Dl‐3‐n‐Butylphthalide Inhibits Autophagy to Alleviate the Neuronal Apoptosis After Spinal Cord Injury by Elevating YAP via Inactivating the Hippo Signaling Pathway

ABSTRACT Dl‐3‐n‐Butylphthalide (NBP) has been reported to relieve neuronal damage by suppressing excessive autophagy. This study explored whether NBP could protect neurons after spinal cord injury (SCI) by inhibiting excessive autophagy, and its intrinsic mechanism were investigated. In methodology, this paper detected the Hippo/YAP pathway activity and autophagy in peripheral blood of SCI patients. A SCI cell model and a rat SCI model were established. Through a series of assays and experimental validation, the effect and mechanism of NBP on neuronal damage after SCI were analyzed. As a result, the activated Hippo pathway, decreased YAP protein, and increased p‐YAP, Beclin 1, and LC3 II/I proteins were monitored in peripheral blood of SCI patients. OGD treatment enhanced apoptosis and autophagy, activated the Hippo/YAP pathway, and enhanced YAP nuclear translocation in PC12 cells. NBP treatment eliminated these effects of OGD on PC12 cells. YAP silencing reversed the suppression of NBP on the OGD‐induced PC12 cell apoptosis and autophagy. In vivo, the inhibition of NBP on neuronal injury, the Hippo/YAP pathway activity, and autophagy was abolished by YAP silencing. Thus, NBP attenuates autophagy to alleviate neuronal apoptosis after SCI via inactivating the Hippo/YAP pathway. NBP may be useful in SCI treatment clinically.