Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Icariside II (ICS II) is known to confer notable therapeutic effects against a variety of neurodegenerative diseases, such as AD. Therefore, the present study aimed to evaluate the possible effects of ICS II on 1-methyl-4-phenylpyridinium (MPP+)-induced SK-N-SH cell injury, in addition to understanding the underlying mechanism of action. The MPP+-induced SK-N-SH cell model was used to simulate PD in vitro. The viability and mitochondrial membrane potential of SK-N-SH cells were detected by MTT assay and JC-1 staining, respectively. Lactate dehydrogenase (LDH) release, ATP levels and complex I activity in treated SK-N-SH cells were measured using LDH activity, ATP and Complex I assay kits, respectively. The protein expression levels of histone deacetylase 2 (HDAC2) and γ-H2A histone family member X and the copy number of mitochondrial DNA were measured by western blotting or reverse transcription-quantitative PCR, respectively. Autodock 4.2 was used to predict the molecular docking site of ICS II on HDAC2. The results of the present study demonstrated that ICS II mitigated SK-N-SH cytotoxicity induced by MPP+. Specifically, ICS II alleviated DNA damage and restored mitochondrial function in SK-N-SH cells treated with MPP+. In addition, ICS II reduced the HDAC2 protein expression levels in MPP+-induced SK-N-SH cells. However, overexpression of HDAC2 reversed the protective effects of ICS II on DNA damage and mitochondrial dysfunction in MPP+-induced SK-N-SH cells. In conclusion, the results of the present study suggest that ICS II can protect dopaminergic neurons from MPP+-induced neurotoxicity by downregulating HDAC2 expression to restore mitochondrial function.