Scutellarein Attenuates Intervertebral Disc Degeneration by Promoting PINK1/Parkin-Mediated Mitophagy to Alleviate Inflammation, Ferroptosis, and Mitochondrial Dysfunction in Nucleus Pulposus Cells.

Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain and is driven by oxidative stress, inflammation, and ferroptosis. While mitophagy regulates ferroptosis in other diseases, its role in IVDD remains unclear. The potential of scutellarein, a flavonoid with antioxidant properties, to treat IVDD has not yet been explored. Primary human nucleus pulposus (HNP) cells were treated with tert-butyl hydroperoxide (TBHP) to establish an in vitro IVDD model. Mitophagy was inhibited by cyclosporin A (CsA) treatment. Radiographic and histopathological analyses were performed in a rodent IVDD model. Key markers (IL-1β, ACSL4, GPX4, PINK1, LC3, and PI3K/mTOR) were assessed. Scutellarein preserved the NPC phenotype, reduced inflammation, and suppressed ferroptosis by activating PINK1/Parkin-mediated mitophagy. It restored mitochondrial function and inhibited the PI3K/AKT/mTOR pathway. In vivo, scutellarein attenuated IVDD progression; downregulated the expression of IL-1β and ACSL4; and upregulated the expression of collagen II, GPX4, PINK1, and LC3. Scutellarein mitigates IVDD by inducing mitophagy to inhibit ferroptosis and restore mitochondrial function, highlighting its therapeutic potential.