Ding Xu, Tan Dongming, Wang Zhao, Yin Hongying
School of Traditional Chinese Medicine, Jiangsu College of Nursing, No. 9 Keji Avenue, Huai'an City, Jiangsu Province, China.
Huai'an Hospital Affiliated to Yangzhou University, The Fifth People's Hospital of Huai'an), 1 Huaihe East Road, Huaiyin District, Huai'an City, Jiangsu Province, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 29. doi: 10.1007/s00210-025-03815-7.
Ginkgolide B (GB) is a bioactive constituent found in Ginkgo biloba leaves that has been long recognized as a protective agent against many neurological disorders. Our study aimed to examine the effect of GB in an in vitro Parkinson's disease (PD) model and to investigate its neuroprotective mechanism as a primary objective. SK-N-SH cells were challenged with 1-methyl-4-phenylpyridinium (MPP) to act as a PD-like model of neuronal damage. CCK-8 method, flow cytometry assay, and fluorescent probe JC-1 respectively measured cell viability, apoptosis, and mitochondrial membrane potential (MMP). Oxidative stress parameters were examined with assay kits. Nicotinamide adenine dinucleotide phosphate level and adenosine triphosphate (ATP) synthesis were also appraised. RT-qPCR examined mitochondrial DNA (mtDNA) release. Western blotting analyzed the proteins implicated in apoptosis and the histone deacetylase 4 (HDAC4)/Jun N-terminal kinase (JNK) pathway. GB concentration-dependently alleviated MPP-stimulated viability loss, apoptosis, oxidative stress, and mitochondrial dysfunction in SK-N-SH cells. GB docked with HDAC4 and downregulated the HDAC4/JNK pathway. HDAC4 overexpression further reduced the viability and aggravated apoptosis, oxidative stress, and mitochondrial dysfunction in GB-treated SK-N-SH cells challenged with MPP. Altogether, GB might inactivate the HDAC4/JNK pathway to protect against MPP-triggered neuronal damage in PD.
银杏内酯B（GB）是银杏叶中发现的一种生物活性成分，长期以来一直被认为是多种神经疾病的保护剂。我们的研究旨在检测GB在体外帕金森病（PD）模型中的作用，并将其神经保护机制作为主要目标进行研究。用1-甲基-4-苯基吡啶鎓（MPP）处理SK-N-SH细胞，以建立类似PD的神经损伤模型。采用CCK-8法、流式细胞术和荧光探针JC-1分别检测细胞活力、凋亡和线粒体膜电位（MMP）。用试剂盒检测氧化应激参数。还评估了烟酰胺腺嘌呤二核苷酸磷酸水平和三磷酸腺苷（ATP）合成。RT-qPCR检测线粒体DNA（mtDNA）释放。蛋白质印迹法分析凋亡相关蛋白以及组蛋白去乙酰化酶4（HDAC4）/Jun氨基末端激酶（JNK）通路。GB呈浓度依赖性地减轻MPP刺激引起的SK-N-SH细胞活力丧失、凋亡、氧化应激和线粒体功能障碍。GB与HDAC4结合并下调HDAC4/JNK通路。HDAC4过表达进一步降低了用MPP处理的GB处理的SK-N-SH细胞的活力，并加重了凋亡、氧化应激和线粒体功能障碍。总之，GB可能使HDAC4/JNK通路失活，以保护免受MPP引发的PD神经元损伤。
