Chrysin: Phytochemistry, Pharmacology, Pharmacokinetics, Nano-Delivery Strategy, and Derivative Innovation

Chrysin, a naturally occurring flavonoid and FDA-approved dietary supplement, is ubiquitously present in fruits, vegetables, and mushrooms. Emerging evidence highlights its broad-spectrum therapeutic potential against diverse pathologies, including inflammation, cancers, organ injuries, metabolic dysfunctions, and neuropathic pain. Nevertheless, critical gaps persist in understanding its physicochemical properties, pharmacokinetic profile, and precise molecular mechanisms, and there remains only limited systematic evaluation of advanced drug delivery systems and structural modification strategies. This review comprehensively synthesizes cutting-edge advances in understanding chrysin's natural sources, physicochemical characteristics, pharmacological activities, pharmacokinetic features, innovative drug delivery systems, and chemical modifications. Through a rigorous analysis of peer-reviewed literature, we reveal that chrysin exerts its therapeutic effects predominantly by modulating key signaling pathways such as JAK/STAT3, NF-κB, and FOXM1/β-catenin. Despite a poor oral bioavailability, next-generation nano-platforms have demonstrated remarkable efficacy in enhancing bioavailability and targeted delivery, while structure-optimized derivatives further amplify their therapeutic index. By integrating current knowledge, this work not only provides a holistic overview of chrysin as a multifunctional bioactive compound but also identifies pressing challenges. Targeted research in these areas is imperative to unlock the full translational potential of chrysin for clinical applications.