Flavonoids as Redox-modulating Therapeutics: Structure–activity Relationships and Nanocarrier Strategies in Medicinal Chemistry

Abstract:

Flavonoids are a class of phenolic compounds that display significant antioxidant, antiinflammatory, and cytoprotective activities. Despite their considerable pharmacological activities, flavonoids and their derivatives face significant barriers in their clinical application due to their poor aqueous solubility, rapid first-pass metabolism, and limited inability to traverse biological barriers. Recent progress in the field of nanotechnology has stimulated the design and application of multi-functional nano-carriers for flavonoids, which are tailored to overcome these barriers and maximize flavonoid bioavailability. This review attempts to compile existing knowledge regarding the relationship between flavonoids, bioactivity, and oxidative stress, as well as their bioavailability and the application of modern nanotechnologies. The molecular mechanisms, barriers, and novel nanotechnologies are discussed in detail, including their rationale, parameters, and efficacy in flavonoids’ delivery. The application of artificial intelligence in formulation, multi-omics, and in vitro models is also discussed in the context of a novel approach to flavonoids’ application and their potential in the treatment and prevention of oxidative stress, neurodegenerative, and inflammatory diseases. This comprehensive review is expected to serve as a significant reference source for those seeking to develop and apply nanotechnology in phytochemical medicine.