Neuroprotective effect of naringenin-loaded solid lipid nanoparticles against streptozocin-induced neurotoxicity through autophagy blockage.

Autophagy is a pivotal contributing factor to modulate the progression of neurodegenerative diseases. Although naringenin (Nar) has shown beneficial effects against neurodegenerative diseases, its poor solubility and bioavailability have limited its application. The present research aimed to design a nanostructured formulation of Nar to achieve an enhanced therapeutic effect. Herein, Nar-loaded solid lipid nanoparticles (Nar-SLNs) were prepared and characterized. Then, PC12 cells were exposed to streptozocin (STZ) and/or Nar and Nar-SLNs in vitro to clarify the protective effect of Nar and its nanoformulation against STZ-stimulated neurotoxicity. The empty SLNs and Nar-SLNs indicated a narrow polydispersity index value with a negative zeta potential. As determined by the scanning electron microscopy images, the nanoparticles had a spherical shape and were less than 20 nm in size. FTIR results demonstrated the interaction between Nar and SLNs and supported the presence of Nar in the nanoparticle. The nanoformulation revealed an initial burst release followed by a sustained release manner. Treatment of PC12 cells with STZ resulted in mitochondrial dysfunction and increased autophagic markers, including LC3-II, Beclin1, Akt, ATG genes, and accumulation of miR-21 and miR-22. Both Nar and Nar-SLNs pre-treatment improved cell survival and augmented mitochondrial membrane potential, accompanied by reduced autophagic markers expression. However, Nar-SLNs were more effective than free Nar. As a result, our findings suggested that SLNs effectively enhance the neuroprotective effect of Nar, and Nar-SLNs may be a promising candidate to suppress or prevent STZ-elicited neurotoxicity. PRACTICAL APPLICATIONS: According to the beneficial effect of Nar in the management of neurodegenerative diseases, we evaluated the protective effect of Nar and Nar-SLNs against STZ-stimulated neurotoxicity and analyzed the role of autophagy in STZ-stimulated neurotoxicity. Our results proposed that Nar-SLNs could be a promising option for neurological disorders prevention through autophagy suppression.