A Comprehensive Review of Biological Properties of Flavonoids and Their Role in the Prevention of Metabolic, Cancer and Neurodegenerative Diseases
Source abstract
Abstract
Dietary flavonoids are emerging as multifunctional bioactive compounds with significant implications for the prevention and management of chronic diseases. Integrating the latest experimental, clinical, and epidemiological evidence, this review provides a comprehensive synthesis of flavonoid classification, chemistry, dietary sources, and bioavailability, with special attention to their structural diversity and core mechanisms. Mechanistic advances related to antioxidant, anti-inflammatory, antimicrobial, anti-obesity, neuroprotective, cardioprotective, and anticancer activities are highlighted, focusing on the modulation of critical cellular pathways such as PI3K/Akt/mTOR, NF-κB, and AMPK. Evidence from in vitro and in vivo models, supported by clinical data, demonstrates flavonoids’ capacity to regulate oxidative stress, inflammation, metabolic syndrome, adipogenesis, cell proliferation, apoptosis, autophagy, and angiogenesis. An inverse correlation between flavonoid-rich dietary patterns and the risk of obesity, cancer, cardiovascular, and neurodegenerative diseases is substantiated. However, translational challenges persist, including bioavailability and the optimization of delivery strategies. In conclusion, a varied dietary intake of flavonoids constitutes a scientifically grounded approach to non-communicable disease prevention, though further research is warranted to refine clinical applications and elucidate molecular mechanisms.
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Research context
OpenAlex topics: Natural Antidiabetic Agents Studies
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Faculty of Health Sciences, University of Lomza, Akademicka 14, 18-400 Łomża, Poland
Department of Food Technology and Assessment, Institute of Food Sciences, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159 C, 02-776 Warsaw, Poland
References (100+)
Show source-provided references
1. Flavonoids: An Overview10.1017/jns.2016.41 ↗
2. Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health10.1161/CIRCRESAHA.117.309008 ↗
3. Dietary and Policy Priorities to Reduce the Global Crises of Obesity and Diabetes10.1038/s43016-019-0013-1 ↗
4. Ahn-Jarvis, J., Parihar, A., and Doseff, A. (2019). Dietary Flavonoids for Immunoregulation and Cancer: Food Design for Targeting Disease. Antioxidants, 8.10.3390/antiox8070202 ↗
5. Atrahimovich, D., Avni, D., and Khatib, S. (2021). Flavonoids-Macromolecules Interactions in Human Diseases with Focus on Alzheimer, Atherosclerosis and Cancer. Antioxidants, 10.10.3390/antiox10030423 ↗
6. Xi, X., Wang, J., Qin, Y., You, Y., Huang, W., and Zhan, J. (2022). The Biphasic Effect of Flavonoids on Oxidative Stress and Cell Proliferation in Breast Cancer Cells. Antioxidants, 11.10.3390/antiox11040622 ↗
7. Rodríguez-García, C., Sánchez-Quesada, C., and Gaforio, J.J. (2019). Dietary Flavonoids as Cancer Chemopreventive Agents: An Updated Review of Human Studies. Antioxidants, 8.10.3390/antiox8050137 ↗
8. Ullah, A., Munir, S., Badshah, S.L., Khan, N., Ghani, L., Poulson, B.G., Emwas, A.-H., and Jaremko, M. (2020). Important Flavonoids and Their Role as a Therapeutic Agent. Molecules, 25.10.3390/molecules25225243 ↗
9. Santos, E.L., Maia, B.H.L.N.S., Ferriani, A.P., and Teixeira, S.D. (2017). Flavonoids: Classification, Biosynthesis and Chemical Ecology. Flavonoids—From Biosynthesis to Human Health, InTech.10.5772/67861 ↗
10. Flavonoids as Anti-Inflammatory Agents: Implications in Cancer and Cardiovascular Disease10.1007/s00011-009-0037-3 ↗
11. Plant Polyphenols: Structure, Occurrence and Bioactivity10.1016/S1572-5995(03)80143-6 ↗
12. Dias, M.C., Pinto, D.C.G.A., and Silva, A.M.S. (2021). Plant Flavonoids: Chemical Characteristics and Biological Activity. Molecules, 26.10.3390/molecules26175377 ↗
13. Flavonoids: Antioxidant Compounds for Plant Defence… and for a Healthy Human Diet10.15835/nbha46110992 ↗
14. Zhuang, W.-B., Li, Y.-H., Shu, X.-C., Pu, Y.-T., Wang, X.-J., Wang, T., and Wang, Z. (2023). The Classification, Molecular Structure and Biological Biosynthesis of Flavonoids, and Their Roles in Biotic and Abiotic Stresses. Molecules, 28.10.3390/molecules28083599 ↗
15. Flavonoids: New Roles for Old Molecules10.1111/j.1744-7909.2010.00905.x ↗
16. do Nascimento, R.P., dos Santos, B.L., Amparo, J.A.O., Soares, J.R.P., da Silva, K.C., Santana, M.R., Almeida, Á.M.A.N., da Silva, V.D.A., Costa, M.d.F.D., and Ulrich, H. (2022). Neuroimmunomodulatory Properties of Flavonoids and Derivates: A Potential Action as Adjuvants for the Treatment of Glioblastoma. Pharmaceutics, 14.10.3390/pharmaceutics14010116 ↗
17. Flavonoids: Promising Natural Compounds against Viral Infections10.1007/s00705-017-3417-y ↗
18. Flavonoids and Type 2 Diabetes: Evidence of Efficacy in Clinical and Animal Studies and Delivery Strategies to Enhance Their Therapeutic Efficacy10.1016/j.phrs.2020.104629 ↗
19. Ginwala, R., Bhavsar, R., Chigbu, D.G.I., Jain, P., and Khan, Z.K. (2019). Potential Role of Flavonoids in Treating Chronic Inflammatory Diseases with a Special Focus on the Anti-Inflammatory Activity of Apigenin. Antioxidants, 8.10.3390/antiox8020035 ↗
20. Pharmacokinetic Properties and Drug Interactions of Apigenin, a Natural Flavone10.1080/17425255.2017.1251903 ↗
21. Bioactivity of Dietary Polyphenols: The Role of Metabolites10.1080/10408398.2018.1546669 ↗
22. The Pharmacokinetics of Flavanones10.1080/10408398.2019.1679085 ↗
23. Shah, A., and Smith, D.L. (2020). Flavonoids in Agriculture: Chemistry and Roles in Biotic and Abiotic Stress Responses, and Microbial Associations. Agronomy, 10.10.3390/agronomy10081209 ↗
24. Hydroxylation Decoration Patterns of Flavonoids in Horticultural Crops: Chemistry, Bioactivity, and Biosynthesis10.1093/hr/uhab068 ↗
25. Citrus Flavonoids and Their Antioxidant Evaluation10.1080/10408398.2020.1870035 ↗
26. Flavonoids and Metabolic Syndrome10.1111/j.1749-6632.2012.06511.x ↗
27. Roy, M., and Datta, A. (2019). Fundamentals of Phytochemicals. Cancer Genetics and Therapeutics, Springer.10.1007/978-981-13-9471-3 ↗
28. Leishmanicidal Phenolic Compounds Derived from Dalbergia cultrata10.1080/14786419.2020.1744140 ↗
29. Interaction of Isoflavonoids with Human Liver Microsomal Cytochromes P450: Inhibition of CYP Enzyme Activities10.1080/00498254.2016.1195028 ↗
30. The Relationship between Structure and in vitro Antibacterial Activity of Selected Isoflavones and Their Metabolites with Special Focus on Antistaphylococcal Effect of Demethyltexasin10.1111/lam.12361 ↗
31. Ali, A., Parisi, A., and Normanno, G. (2022). Polyphenols as Emerging Antimicrobial Agents. Emerging Modalities in Mitigation of Antimicrobial Resistance, Springer International Publishing.10.1007/978-3-030-84126-3_10 ↗
32. The Antioxidant Activity of Regularly Consumed Fruit and Vegetables Reflects Their Phenolic and Vitamin C Composition10.1080/10715760290006484 ↗
33. Martínez-Lüscher, J., Brillante, L., and Kurtural, S.K. (2019). Flavonol Profile Is a Reliable Indicator to Assess Canopy Architecture and the Exposure of Red Wine Grapes to Solar Radiation. Front. Plant Sci., 10.10.3389/fpls.2019.00010 ↗
34. Jasim, H.A., Nahar, L., Jasim, M.A., Moore, S.A., Ritchie, K.J., and Sarker, S.D. (2021). Chalcones: Synthetic Chemistry Follows Where Nature Leads. Biomolecules, 11.10.3390/biom11081203 ↗
35. Plant Flavonoids: Classification, Distribution, Biosynthesis, and Antioxidant Activity10.1016/j.foodchem.2022.132531 ↗
36. Role of Polyphenols and Carotenoids in Endothelial Dysfunction: An Overview from Classic to Innovative Biomarkers
37. Flavonoids in Our Foods: A Short Review
38. Strategy for Anthocyanins Production: From Efficient Green Extraction to Novel Microbial Biosynthesis10.1080/10408398.2022.2067117 ↗
39. Estimation of the Reducing Power and Electrochemical Behavior of Few Flavonoids and Polyhydroxybenzophenones Substantiated by Bond Dissociation Energy: A Comparative Analysis10.1007/s11030-021-10232-4 ↗
40. Classification of Fruits Based on Anthocyanin Types and Relevance to Their Health Effects10.1016/j.nut.2015.04.015 ↗
41. Gonzali, S., and Perata, P. (2020). Anthocyanins from Purple Tomatoes as Novel Antioxidants to Promote Human Health. Antioxidants, 9.10.3390/antiox9101017 ↗
42. Current Understanding of the Pathways of Flavonoid Biosynthesis in Model and Crop Plants10.1093/jxb/erx177 ↗
43. Anthocyanidins and Anthocyanins: Colored Pigments as Food, Pharmaceutical Ingredients, and the Potential Health Benefits10.1080/16546628.2017.1361779 ↗
44. Understanding the Genetic Regulation of Anthocyanin Biosynthesis in Plants—Tools for Breeding Purple Varieties of Fruits and Vegetables10.1016/j.phytochem.2018.05.013 ↗
45. The Antityrosinase and Antioxidant Activities of Flavonoids Dominated by the Number and Location of Phenolic Hydroxyl Groups10.1186/s13020-018-0206-9 ↗
46. Statistical Analysis of the Relationship Between Antioxidant Activity and the Structure of Flavonoid Compounds10.37358/RC.19.9.7497 ↗
47. Natural Antioxidants as Stabilizers for Polymers10.1016/j.polymdegradstab.2017.07.012 ↗
48. Kejík, Z., Kaplánek, R., Masařík, M., Babula, P., Matkowski, A., Filipenský, P., Veselá, K., Gburek, J., Sýkora, D., and Martásek, P. (2021). Iron Complexes of Flavonoids-Antioxidant Capacity and Beyond. Int. J. Mol. Sci., 22.10.3390/ijms22020646 ↗
49. Hydroxyflavone Metal Complexes—Molecular Structure, Antioxidant Activity and Biological Effects10.1016/j.cbi.2017.06.016 ↗
50. Xu, D., Hu, M.-J., Wang, Y.-Q., and Cui, Y.-L. (2019). Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application. Molecules, 24.10.3390/molecules24061123 ↗
51. Simunkova, M., Barbierikova, Z., Jomova, K., Hudecova, L., Lauro, P., Alwasel, S.H., Alhazza, I., Rhodes, C.J., and Valko, M. (2021). Antioxidant vs. Prooxidant Properties of the Flavonoid, Kaempferol, in the Presence of Cu(II) Ions: A ROS-Scavenging Activity, Fenton Reaction and DNA Damage Study. Int. J. Mol. Sci., 22.10.3390/ijms22041619 ↗
52. EDTA-Based Adsorbents for the Removal of Metal Ions in Wastewater10.1016/j.ccr.2021.213809 ↗
53. Mechanism of Fisetin Suppressing Superoxide Anion and Xanthine Oxidase Activity10.1016/j.jff.2019.04.044 ↗
54. Grin, P.M., Dwivedi, D.J., Chathely, K.M., Trigatti, B.L., Prat, A., Seidah, N.G., Liaw, P.C., and Fox-Robichaud, A.E. (2018). Low-Density Lipoprotein (LDL)-Dependent Uptake of Gram-Positive Lipoteichoic Acid and Gram-Negative Lipopolysaccharide Occurs through LDL Receptor. Sci. Rep., 8.10.1038/s41598-018-28777-0 ↗
55. Torello, C.O., Alvarez, M.C., and Olalla Saad, S.T. (2021). Polyphenolic Flavonoid Compound Quercetin Effects in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes. Molecules, 26.10.3390/molecules26195781 ↗
56. The Role of Nitric Oxide in Inflammation and Oxidative Stress10.15171/ipp.2019.08 ↗
57. Flavonoids Inhibit INOS Production via Mitogen Activated Proteins in Lipoteichoic Acid Stimulated Cardiomyoblasts10.1016/j.intimp.2014.04.010 ↗
58. Engwa, G.A. (2018). Free Radicals and the Role of Plant Phytochemicals as Antioxidants Against Oxidative Stress-Related Diseases. Phytochemicals—Source of Antioxidants and Role in Disease Prevention, InTech.10.5772/intechopen.76719 ↗
59. The Protective Effect of Epicatechin on Experimental Ulcerative Colitis in Mice Is Mediated by Increasing Antioxidation and by the Inhibition of NF-ΚB Pathway10.1016/j.pharep.2015.12.011 ↗
60. A Biochemical, Electrocardiographic, Electrophoretic, Histopathological and in Vitro Study on the Protective Effects of (−)Epicatechin in Isoproterenol-Induced Myocardial Infarcted Rats10.1016/j.ejphar.2011.09.036 ↗
61. Metabolism Pathways of Arachidonic Acids: Mechanisms and Potential Therapeutic Targets10.1038/s41392-020-00443-w ↗
62. The Flavonols Quercetin, Myricetin, Kaempferol, and Galangin Inhibit the Net Oxygen Consumption by Immune Complex-Stimulated Human and Rabbit Neutrophils10.5560/znc.2012-0122 ↗
63. Naringenin Inhibits Pro-inflammatory Cytokine Production in Macrophages through Inducing MT1G to Suppress the Activation of NF-κB10.1016/j.molimm.2021.07.003 ↗
64. Zhong, L., Lin, Y., Wang, C., Niu, B., Xu, Y., Zhao, G., and Zhao, J. (2022). Chemical Profile, Antimicrobial and Antioxidant Activity Assessment of the Crude Extract and Its Main Flavonoids from Tartary Buckwheat Sprouts. Molecules, 27.10.3390/molecules27020374 ↗
65. Salehi, B., Quispe, C., Chamkhi, I., El Omari, N., Balahbib, A., Sharifi-Rad, J., Bouyahya, A., Akram, M., Iqbal, M., and Docea, A.O. (2021). Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanisms and Clinical Evidence. Front. Pharmacol., 11.10.3389/fphar.2020.592654 ↗
66. Flavonoids Inhibit COX-1 and COX-2 Enzymes and Cytokine/Chemokine Production in Human Whole Blood10.1007/s10753-014-9995-x ↗
67. Al-Khayri, J.M., Sahana, G.R., Nagella, P., Joseph, B.V., Alessa, F.M., and Al-Mssallem, M.Q. (2022). Flavonoids as Potential Anti-Inflammatory Molecules: A Review. Molecules, 27.10.3390/molecules27092901 ↗
68. Sugawara, T., and Sakamoto, K. (2020). Quercetin Enhances Motility in Aged and Heat-Stressed Caenorhabditis Elegans Nematodes by Modulating Both HSF-1 Activity, and Insulin-like and P38-MAPK Signalling. PLoS ONE, 15.10.1371/journal.pone.0238528 ↗
69. Anti-Inflammatory Properties of Plant Flavonoids. Effects of Rutin, Quercetin and Hesperidin on Adjuvant Arthritis in Rat10.1016/S0014-827X(01)01111-9 ↗
70. Mitochondrial Quality Control Protects Photoreceptors against Oxidative Stress in the H2O2-Induced Models of Retinal Degeneration Diseases10.1038/s41419-021-03660-5 ↗
71. Al Aboody, M.S., and Mickymaray, S. (2020). Anti-Fungal Efficacy and Mechanisms of Flavonoids. Antibiotics, 9.10.3390/antibiotics9020045 ↗
72. Yuan, G., Guan, Y., Yi, H., Lai, S., Sun, Y., and Cao, S. (2021). Antibacterial Activity and Mechanism of Plant Flavonoids to Gram-Positive Bacteria Predicted from Their Lipophilicities. Sci. Rep., 11.10.1038/s41598-021-90035-7 ↗
73. Citrus Flavonoids: Biological Activities, Implementation in Skin Health, and Topical Applications: A Review10.1021/acsfoodscitech.2c00165 ↗
74. Zhang, H., Wang, X., He, D., Zou, D., Zhao, R., Wang, H., Li, S., Xu, Y., and Abudureheman, B. (2021). Optimization of Flavonoid Extraction from Xanthoceras Sorbifolia Bunge Flowers, and the Antioxidant and Antibacterial Capacity of the Extract. Molecules, 27.10.3390/molecules27010113 ↗
75. Antimicrobial Activity of Flavonoids10.1016/j.ijantimicag.2005.09.002 ↗
76. The Role of Sugar Signaling in Plant Defense Responses against Fungal Pathogens10.1007/s11738-014-1559-z ↗
77. Plant Extracts Rich in Polyphenols: Antibacterial Agents and Natural Preservatives for Meat and Meat Products10.1080/10408398.2020.1722060 ↗
78. Defying Multidrug Resistance! Modulation of Related Transporters by Flavonoids and Flavonolignans10.1021/acs.jafc.9b00694 ↗
79. Effects of Inhibition of RNA or Protein Synthesis on CHO Cell Cycle Progression10.1002/jcp.1041330211 ↗
80. Kaempferol, a Potential Cytostatic and Cure for Inflammatory Disorders10.1016/j.ejmech.2014.08.011 ↗
81. A Review on Oxidative Stress, Diabetic Complications, and the Roles of Honey Polyphenols10.1155/2020/8878172 ↗
82. Li, A., Zhao, Z., Zhang, S., Zhang, Z., and Shi, Y. (2021). Fungicidal Activity and Mechanism of Action of Glabridin from Glycyrrhiza glabra L.. Int. J. Mol. Sci., 22.10.3390/ijms222010966 ↗
83. Michaelis, M., Sithisarn, P., and Cinatl Jr, J. (2014). Effects of Flavonoid-Induced Oxidative Stress on Anti-H5N1 Influenza a Virus Activity Exerted by Baicalein and Biochanin A. BMC Res. Notes, 7.10.1186/1756-0500-7-384 ↗
84. Badshah, S.L., Faisal, S., Muhammad, A., Poulson, B.G., Emwas, A.H., and Jaremko, M. (2021). Antiviral Activities of Flavonoids. Biomed. Pharmacother., 140.10.1016/j.biopha.2021.111596 ↗
85. Lalani, S., and Poh, C.L. (2020). Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71). Viruses, 12.10.3390/v12020184 ↗
86. Elderberry Flavonoids Bind to and Prevent H1N1 Infection in Vitro10.1016/j.phytochem.2009.06.003 ↗
87. New Insights to Prevent Liver Fibrosis by Targeting YB-1 and Collagen Genes10.21926/obm.hg.1901014 ↗
88. Differential Antiviral and Anti-Inflammatory Mechanisms of the Flavonoids Biochanin A and Baicalein in H5N1 Influenza A Virus-Infected Cells10.1016/j.antiviral.2012.10.004 ↗
89. Khazeei Tabari, M.A., Iranpanah, A., Bahramsoltani, R., and Rahimi, R. (2021). Flavonoids as Promising Antiviral Agents against SARS-CoV-2 Infection: A Mechanistic Review. Molecules, 26.10.3390/molecules26133900 ↗
90. A Review on Anti-Cancer Properties of Quercetin in Breast Cancer10.1016/j.lfs.2020.117463 ↗
91. Estrogen Receptor Modulators Genistein, Daidzein and ERB-041 Inhibit Cell Migration, Invasion, Proliferation and Sphere Formation via Modulation of FAK and PI3K/AKT Signaling in Ovarian Cancer10.1186/s12935-018-0559-2 ↗
92. Wu, J., Zhou, T., Wang, Y., Jiang, Y., and Wang, Y. (2021). Mechanisms and Advances in Anti-Ovarian Cancer with Natural Plants Component. Molecules, 26.10.3390/molecules26195949 ↗
93. Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability10.1155/2018/8713263 ↗
94. A Mechanistic Review of the Anticancer Potential of Hesperidin, a Natural Flavonoid from Citrus Fruits10.1016/j.nutres.2021.05.011 ↗
95. Isoliquiritigenin Induces Caspase-Dependent Apoptosis via Downregulation of HPV16 E6 Expression in Cervical Cancer Ca Ski Cells10.1055/s-0033-1350956 ↗
96. Tang, S.-M., Deng, X.-T., Zhou, J., Li, Q.-P., Ge, X.-X., and Miao, L. (2020). Pharmacological Basis and New Insights of Quercetin Action in Respect to Its Anti-Cancer Effects. Biomed. Pharmacother., 121.10.1016/j.biopha.2019.109604 ↗
97. Wang, X., Yang, Y., An, Y., and Fang, G. (2019). The Mechanism of Anticancer Action and Potential Clinical Use of Kaempferol in the Treatment of Breast Cancer. Biomed. Pharmacother., 117.10.1016/j.biopha.2019.109086 ↗
98. Protective effects of Myrica rubra flavonoids against hypoxia/reoxygenation-induced cardiomyocyte injury via the regulation of the PI3K/Akt/GSK3β pathway
99. Differential Effects of Quercetin and Two of Its Derivatives, Isorhamnetin and Isorhamnetin-3-Glucuronide, in Inhibiting the Proliferation of Human Breast-Cancer MCF-7 Cells10.1021/acs.jafc.8b02420 ↗
100. Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCG) as Adjuvant in Cancer Therapy10.1016/j.clnu.2013.03.008 ↗