This study aims to investigate the protective effects of mogroside V (Mog V) in dopaminergic neurons against the inflammatory damage caused by microglia activation and its related mechanism.Dopaminergic neurons (MN9D cells) and microglia (BV-2 cells) were co-cultured in Transwell plate,and lipopolysaccharide was added to activate microglia to establish an inflammatory model in vitro.MN9D cells were divided into the control group,model group and Mog V group.MN9D cells in the Mog V group were treated with 50 μmol/L Mog V for 48 h based on the model group.Flow cytometry was used to test cell apoptosis rate and cell cycle distribution,JC-1 method was used to detect the changes in mitochondrial membrane potential,and the opening of mitochondrial permeability transition pores (mPTP) was analyzed by co-incubation of calcein-AM and CoCl₂.Fluorescent probe DCFH-DA was used to analyze the intracellular reactive oxygen species (ROS) levels and Western blot was used to test protein levels.The results showed that,compared with those of control group,inflammatory injury significantly increased the cell apoptosis rate,reduced the proportion of S-phase cells and mitochondrial membrane potential,increased the mPTP opening and ROS generation,decreased the protein expression of SIRT3,superoxide dismutase 2 (SOD₂) and Bcl-2,and significantly increased the protein expression of Bax and Caspase-3 of dopaminergic neuron MN9D cells in the model group,and the differences between the two groups were statistically significant (all P<0.05).Compared with the model group,Mog V treatment decreased the apoptosis rate of dopaminergic neurons,increased the proportion of S-phase cells and mitochondrial membrane potential,reduced the mPTP opening and ROS production,significantly increased the protein levels of SIRT3,SOD₂ and Bcl-2,and significantly decreased the protein levels of Bax and Caspase-3 of MN9D cells in the Mog V group,and the differences between the two groups were statistically significant (all P<0.05).The above results indicate that Mog V can inhibit the apoptosis and cell cycle arrest of dopaminergic neurons induced by microglia activation,and alleviate the neuroinflammatory injury to some extent.The mechanism may be related to its promotion of SIRT3 protein expression and improvement of mitochondrial function.