Hyperoside has a variety of pharmacological activities, including anti-liver injury, anti-depression, anti-inflammatory, and anti-cancer activities. However, the effect of hyperoside on Parkinson’s disease (PD) is still unclear. Therefore, we tried to study the therapeutic effect and mechanism of hyperoside on PD in vivo and in vitro models. Rotenone was used to induce PD rat model and SH-SY5Y cell injury model, and hyperoside was used for intervention. Immunohistochemistry, animal behavior assays, TUNEL and Western blot were constructed to observe the protective effect and related mechanisms of hyperoside in vivo. Cell counting kit-8 (CCK-8), flow cytometry, Rh123 staining and Western blot were used for in vitro assays. Rapamycin (RAP) pretreatment was used in rescue experiments to verify the relationship between hyperoside and autophagy in rotenone-induced SH-SY5Y cells. Hyperoside promoted the number of tyrosine hydroxylase (TH)-positive cells, improved the behavioral defects of rats, and inhibited cell apoptosis in vivo. Different concentrations of hyperoside had no significant effect on SH-SY5Y cell viability, but dramatically reversed the rotenone-induced decrease in cell viability, increased apoptosis and loss of cell mitochondrial membrane potential in vitro. Additionally, hyperoside reversed the regulation of rotenone on the Beclin1, LC3II, Bax, cleaved caspase 3, Cyc and Bcl-2 expressions in rat SNpc tissues and SH-SY5Y cells, while promoted the regulation of rotenone on the P62 and α-synuclcin. Furthermore, RAP reversed the effect of hyperoside on rotenone-induced SH-SY5Y cells. Hyperoside may play a neuroprotective effect in rotenone-induced PD rat model and SH-SY5Y cell model by affecting autophagy.

金丝桃苷具有多种药理活性，包括抗肝损伤、抗抑郁、抗炎和抗癌活性。然而，金丝桃苷对帕金森病（PD）的作用仍不清楚。因此，我们试图在体内和体外模型中研究金丝桃苷对PD的治疗作用和机制。采用鱼藤酮诱导PD大鼠模型和SH-SY5Y细胞损伤模型，并采用金丝桃苷进行干预。采用免疫组织化学、动物行为学、TUNEL和Western blot等方法观察金丝桃苷的体内保护作用及相关机制。使用细胞计数试剂盒-8 (CCK-8)、流式细胞术、Rh123 染色和蛋白质印迹进行体外测定。采用雷帕霉素（RAP）预处理进行拯救实验，验证鱼藤酮诱导的SH-SY5Y细胞中金丝桃苷与自噬的关系。金丝桃苷在体内促进酪氨酸羟化酶（TH）阳性细胞的数量，改善大鼠的行为缺陷，并抑制细胞凋亡。不同浓度的金丝桃苷对SH-SY5Y细胞活力没有显着影响，但在体外显着逆转鱼藤酮诱导的细胞活力下降、细胞凋亡增加和细胞线粒体膜电位丧失。此外，金丝桃苷还逆转了鱼藤酮对大鼠SNpc组织和SH-SY5Y细胞中Beclin1、LC3II、Bax、cleaved caspase 3、Cyc和Bcl-2表达的调节，同时促进了鱼藤酮对P62和α-突触核蛋白的调节。此外，RAP 逆转了金丝桃苷对鱼藤酮诱导的 SH-SY5Y 细胞的影响。金丝桃苷可能通过影响自噬在鱼藤酮诱导的PD大鼠模型和SH-SY5Y细胞模型中发挥神经保护作用。