Isovitexin alleviates fracture-related infection, promotes osteogenesis, and inhibits NF-κB pathway in rats

Fracture-related infection (FRI) represents a significant challenge in orthopedic care, often leading to prolonged inflammation, compromised bone healing, and substantial patient morbidity. Current treatment strategies primarily focus on infection eradication, but often fall short in simultaneously addressing the persistent inflammatory response and promoting robust bone regeneration. This dual problem necessitates novel therapeutic approaches that can both combat infection-driven inflammation and actively support the osteogenic process. Isovitexin, a naturally occurring flavonoid, is known for its anti-inflammatory properties, making it a compelling candidate to investigate for its potential to address these critical gaps in FRI management.

Researchers established a rat fracture infection model to evaluate isovitexin's effects, dividing animals into four groups: control, model (untreated infection), Vancomycin (standard antibiotic), and isovitexin. Bone healing was assessed through tissue staining, providing histological insights into callus formation and tissue integrity. Inflammatory factors and bone metabolism indicators were quantified using enzyme-linked immunosorbent assay (ELISA) and biochemical kits. The expression levels of key osteogenesis-related proteins and components of the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway were meticulously examined via Western blot analysis to elucidate underlying mechanisms.

Isovitexin treatment demonstrated superior efficacy compared to the model group, and notably, also outperformed the Vancomycin group in several key aspects. It significantly reduced inflammatory cell infiltration within bone tissue, indicating a potent anti-inflammatory effect. Furthermore, isovitexin actively promoted callus formation, a crucial step in bone repair, suggesting a pro-osteogenic role. The compound also effectively rebalanced bone metabolism, which is often disrupted during infection. This was evidenced by increased expression of osteogenesis-related proteins: Bone Morphogenetic Protein 2 (BMP2), Osteopontin (OPN), and Runt-related Transcription Factor 2 (RUNX2). Inflammatory cytokine profiles were also positively modulated: isovitexin decreased levels of pro-inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6, while simultaneously increasing the anti-inflammatory factor IL-10. Mechanistic investigations confirmed that isovitexin significantly inhibited the activation of the NF-κB signaling pathway, a central regulator of inflammation and immune responses. This inhibition likely underlies many of its observed beneficial effects. > Isovitexin treatment more effectively reduced inflammatory cell infiltration in bone tissue and promoted callus formation than the Vancomycin group.