Cyanidin-3-O-Glucoside: Biosynthetic Regulation, In Vivo Metabolism, and Anti-Tumor Mechanisms-An Integrated Study...

Sambucus nigra L. (European elderberry) is distinguished among medicinal and edible plants by its exceptionally high cyanidin-3-O-glucoside (C3G) content, which markedly exceeds that of common berries. This unique phytochemical profile establishes C3G as the principal bioactive constituent underlying the antitumor activity of S. nigra. While numerous reviews on elderberry have been published, none has systematically integrated C3G biosynthesis, transcriptional regulation, in vivo metabolism, and anti-tumor mechanisms specifically in S. nigra-a critical research gap that this review fills for the first time. Herein, we systematically examine the chemical structure and content distribution of C3G in S. nigra, elucidate the phenylpropanoid-flavonoid biosynthetic pathway and the regulatory patterns of the MYB-bHLH-WD40 (MBW) transcriptional complex, and highlight the current research gap regarding the cloning and functional characterization of core MBW factors in this species. We further reveal the absorption and distribution characteristics of C3G in the human body, the gut microbiota-mediated biotransformation process, and the synergistic antitumor effects of its primary metabolite, protocatechuic acid. The molecular mechanisms through which C3G exerts antitumor activity, including the induction of tumor cell apoptosis, cell cycle arrest, inhibition of epithelial-mesenchymal transition, and modulation of key signaling pathways, such as NF-κB, PI3K/AKT/mTOR, and JNK, are systematically elaborated. This is the first review to construct a comprehensive "biosynthetic regulation-in vivo metabolism-antitumor function" framework for C3G in S. nigra, thereby addressing critical research gaps and providing a theoretical foundation for the germplasm breeding of high-C3G cultivars, functional product development, and clinical adjuvant cancer therapy.