Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating...

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.