〔Abstract〕 Objective To study the effect of formononetin on the cell damage of glucose/oxygen deprivation/reoxygenation glyconeuronsviathe PARP1 signaling pathway, and to offer theoretical support for the use of Caragana isoflavones in the treatment of cerebral ischemia-reperfusion injury. Methods In mouse neurons(HT22), a model of Oxygen-glucose deprivation/reoxygenation(OGD/R) was created. Western blot was used to detect the expression of PARP1 and PARG in HT22 neurons at various time points of glucose-oxygen deprivation/reoxygenation, and the optimal time point of pathway modification was chosen. After OGD/R, HT22 cells were treated with formononetin, PARP1 inhibitor(PJ34), and PARG inhibitor, and six groups were developed: control group, control group+formononetin group, OGD/R group, OGD/R+ formononetin group, OGD/R+PJ34 group, OGD/R+PARG inhibitor group. HT22 cells were grown normally without OGD/R therapy in the control group. The expression levels of apoptotic factors and associated proteins in each group were determined using immunofluorescence and Western blot. Results PARP1 pathway was activated most obviously in HT22 cells after 3 hours of glucose and oxygen deprivation/reoxygenation. Under the condition of OGD/R 3 h, treatment with formononetin, PJ34 or PARG inhibitor could increase E3 ubiquitin ligase(Iduna), inhibit the expression of PARP1 and PARG pathway proteins, reduce the expression of AIF and P53, and increase the phosphorylation level of AKT protein. Conclusion Formononetin can block the PARP1/AIF/Akt signaling pathway by raising the expression of Iduna protein in the presence of OGD/R, hence decreasing the damage to HT22 mouse neurons.