ArticleProceedings of the National Academy of Sciences of the United States of America2013
Molecular basis for the action of a dietary flavonoid revealed by the comprehensive identification of apigenin human targets.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 129 citations in OpenAlex.
- Cross-Database Characterization of Flavonoids and Phenolic Acids: Integrating Drug-likeness Metrics, Molecular Interactions, and Dietary Sources.Molecules (Basel, Switzerland) · 2026Article
- Article
- Plant-Fungi Mutualism, Alternative Splicing, and Defense Responses: Balancing Symbiosis and Immunity.International journal of molecular sciences · 2025Review
- Role of Human DNA Ligases in Mediating Pharmacological Activities of Flavonoids.International journal of molecular sciences · 2025Article
- HNRNPA2B1: a novel target in pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2025Review
- Transcriptome reprogramming through alternative splicing triggered by apigenin drives cell death in triple-negative breast cancer.Cell death & disease · 2023Article
- The Antioxidative Effects of Flavones in Hypertensive Disease.Biomedicines · 2023Review
- Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice.Scientific reports · 2023Article
- An intrinsic purine metabolite AICAR blocks lung tumour growth by targeting oncoprotein mucin 1.British journal of cancer · 2023Article
- Role of Heterogeneous Nuclear Ribonucleoproteins in the Cancer-Immune Landscape.International journal of molecular sciences · 2023Review
- UPLC-MS/MS profiling, antioxidant and anti-inflammatory activities, and potential health benefits prediction of phenolic compounds in hazel leaf.Frontiers in nutrition · 2023Article
- Anti-Inflammatory Mechanisms of Dietary Flavones: Tapping into Nature to Control Chronic Inflammation in Obesity and Cancer.International journal of molecular sciences · 2022Review
- Potential Actions of Baicalein for Preventing Vascular Calcification of Smooth Muscle Cells In Vitro and In Vivo.International journal of molecular sciences · 2022Article
- IKKα Induces Epithelial-Mesenchymal Changes in Mouse Skin Carcinoma Cells That Can Be Partially Reversed by Apigenin.International journal of molecular sciences · 2022Article
- Influence of Olive Oil and Its Components on Breast Cancer: Molecular Mechanisms.Molecules (Basel, Switzerland) · 2022Review
- Multiple functions of heterogeneous nuclear ribonucleoproteins in the positive single-stranded RNA virus life cycle.Frontiers in immunology · 2022Review
- Article
- Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction.Antioxidants (Basel, Switzerland) · 2021Review
- Manipulation of Dietary Intake on Changes in Circulating Testosterone Concentrations.Nutrients · 2021Review
- Hinokiflavone and Related C-O-C-Type Biflavonoids as Anti-cancer Compounds: Properties and Mechanism of Action.Natural products and bioprospecting · 2021Review
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Flavonoids constitute the largest class of dietary phytochemicals, adding essential health value to our diet, and are emerging as key nutraceuticals. Cellular targets for dietary phytochemicals remain largely unknown, posing significant challenges for the regulation of dietary supplements and the understanding of how nutraceuticals provide health value. Here, we describe the identification of human cellular targets of apigenin, a flavonoid abundantly present in fruits and vegetables, using an innovative high-throughput approach that combines phage display with second generation sequencing. The 160 identified high-confidence candidate apigenin targets are significantly enriched in three main functional categories: GTPase activation, membrane transport, and mRNA metabolism/alternative splicing. This last category includes the heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2), a factor involved in splicing regulation, mRNA stability, and mRNA transport. Apigenin binds to the C-terminal glycine-rich domain of hnRNPA2, preventing hnRNPA2 from forming homodimers, and therefore, it perturbs the alternative splicing of several human hnRNPA2 targets. Our results provide a framework to understand how dietary phytochemicals exert their actions by binding to many functionally diverse cellular targets. In turn, some of them may modulate the activity of a large number of downstream genes, which is exemplified here by the effects of apigenin on the alternative splicing activity of hnRNPA2. Hence, in contrast to small-molecule pharmaceuticals designed for defined target specificity, dietary phytochemicals affect a large number of cellular targets with varied affinities that, combined, result in their recognized health benefits.
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