Curcumol Alleviates the Inflammation of Nucleus Pulposus Cells via the PI3K/Akt/NF-κB Signaling Pathway and Delays Intervertebral Disk Degeneration

• Published in: World neurosurgery 2021-11, Vol.155, p.e402-e411
• Main Authors: He, Shenghua, Fu, Yuanfei, Yan, Bona, Tan, Huangsheng, Li, Haokang, Li, Jin, Huang, Dan, Huang, Zhuohan, Lai, Juyi, Feng, Hualong, Sun, Zhitao, Lan, Zhiming
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Cell Survival - drug effects; Cell Survival - physiology; Curcumol; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Intervertebral Disc Degeneration - metabolism; Intervertebral Disc Degeneration - pathology; Intervertebral Disc Degeneration - prevention & control; Intervertebral disk degeneration; Male; Mice; Mice, Inbred C57BL; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Nucleus Pulposus - drug effects; Nucleus Pulposus - metabolism; Nucleus Pulposus - pathology; Nucleus pulposus cells; Phosphatidylinositol 3-Kinases - metabolism; Phosphoinositide-3 Kinase Inhibitors - pharmacology; Phosphoinositide-3 Kinase Inhibitors - therapeutic use; PI3K/Akt/NF-κB; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Rats; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Signal Transduction - drug effects; Signal Transduction - physiology
• ISSN: 1878-8750; 1878-8769
• DOI: 10.1016/j.wneu.2021.08.079

Intervertebral disk 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 tumor necrosis factor (TNF)-α−induced nucleus pulposus cells and a mouse IVDD model. Nucleus pulposus cells were pretreated with curcumol and then exposed to TNF-α. Cell viability was analyzed using CCK-8, and the messenger ribonucleic acid and protein levels of inflammatory cytokines and PI3K/Akt/NF-κB-related signaling molecules were detected using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. The mouse IVDD model was established by puncturing the C6/7 level of the caudal spine, and then it was treated with curcumol after surgery. Alcian blue/orange G staining was performed to evaluate the severity of intervertebral disk damage, and immunohistochemistry was performed to detect the expression of TNF-α. Toxicologic effects of curcumol were measured by performing hematoxylin-eosin staining and enzyme-linked immunosorbent assay. 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 toxicologic 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.