Naringenin: A Promising Flavonoid with Therapeutic Potential, Bioavailability Challenges and Advanced Drug Delivery Approaches

Abstract

Naringenin, a naturally occurring flavonoid mainly present in citrus fruits, has attracted considerable scientific interest due to its diverse pharmacological and therapeutic properties. It exhibits significant antioxidant, anti-inflammatory, anticancer, antidiabetic, antimicrobial, antiviral, hepatoprotective, cardioprotective, and neuroprotective activities through its interaction with multiple cellular and molecular targets. The unique chemical structure of Naringenin contributes to its broad spectrum of biological effects, making it a promising candidate for the management of various chronic and metabolic disorders. However, its clinical application is greatly restricted because of poor aqueous solubility, limited permeability, extensive first-pass metabolism, and low oral bioavailability. To overcome these limitations, several advanced drug delivery systems, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, nanosuspensions, and self-nanoemulsifying drug delivery systems, have been developed to enhance its stability, bioavailability, and targeted delivery. Although these nano formulations improve therapeutic efficacy, concerns regarding toxicity, safety, dosage optimization, and long-term clinical use remain important considerations. This review provides a comprehensive overview of the chemistry, pharmacokinetic profile, bioavailability challenges, pharmacological activities, and novel drug delivery approaches of Naringenin. In addition, recent clinical investigations and future perspectives for its therapeutic application are also discussed.