The depletion of dopamine in the striatum region and Lewy bodies are the hallmark characteristics of Parkinson’s disease. The pathology also includes the upregulation of various Parkinson’s disease (PARK) genes and kinases. Two such kinases, LRRK2 and GSK-3β have been directly implicated in the formation of tau and alpha-synuclein proteins, causing PD. Hesperidin (HES) is a flavanone glycoside that has multiple therapeutic benefits including neuroprotective effects. In this study, we examined the neuroprotective effects of HES against 6-hydroxydopamine (6−OHDA) induced-neurotoxicity in the in-vitro and in-vivo model. Hesperidin significantly protected the SH-SY5Y cells' stress against 6−OHDA induced toxicity by downregulating biomarkers of oxidative stress. Furthermore, HES downregulated the kinases lrrk2 and gsk3β along with casp3, casp9, and polg in the zebrafish model. The treatment with HES also improved the locomotor pattern of zebrafish that was affected by 6−OHDA. This study suggests that hesperidin could be a drug of choice in targeting kinases against a 6−OHDA model of PD.

纹状体区域和路易体中多巴胺的消耗是帕金森氏病的标志性特征。病理还包括各种帕金森氏病（PARK）基因和激酶的上调。两种此类激酶LRRK2和GSK-3β直接与tau和α-突触核蛋白蛋白的形成有关，从而导致PD。橙皮苷（HES）是一种黄烷酮苷，具有多种治疗作用，包括神经保护作用。在这项研究中，我们检查了HES的神经保护作用对6-羟基（6-OHDA）诱导的神经毒性在体外和在体内模型。橙皮苷通过下调氧化应激的生物标志物来显着保护SH-SY5Y细胞的应激免受6-OHDA诱导的毒性。此外，HES在斑马鱼模型中下调了激酶lrrk2和gsk3β以及casp3，casp9和polg。HES处理还改善了受6-OHDA影响的斑马鱼的运动模式。这项研究表明，橙皮苷可能是针对6-OHDA PD模型的激酶靶向药物的选择。