Flavonolignans and biflavonoids from Cephalotaxus oliveri exert neuroprotective effect via Nrf2/ARE pathway

Plants of the Cephalotaxus genus are rich in structurally diverse and naturally bioactive components, while limited studies have been reported for Cephalotaxus oliveri. Two undescribed flavonolignans and four undescribed biflavonoids, as well as thirteen known compounds, were isolated from the twigs and leaves of C. oliveri. Their structures were characterized by spectroscopic data analysis, and the absolute configurations were determined by electronic circular dichroism (ECD) calculations. All the isolated compounds were assayed for their neuroprotective activity against hydrogen peroxide (H₂O₂)-induced SH-SY5Y cell injury. All six undescribed compounds were effective to some degree, and umcephabiflovin B, apigenin 5-O-α-L-rhamnopyranosyl-(1 → 2)-6″-acetyl-β-D-glucopyranoside, and apigenin 7-O-β-D-glucoside exhibited good neuroprotective activity. Umcephabiflovin B protected SH-SY5Y cells against H₂O₂-induced neurotoxicity by repressing oxidative stress and apoptosis and by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant-response element (ARE) pathway.