Neuroprotective effect of naringenin-loaded solid lipid nanoparticles against streptozocin-induced neurotoxicity through autophagy blockage
Zeinab Nouri
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Conceptualization, Investigation, Methodology, Writing - original draft, Writing - review & editing
Search for more papers by this authorSoraya Sajadimajd
Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran
Contribution: Conceptualization, Methodology, Writing - review & editing
Search for more papers by this authorLeila Hoseinzadeh
Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Writing - review & editing
Search for more papers by this authorGholamreza Bahrami
Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Writing - review & editing
Search for more papers by this authorElham Arkan
Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Writing - review & editing
Search for more papers by this authorSajad Moradi
Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorFereshteh Abdi
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Investigation
Search for more papers by this authorCorresponding Author
Mohammad Hosein Farzaei
Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Correspondence
Mohammad Hosein Farzaei, Pharmaceutical Sciences Research Center, Kermanshah University of Medical, Sciences, Kermanshah, Iran.
Email: [email protected]
Contribution: Conceptualization, Supervision, Writing - review & editing
Search for more papers by this authorZeinab Nouri
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Conceptualization, Investigation, Methodology, Writing - original draft, Writing - review & editing
Search for more papers by this authorSoraya Sajadimajd
Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran
Contribution: Conceptualization, Methodology, Writing - review & editing
Search for more papers by this authorLeila Hoseinzadeh
Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Writing - review & editing
Search for more papers by this authorGholamreza Bahrami
Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Writing - review & editing
Search for more papers by this authorElham Arkan
Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Writing - review & editing
Search for more papers by this authorSajad Moradi
Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorFereshteh Abdi
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
Contribution: Investigation
Search for more papers by this authorCorresponding Author
Mohammad Hosein Farzaei
Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Correspondence
Mohammad Hosein Farzaei, Pharmaceutical Sciences Research Center, Kermanshah University of Medical, Sciences, Kermanshah, Iran.
Email: [email protected]
Contribution: Conceptualization, Supervision, Writing - review & editing
Search for more papers by this authorZeinab Nouri and Soraya Sajadimajd contributed equally to this work.
Abstract
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.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest regarding the publication of this paper.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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