Isopsoralen Promotes Mandibular Fracture Healing by Regulating Autophagy

BACKGROUND Mandibular fractures account for 40% to 65% of maxillofacial injuries, with about 10% developing delayed union or nonunion. Isopsoralen (ISO), a main active component of Psoralea corylifolia L., exhibits osteogenic and anti-inflammatory effects. However, the role of autophagy in ISO‑promoted mandibular fracture healing remains unclear. This study aimed to investigate the effects of ISO on mandibular fracture healing in rats and its underlying autophagy‑mediated mechanism. MATERIAL AND METHODS Specific pathogen-free-grade rats with left mandibular fractures were randomly assigned to 4 groups: normal saline (NS), ISO, 3‑methyladenine (3‑MA), and ISO+3‑MA. Interventions were given every 2 days. Fracture healing was assessed at 2, 4, and 6 weeks using the Lane‑Sandhu radiographic scoring system, micro-computed tomography, hematoxylin-eosin staining, enzyme-linked immunosorbent assay, and western blotting. RESULTS Compared with other groups, the 3‑MA group showed impaired healing, with lower radiographic scores, bone volume/total volume, bone mineral density, and trabecular number; higher trabecular separation; and sparse bone formation (all P<0.05). Relative to the NS group, the ISO group exhibited improved bone microarchitecture, elevated serum alkaline phosphatase and osteocalcin levels, and distinct autophagy marker changes (at 2 weeks: upregulated sequestosome 1 (P62), downregulated microtubule-associated protein 1 light chain 3 II/I (LC3-II/I); at 6 weeks: downregulated P62, Beclin-1, and LC3II/I; all P<0.05). Autophagy indices in the ISO+3‑MA group were comparable to those in the ISO group (P>0.05). CONCLUSIONS ISO stabilized autophagic flux and alleviated 3-MA-induced delayed mandibular fracture healing by regulating autophagy.