{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:09:57Z","timestamp":1785424197952,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81773857"],"award-info":[{"award-number":["81773857"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["81773857"],"award-info":[{"award-number":["81773857"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>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\u2013gene 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-dependently suppressed TNBC cell viability (IC50 = 12.12 \u03bcM) and triggered mitochondrial apoptosis, characterized by Bax upregulation, Bcl-2 downregulation, and caspase-9\/3 activation. Untargeted metabolomics identified 129 significantly altered metabolites, reflecting extensive dysregulation across lipid peroxidation, bioenergetics, and nucleotide metabolism. Topological analysis of the metabolite\u2013gene network identified the NF-\u03baB pathway as a highly interconnected hub within this perturbed landscape. Parallel experimental validation corroborated this prediction, demonstrating that Artemisian B consistently suppressed the phosphorylation of IKK\u03b1\/\u03b2, I\u03baB\u03b1, and p65, while markedly attenuating p65 nuclear translocation. Conclusions: Artemisian B induces TNBC apoptosis through extensive metabolic reprogramming coupled with concurrent inhibition of NF-\u03baB signaling. By seamlessly integrating untargeted metabolomics with network topology, our framework not only successfully bridges metabolic perturbations with signaling outcomes but also establishes a versatile, dual-perspective strategy applicable to both biochemical reaction networks and signal transduction pathways. This approach provides a robust predictive paradigm for decoding the multi-target pharmacological mechanisms of natural products.<\/jats:p>","DOI":"10.3390\/metabo16060365","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T09:57:43Z","timestamp":1779962263000},"page":"365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Untargeted Metabolomics and Metabolite\u2013Gene Network Analysis Predict NF-\u03baB Inhibition in Artemisian B-Treated Triple-Negative Breast Cancer Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Shujun","family":"Shan","sequence":"first","affiliation":[{"name":"Center of Molecular Metabolism, Nanjing University of Science and Technology, Nanjing 210094, China"},{"name":"Department of Pharmaceutical Engineering, Jiangsu Provincial Xuzhou Pharmaceutical Vocational College, Xuzhou 221116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyun","family":"Hu","sequence":"additional","affiliation":[{"name":"Center of Molecular Metabolism, Nanjing University of Science and Technology, Nanjing 210094, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guimin","family":"Xue","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Jiangsu Provincial Xuzhou Pharmaceutical Vocational College, Xuzhou 221116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Jiangsu Provincial Xuzhou Pharmaceutical Vocational College, Xuzhou 221116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixi","family":"Gan","sequence":"additional","affiliation":[{"name":"Center of Molecular Metabolism, Nanjing University of Science and Technology, Nanjing 210094, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-4969","authenticated-orcid":false,"given":"Junsong","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Molecular Metabolism, Nanjing University of Science and Technology, Nanjing 210094, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21366","DOI":"10.1038\/s41598-025-06338-6","article-title":"Robot assisted sentinel lymph node biopsy using indocyanine green combined with carbon nanoparticles staining improved detection rates in breast cancer","volume":"15","author":"Wang","year":"2025","journal-title":"Sci. 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