This study aims to investigate the mechanism of the regulation of oxygen-glucose deprivation (OGD) in PC12 cells by schisanlactone E (SE) via phosphatase and tensin homolog (PTEN)/mammalian target of rapamycinm (mTOR)/hypoxia-inducible factor 1α(HIF-1α) pathway.OGD-PC12 cells models were constructed in vitro,which were divided into control group (Con),OGD group,SE group,bisperoxovanadium (Bpv) group,and Bpv+SE group.Relevant indexes were detected by thiazolyl blue staining (MTT) method,flow cytometry,transmission electron microscopy,monodansylcadaverine (MDC),and western blot.The results indicated that,compared to the OGD group,the SE group exhibited a marked improvement in cell survival rate (P<0.01) and a corresponding decrease in apoptosis rate (P<0.01),both the SE and Bpv groups showed a reduction in the number of autophagosomes and lysosomes (P<0.01),as well as a diminished fluorescence intensity of autophagosomes (P<0.01),there was an elevation in the expression levels of sequestosome1 (p62) and p-mammalian target of rapamycinm (p-mTOR)/mTOR proteins (P<0.01 or P<0.05),the microtubule-associated protein1 light chain 3-II/I (LC3-II/LC3-I),recombinant beclin1(Beclin1),PTEN,and HIF-1α protein levels were significantly decreased (P<0.01).The Bpv+SE group showed a decrease in the number of autophagosomes and lysosomes compared to the Bpv group (P<001),the fluorescence intensity of autophagosomes also decreased (P<0.01),while the expression levels of p62 and p-mTOR/mTOR proteins increased (P<0.01 or P<0.05).Additionally,the expression levels of LC3-II/LC3-I,Beclin1,PTEN,and HIF-1α proteins decreased (P<0.01).At a concentration of 0.1 μmol/L,SE can achieve the optimal effect in protecting neurons from autophagic injury and exert an inhibitory effect on OGD-PC12 cell autophagic damage.By adding PTEN inhibitor,mTOR can be upregulated,leading to downregulation of HIF-1α.The combined use of SE and PTEN inhibitor shows more significant effects.This study can provide a certain experimental basis for the research and development of local natural ethnic products SE and its molecular mechanism against ischemic stroke (IS) ischemic injury.It also accumulates experience in serving human health with local ethnic natural products and promoting local economic development.