Comprehensive Review on Naringenin: A Potential Flavonoid

Naringenin, a flavonoid abundant in citrus fruits, is known for its diverse pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, and anti-cancer effects. These therapeutic actions are primarily mediated through modulation of key cellular pathways such as NF-κB, Nrf2, and PI3K/AKT. Despite its promising bioactivity, naringenin's clinical utility is limited by its poor aqueous solubility, hydrophobicity, and extensive first-pass hepatic metabolism, resulting in low oral bioavailability. This review focuses on evaluating naringenin's physicochemical and pharmacokinetic characteristics, mechanisms of action, and reported toxicity profile. It also discusses the role of naringenin glycosides and how they may influence absorption and metabolic fate. The manuscript highlights current challenges in naringenin delivery and explores advanced formulation strategies—including nanoencapsulation, solid lipid nanoparticles, and liposomes—that aim to enhance its solubility, stability, and targeted bioavailability. Recent clinical trials investigating naringenin's efficacy in managing hyperlipidemia, neurodegenerative disorders, and inflammatory diseases are summarized, emphasizing their design, application routes, and strategies to overcome bioavailability constraints. Though preclinical data are promising, limited human studies and a lack of long-term safety assessments remain key research gaps. In conclusion, while naringenin represents a promising candidate for therapeutic development, translational progress requires a deeper understanding of its metabolic behaviour and the implementation of efficient drug delivery systems. This review offers a consolidated foundation for future research and formulation design focused on maximizing the clinical potential of naringenin.