Parthenolide ameliorates bilirubin-induced neuronal cell injury by mediating autophagy.

Abstract

Unconjugated bilirubin (UCB) induces neurotoxicity in newborns, yet effective interventions remain limited. This study explores the neuroprotective role and mechanisms of parthenolide (PRT) using both in vivo and in vitro models. Primary rat neuronal cells exposed to UCB were evaluated through CCK-8, flow cytometry, Western blot, and immunofluorescence assays. Additionally, a rat model of bilirubin encephalopathy was established via bilirubin injection to verify PRT's effects in vivo. The results indicated that UCB significantly suppressed autophagy, increased LDH release and apoptosis, and reduced cell viability. PRT treatment effectively attenuated UCB-induced neuronal injury by enhancing autophagic activity. Mechanistically, PRT mediated these protective effects through inhibition of the AKT/mTOR pathway. These findings demonstrate that PRT exerts notable neuroprotective properties and may serve as a promising therapeutic candidate for bilirubin encephalopathy.