Nouri Zeinab, Sajadimajd Soraya, Hoseinzadeh Leila, Bahrami Gholamreza, Arkan Elham, Moradi Sajad, Abdi Fereshteh, Farzaei Mohammad Hosein
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.
J Food Biochem. 2022 Dec;46(12):e14408. doi: 10.1111/jfbc.14408. Epub 2022 Sep 21.
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.
自噬是调节神经退行性疾病进展的关键因素。尽管柚皮素（Nar）已显示出对神经退行性疾病的有益作用，但其溶解性和生物利用度差限制了其应用。本研究旨在设计一种纳米结构的柚皮素制剂，以增强其治疗效果。在此，制备并表征了载柚皮素的固体脂质纳米粒（Nar-SLNs）。然后，将PC12细胞在体外暴露于链脲佐菌素（STZ）和/或Nar及Nar-SLNs，以阐明Nar及其纳米制剂对STZ诱导的神经毒性的保护作用。空白SLNs和Nar-SLNs显示出窄的多分散指数值和负的zeta电位。通过扫描电子显微镜图像测定，纳米粒呈球形，尺寸小于20nm。傅里叶变换红外光谱（FTIR）结果证明了Nar与SLNs之间的相互作用，并支持纳米粒中存在Nar。该纳米制剂呈现出初始的突释，随后是缓释方式。用STZ处理PC12细胞导致线粒体功能障碍，并增加自噬标志物，包括LC3-II、Beclin1、Akt、自噬相关基因（ATG基因），以及miR-21和miR-22的积累。Nar和Nar-SLNs预处理均提高了细胞存活率并增强了线粒体膜电位，同时自噬标志物表达降低。然而，Nar-SLNs比游离Nar更有效。因此，我们的研究结果表明，SLNs有效地增强了Nar的神经保护作用，Nar-SLNs可能是抑制或预防STZ诱导的神经毒性的有前景的候选物。实际应用：根据Nar在神经退行性疾病管理中的有益作用，我们评估了Nar和Nar-SLNs对STZ诱导的神经毒性的保护作用，并分析了自噬在STZ诱导的神经毒性中的作用。我们的结果表明，Nar-SLNs可能是通过抑制自噬预防神经疾病的有前景的选择。
