Abstract

Understanding the mechanism behind neuronal regeneration is critical for treating ischemic stroke and traumatic brain injury. The presence of neural stem cells in and around the sub-ventricular zone of human and also in zebrafish is evidenced. In this current study, the neuro-protective potential of nano-formulated hesperetin on injury-induced neurogenesis in zebrafish was assessed. Nanoformulation of hesperetin was prepared by anti-solvent precipitation technique using sodium dodecyl sulfate (SDS) as the stabilizing agent. The synthesized particles were characterized using SEM, DLS, XRD and FT-IR. Anti-oxidant capacity of nano hesperetin (nHST) in in vitro followed by in vivo studies in a traumatic brain injury (TBI) model of adult zebrafish (Danio rerio), catalase activity, histological analysis and gene expression studies for the genes Sox2, Nestin, Fabp7a and HuC were carried out. The synthesized particles were found to be in nanoscale and SDS had successfully integrated with hesperetin. Moreover, nHST had a significantly higher anti-oxidant capacity in vitro. Catalase levels in nHST treated group were significantly restored compared to other groups. Histological studies supported reduced tissue damage on oral administration of nano-hesperetin as compared to other groups. Gene expression studies showed that nano-hesperetin at a concentration of 10 μM when administered orally induced proliferation of neural stem cells without inducing cell death.

摘要

了解神经元再生背后的机制对于治疗缺血性中风和创伤性脑损伤至关重要。证实了在人类心室下区及其周围以及斑马鱼中存在神经干细胞。在目前的这项研究中，评估了纳米配制的橙皮素对斑马鱼损伤诱导的神经发生的神经保护潜力。以十二烷基硫酸钠（SDS）为稳定剂，采用反溶剂沉淀技术制备橙皮素纳米制剂。使用 SEM、DLS、XRD 和 FT-IR 对合成的颗粒进行表征。纳米橙皮素 (nHST)在体外的抗氧化能力，随后在成年斑马鱼 ( Danio rerio ) 的创伤性脑损伤 (TBI) 模型中进行体内研究)，对基因Sox2、Nestin、Fabp7a和HuC进行过氧化氢酶活性、组织学分析和基因表达研究。发现合成的颗粒是纳米级的，SDS 已成功与橙皮素结合。此外，nHST在体外具有显着更高的抗氧化能力。与其他组相比，nHST 治疗组的过氧化氢酶水平显着恢复。组织学研究支持与其他组相比，口服纳米橙皮素可减少组织损伤。基因表达研究表明，当口服给药浓度为 10 μM 的纳米橙皮素时，可诱导神经干细胞增殖而不诱导细胞死亡。