Fargesin enhances the condition of intervertebral disc degeneration by suppressing BRD4 expression and influencing autophagy in NPCs.

Intervertebral Disc Degeneration (IVDD) stands as the prevalent chronic skeletal muscle degenerative disease and the primary culprit behind low back pain, yet its underlying mechanism remains elusive. Fargesin, a novel bioactive lignan compound known for its anti-inflammatory properties, also has an unclear mechanism of action in IVDD. To unravel this mechanism, we employed the CCK8 assay to determine the optimal treatment duration and concentration of Fargesin. For our in vitro experiments, we induced NPCs cells with IL-1β to mimic the IVDD model, while for in vivo studies, we established a rat IVDD model through surgical intervention coupled with an injection of 0.1mL IL-1β (1 µg/mL). We utilized Elisa to measure the levels of inflammatory cytokines IL-6 and TNF-α. Western blotting and immunofluorescence techniques were harnessed to assess the expression of autophagy markers and BRD4 protein in the cells. Additionally, X-ray imaging, HE staining, and safranin o-fast green aided in evaluating the intervertebral disc lesions in our in vitro experiments. Our findings revealed that Fargesin significantly suppressed the inflammatory response triggered by IL-1β in NPCs and attenuated the elevated expression of BRD4. By downregulating BRD4 expression, Fargesin upregulated the proteins LC3II/I, Beclin-1, and LAMP1 related to the autophagy signaling pathway, while decreasing P62 expression. Far activates the autophagy signaling pathway by inhibiting the expression of BRD4, enhances the activity of NPCs, and alleviates the pathological damage of intervertebral discs with ivdd lesions.