Ginkgolide B regulates apoptosis, oxidative stress, and mitochondrial dysfunction in MPP+-induced SK-N-SH cells by targeting HDAC4/JNK pathway

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.

Ginkgolide B; HDAC4; JNK pathway; MPP+ toxicity; Neuronal damage.