: system-level metabolic topology and targeted signaling validation.Background:Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to the scarcity of targeted therapies and profound metabolic heterogeneity. Although Artemisian B, a dimeric sesquiterpene lactone derived from Artemisia argyi, exhibits potent antiproliferative activity, its comprehensive metabolic footprint and the translation of these perturbations into downstream signaling regulation remain poorly characterized.Methods:To address this gap, we employed an integrative analytical framework combining untargeted metabolomics, topology-guided metabolite–gene network mapping, and parallel experimental validation in MDA-MB-231 cells. This workflow systematically profiled cellular phenotypes, global metabolic reprogramming, and key signaling nodes, enabling the prioritization of high-confidence mechanistic links between metabolic alterations and signal transduction.Results:Artemisian B dose