Intervertebral disc degeneration (IVDD) is closely associated with inflammatory environments. Curcumol has been shown to alleviate inflammation in various disease models, but its effects on IVDD remain unclear. In this study, we sought to determine the mechanism of curcumol in TNF-α-induced nucleus pulposus cells (NPCs) and a mouse IVDD model.NPCs were pretreated with curcumol and then exposed to TNF-α. Cell viability was analyzed using the CCK-8, and the mRNA and protein levels of inflammatory cytokines and PI3K/Akt/NF-κB-related signaling molecules were detected using RT-PCR, ELISA and western blotting. The mouse IVDD model was established by puncturing the C6/7 level of the caudal spine, and treated with curcumol after surgery. ABOG staining were performed to evaluate the severity intervertebral disc damage, and immunohistochemistry(IHC) was performed to detect the expression of TNF-α. The toxicological effects of curcumol were measured by performing HE staining and ELISA.Curcumol reduced IL-1β, IL-6 and TNF-α production in NPCs, and the phosphorylation of proteins in the PI3K/Akt/NF-κB signaling pathway was also decreased. The PI3K/Akt/NF-κB -related signaling molecules decreased when TNF-α-induced NPCs were treated with a PI3K inhibitor; however, curcumol did not reverse these effects. In vivo, curcumol ameliorated the progression of IVDD at the early stage and did not exert toxicological effects.These results suggest a potential therapeutic use of curcumol to alleviate inflammation via the PI3K/Akt/NF-κB signaling pathway and delay the progression of IVDD.Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.