The protective effects of Ramelteon against 6‐OHDA‐induced cellular senescence in human SH‐SY5Y neuronal cells

BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a severe neurodegenerative disease with high morbidity in the elderly population. 6‐OHDA‐induced cell senescence is reported to be involved in the pathogenesis of PD. Ramelteon is an oral hypnotic agent that specifically targets the receptors of the suprachiasmatic nucleus in the human hypothalamus. Here, an investigation is made to see whether Ramelteon possesses a beneficial effect against 6‐OHDA‐induced cellular senescence in human SH‐SY5Y neuronal cells. METHODS: The release of LDH was detected to assess cytotoxicity and flow cytometry was conducted to evaluate the cell cycle. The telomerase activity and the SA‐β‐Gal assay were performed to determine the state of cell senescence. Oxidative stress was evaluated by detecting the release of H(2)O(2). The expressions of p21, p53, and Nrf2 were measured using the qRT‐PCR and Western blotting assay. siRNA technology was used to knock down the expression level of Nrf2 in SH‐SY5Y neuronal cells. RESULTS: First, it was found that Ramelteon mitigated cell cycle arrest in the G0/G1 phase in 6‐OHDA‐challenged SH‐SY5Y neuronal cells. Second, treatment with Ramelteon alleviated cellular senescence in 6‐OHDA‐treated SH‐SY5Y neuronal cells by increasing telomerase activity and reducing the activity of SA‐β‐gal. It was also found that Ramelteon reduced the expressions of p21 and p53. Notably, Ramelteon attenuated 6‐OHDA‐induced oxidative stress by increasing the expression of Nrf2. Silencing of Nrf2 abolished the protective effects of Ramelteon against 6‐OHDA‐induced cellular senescence. Based on these findings, it was concluded that Ramelteon alleviated 6‐OHDA‐induced cellular senescence by increasing the expression of Nrf2 in human SH‐SY5Y neuronal cells. CONCLUSION: Ramelteon protected against 6‐OHDA‐induced cellular senescence in human SH‐SY5Y neuronal cells through activating the Nrf2 signaling pathway.