Modulation of S100β and Inflammatory Signalling by Isorhamnetin Enhances Peripheral Nerve Regeneration

Peripheral nerve injury is a leading cause of disability, which can result in partial or complete loss of motor, sensory, and autonomic function, and currently, there is no effective treatment for this incapacitating condition. It is important to identify new compounds that enable rapid and complete functional recovery. This study evaluated the effects of isorhamnetin (ISO) on functional rehabilitation in a mouse model of sciatic nerve injury. A total of 30 BALB/c mice, aged 8-10 weeks, were randomly assigned to three groups: sham, control, and treatment (n = 10/group). The mice in the ISO and Ctrl groups were operated on, whilst the animals in the sham group had their sciatic nerves exposed but left intact without crushing. The Ctrl and Sham groups received DMSO and normal saline intraperitoneally in equal volumes. In contrast, the ISO-treated group received ISO (10 mg/kg) dissolved in DMSO intraperitoneally from the day of nerve crush until the end of the study. All groups were fed regular chow and provided with sufficient water throughout the experiment. Behavioural analyses evaluated sensorimotor function recovery. Biochemical and haematological assays quantified oxidative stress markers and total blood count, while morphometric analysis determined structural recovery of muscle fibers. Nerve regeneration was indirectly evaluated by analyzing S100β protein levels and proinflammatory cytokines (IL-6 and TNF-α) expression. In the mouse model, ISO treatment resulted in substantial improvement in sensorimotor function recovery (p < 0.001). A substantial difference (p < 0.001) in blood glucose levels and oxidative stress markers was observed among all groups. The treated group displayed a remarkable improvement in the cross-sectional area of muscle fibers. At the end of the study, it was noted that ISO treatment significantly downregulated the expression of S100β, TNF-α, and IL-6, suggesting a positive impact of ISO on nerve regeneration. These findings indicate that ISO expedites the restoration of sensorimotor function following sciatic nerve injury by modulating S100β and proinflammatory cytokine expression and improving oxidative stress.