Recent Advances in the Application of Natural Flavonoids in the Pharmaceutical Field

Natural flavonoids are widely distributed plant polyphenols that have attracted increasing attention as potential pharmaceutical agents because of their diverse biological activities. This review summarizes recent advances in the pharmacological activities, therapeutic applications, and translational challenges of natural flavonoids. Current evidence indicates that flavonoids can exert antioxidant effects through direct reactive oxygen species scavenging and regulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway, while their anti-inflammatory actions involve pathways such as nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). Several flavonoids also show antitumor potential by influencing apoptosis, cell proliferation, angiogenesis, and signaling pathways, including the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway and the Wingless-related integration site (Wnt)/β-catenin pathway. Their potential applications have been investigated in cardiovascular diseases, neurodegenerative disorders, diabetes, and other metabolic conditions. However, many findings are still based on cell and animal studies, and clinical translation remains limited by poor water solubility, low stability, extensive metabolism, weak systemic absorption, and variation among studies. Emerging delivery approaches, including nanocarriers and other formulation strategies, may improve flavonoid stability and bioavailability. Future research should emphasize standardized pharmacokinetic evaluation, safety assessment, quality control, and well-designed clinical trials to clarify therapeutic efficacy and support the development of reliable flavonoid-based pharmaceutical products.