Abstract：Objective：To discuss the effect of extract of ramulus mori on injury of SK-N-SH cells treated with 1-methyl- 4 phenylpyridine(MPP+) and its molecular mechanism. Methods：SK-N-SH cells were randomly divided into the control group without any treatment， the model group(2.5 mmol/L MPP + )， the low- dose， medium- dose， and high- dose medicine groups(20 μmol/L，40 μmol/L，and 60 μmol/L extract of ramulus mori+2.5 mmol/L MPP+)，the administration group(50 μmol/L selegiline as positive control+2.5 mmol/L MPP+)，the anti-miR-NC group(cells transfected with miR-369 inhibitor negative control+2.5 mmol/L MPP+)，the anti-miR-369 group(cells transfected with miR-369 inhibitor+2.5 mmol/L MPP+)，the highdose medicine group+ anti-miR- NC group(cells transfected with miR-369 inhibitor negative control+60 μmol/L extract of ramulus mori+2.5 mmol/L MPP+)，and the high-dose medicine group+anti-miR-369 group(cells transfected with miR-369 inhibitor+60 μmol/L extract of ramulus mori+2.5 mmol/L MPP + ). The cell survival rate was detected by cell counting kit 8 (CCK-8). Cell apoptosis was detected by flow cytometry. The expression of protein of cysteinyl aspartate specific proteinase-3 (Caspase3) was detected by Western blot method. The level of interleukin- 1β(IL- 1β) was detected by enzyme- linked immunosorbent assay(ELISA). The content of malondialdehyde(MDA) in cells and the activity of superoxide dismutase(SOD) were detected by kits. The expression levels of mRNA of miR-369 and protein kinase B1(AKT1) were detected by real-time fluorescence quantitative PCR(RT- qPCR). Luciferase expression vectors containing wild- type and mutant AKT1 were cotransfected into SK-N-SH cells with miR-NC and miR-369，respectively. The targeted relationship between miR-369 and AKT1 was detected by luciferase reporter assay. Results：In SK-N-SH cells treated with MPP+，cell survival rate，the SOD activity，and the expression level of mRNA of AKT1 were decreased；cell apoptosis rate，the expression levels of Caspase3 and miR-369，the IL-1β level，and the MDA content were increased(P＜0.05). After cells were treated with low- dose， medium- dose，and high- dose extract of ramulus mori，cell survival rate，the SOD activity，and the expression level of mRNA of AKT1 were increased；cell apoptosis rate，the expression levels of Caspase3 and miR-369，the IL-1β level，and the MDA content were decreased(P＜0.05). The inhibition of the miR- 369 expression can promote cell survival and SOD activity，suppress cell apoptosis and the release of inflammatory factor IL-1β，and reduce the MDA content. The inhibition of the miR-369 expression could strengthen the protective effect of extract of ramulus mori on SK- N- SH cells treated with MPP+. miR-369 was in the targeted regulation of AKT1. Conclusion：The extract of ramulus mori could inhibit cell apoptosis， inflammatory response and oxidative stress induced by MPP + in SK- N- SH cells. The extract of ramulus mori probably has protective effect on injury of SK-N-SH cells induced by MPP+ by regulating miR-369/AKT1.