Lignans from Eucommia ulmoides Oliver leaves exhibit neuroprotective effects via activation of the PI3K/Akt/GSK-3β/Nrf2 signaling pathways in H2O2-treated PC-12 cells

•Twelve neuroprotective compounds were isolated from E. ulmoides Oliv. leaves.•Diepoxylignans showed significantly neuroprotection.•(–)−7‑epi-Pinoresinol mr1 (1), (+)-medioresinol (2), and (+)-diapinoresinol (4) increased the cell viability, and the enzyme activity of SOD and GPx.•(–)−7‑epi-Pinoresinol mr1 (1), (+)-medioresinol (2), and (+)-diapinoresinol (4) reduced the level of ROS and LDH.•(–)−7‑epi-Pinoresinol mr1 (1), (+)-medioresinol (2), and (+)-diapinoresinol (4) regulated the PI3K/AKT/GSK-3β/Nrf2 signaling pathways.