Low-dose curcumin inhibits ferroptosis in human periodontal ligament stem cells via ROCK1 downregulation

Background Periodontitis is pathologically characterized by impaired function of human periodontal ligament stem cells (hPDLSCs). Curcumin has attracted considerable attention due to its anti-inflammatory and antioxidant properties; however, its effects on ferroptosis in hPDLSCs and the underlying mechanisms remain unclear. This study aimed to investigate the role of curcumin in hPDLSC ferroptosis and its potential regulatory mechanisms. Methods Following curcumin treatment at various concentrations, cell proliferation was assessed by CCK-8 assay, ROCK1 expression was detected by real-time quantitative PCR (RT-qPCR) and Western blotting, ferrous iron (Fe 2+ ) and glutathione (GSH) levels were measured using enzyme-linked immunosorbent assay kits, and mitochondrial membrane potential was evaluated by JC-1 staining. Results Low-dose curcumin (0.001–0.01 μM) significantly promoted hPDLSC proliferation, reduced intracellular Fe 2+ levels, elevated GSH content, suppressed the aberrant expression of ferroptosis-related proteins, and restored mitochondrial membrane potential. Notably, ROCK1 overexpression effectively reversed these protective effects, indicating that the action of curcumin is ROCK1-dependent. Furthermore, under Erastin-induced ferroptotic stress, low-dose curcumin reversed the Erastin-induced increases in Fe 2+ , ACSL4, and lipid peroxidation, restored GSH, Ferritin, and GPX4 levels, and rescued hPDLSC proliferation, with effects comparable to those of Ferrostatin-1. Conclusion Low-dose curcumin exerts cytoprotective effects on hPDLSCs by simultaneously promoting proliferation and suppressing ferroptosis via downregulation of ROCK1 expression. These findings unveil a novel mechanism by which curcumin modulates hPDLSC fate, provide a theoretical basis for hPDLSC-based protective strategies in periodontitis therapy, and highlight ROCK1 as a potential molecular target for periodontal regenerative intervention.