Effects of orientin on motor dysfunction and survival of dopaminergic neurons in mice with Parkinson's disease and its mechanism study

TANG Xiuling; GAO Ying; YANG Le

doi:10.13276/j.issn.2097-1656.2025.03.012

Abstract：Objective To explore the effect of orientin on MPTP-induced Parkinson's disease(PD)and its related mechanisms.Methods MPTP and MPP+were used to induce PD models in vivo(C57BL/6 mice)and in vitro(SH-SY5Y cells).Behavioral tests were used to evaluate the exercise ability of mice,immunofluorescence staining was used to observe the number of dopaminergic neurons in mice.CCK-8 method was used to detect cell viability,and flow cytometry was used to detect cell apoptosis and reactive oxygen species.The levels of SOD,MDA,and other oxidative stress indicators in SH-SY5Y cells were detected by corresponding kits,and the mitochondrial membrane potential was detected by fluorescent probe JC-1.Western blotting was used to detect the expression of Akt/Nrf2/HO-1 pathway proteins and apoptosis-related proteins.Results Compared with MPTP group,orientin improved motor dysfunction and reduced the loss of substantia nigra dopaminergic neurons in PD mice(P＜0.05).Compared with MPP+model group,orientin increased cell viability(P＜0.05),decreased apoptosis rate(P＜0.01),lowered the oxidative stress level of cells(P＜0.05),reduced mitochondrial membrane potential damage(P＜0.05),restored the protein level of Akt/Nrf2/HO-1 pathway,decreased the expression of apoptosis-related proteins Bax and Caspase 3(P＜0.05),and increased the expression of Bcl-2(P＜0.01).Conclusion Orientin has a significant improvement effect on MPTP-induced PD,and mitigate the apoptosis of dopaminergic neurons induced by MPP+/MPTP.The underlying mechanism may be related to activation of Akt/Nrf2/HO-1 pathway,suppression of oxidative stress,and attenuation of mitochondrial damage.