Abstract Context Hydroxysafflor yellow A (HSYA) has been shown to have neuroprotective effects in cerebral infarction. However, its underlying roles in apoptosis and inflammation in Parkinson’s disease (PD) are unknown. Objective The present study investigates the effects and underlying mechanisms of HSYA on dopaminergic (DA) neurodegeneration, inflammation, and apoptosis. Materials and methods The PD model was established by 2 μL of 6-hyroxydopamine (6-OHDA) (3 μg/μL) striatal injection in C57BL/6J mice with different doses of HSYA (2, 4, or 8 mg/kg). In vitro, after being treated with HSYA for 1 h, SH-SY5Y cells were exposed to 6-OHDA for 24 h before analysis. Expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and corpus striatum (STR) was evaluated by immunohistochemistry (IHC) and western blot. In addition, apoptosis-related and inflammatory proteins were examined by western blot. Results Administration of HSYA significantly reduced the Apomorphine (APO)-induced rotation, decreased from 122.5 ± 15.1 (6-OHDA group) to 47.2 ± 14.3 (8 mg/kg HSYA group). HSYA partially restored a deficit in the SN and STR of PD mice brains in TH. Furthermore, western blot analysis revealed that HSYA reduced inflammatory proteins, including iNOS, COX-2 and NF-κB and attenuated the elevation of DA neuronal apoptosis observed in PD. In vitro assays showed that HSYA reduced the levels of p-p38 and p-JNK and increased that of p-ERK in 6-OHDA-leisoned SH-SY5Y cells. Conclusions These findings indicate that HSYA protects against 6-OHDA induced DA neurodegeneration partly by regulating the MAPK inflammatory signalling pathway and apoptosis which highlight its therapeutic potential in the treatment of PD.

中文翻译：

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羟基红花黄A对多巴胺能神经元6-羟基多巴胺的保护作用，激活抗凋亡和抗神经炎症通路

摘要背景 羟基红花黄 A (HSYA) 已被证明对脑梗塞具有神经保护作用。然而，其在帕金森病 (PD) 的细胞凋亡和炎症中的潜在作用尚不清楚。目的本研究探讨HSYA对多巴胺能(DA)神经变性、炎症和细胞凋亡的影响及其潜在机制。材料和方法 通过在 C57BL/6J 小鼠中注射 2 μL 6-羟基多巴胺 (6-OHDA) (3 μg/μL) 纹状体，使用不同剂量的 HSYA（2、4 或 8 mg/kg）建立 PD 模型。在体外，用 HSYA 处理 1 小时后，SH-SY5Y 细胞在分析前暴露于 6-OHDA 24 小时。通过免疫组织化学 (IHC) 和蛋白质印迹评估酪氨酸羟化酶 (TH) 在黑质 (SN) 和纹状体 (STR) 中的表达。此外，通过蛋白质印迹检查细胞凋亡相关蛋白和炎症蛋白。结果 HSYA 的给药显着降低了阿扑吗啡 (APO) 诱导的旋转，从 122.5 ± 15.1（6-OHDA 组）降至 47.2 ± 14.3（8 mg/kg HSYA 组）。HSYA 部分恢复了 TH 中 PD 小鼠大脑的 SN 和 STR 缺陷。此外，蛋白质印迹分析显示，HSYA 减少炎症蛋白，包括 iNOS、COX-2 和 NF-κB，并减弱 PD 中观察到的 DA 神经元凋亡的升高。体外测定表明，HSYA 降低了 p-p38 和 p-JNK 的水平，并增加了 6-OHDA 感染的 SH-SY5Y 细胞中 p-ERK 的水平。