Protective potential of naringenin and its nanoformulations in redox mechanisms of injury and disease

Increasing evidence suggests that elevated intracellular levels of reactive oxygen species (ROS) play a significant role in the pathogenesis of many diseases. Increased intracellular levels of ROS can lead to the oxidation of lipids, DNA, and proteins, contributing to cellular damage. Hence, the maintenance of redox hemostasis is essential. Naringenin (NAR) is a flavonoid included in the flavanones subcategory. Various pharmacological actions have been ascribable to this phytochemical composition, including antioxidant, anti-inflammatory, antibacterial, antiviral, antitumor, antiadipogenic, neuro-, and cardio-protective activities. This review focused on the underlying mechanism responsible for the antioxidative stress properties of NAR and its' nanoformulations. Several lines of in vitro and in vivo investigations suggest the effects of NAR and its nanoformulation on their target cells via modulating signaling pathways. These nanoformulations include nanoemulsion, nanocarriers, solid lipid nanoparticles (SLN), and nanomicelle. This review also highlights several beneficial health effects of NAR nanoformulations on human diseases including brain disorders, cancer, rheumatoid arthritis, and small intestine injuries. Employing nanoformulation can improve the pharmacokinetic properties of NAR and consequently efficiency by reducing its limitations, such as low bioavailability. The protective effects of NAR and its' nanoformulations against oxidative stress may be linked to the modulation of Nrf2-heme oxygenase-1, NO/cGMP/potassium channel, COX-2, NF-kappa B, AMPK/SIRT3, PI3K/Akt/mTOR, BDNF, NOX, and LOX-1 pathways. Understanding the mechanism behind the protective effects of NAR can facilitate drug development for the treatment of oxidative stress-related disorders.