Gamma-oryzanol alleviates intervertebral disc degeneration development by intercepting the IL-1β/NLRP3 inflammasome positive cycle.

Background: Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1β/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown.

Purpose: This study aims to validate the role of Ory in IVDD and explore the potential mechanism.

Study Design: Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory.

Method: The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1β-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels.

Results: Ory treatment inhibited IL-1β-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1β/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development.

Conclusion: Our results support the potential application of Ory as a therapeutic compound for IVDD.