From anthelmintic to neurotherapeutic: exploring the regenerative potential of niclosamide in sciatic nerve injury.

Peripheral nerve injury (PNI) remains a major clinical challenge, often leading to chronic neuropathic pain and persistent motor and sensory dysfunction. Despite advances in microsurgical repair, effective pharmacological strategies to attenuate neuroinflammation and promote functional recovery are still lacking. Niclosamide, a well-known FDA-approved anthelmintic agent, has recently emerged as a potent modulator of multiple intracellular signaling pathways implicated in neuroinflammation. In the present study, we investigated the neuroprotective and anti-inflammatory effects of niclosamide in a rat model of sciatic nerve injury induced by double ligation. Adult male Wistar rats were assigned to five groups (sham, control, and niclosamide-treated groups at 2, 5, and 10 mg/kg, i.p.). Behavioral analyses using von Frey and hot plate tests revealed that niclosamide significantly reduced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. Histopathological evaluation showed markedly reduced perineural inflammation and cellular infiltration in niclosamide-treated rats. At the molecular level, ELISA demonstrated suppression of TNF-α and MCP-1, accompanied by increased IL-10 levels. Western blot analysis confirmed significant downregulation of NF-κB, TLR4, and NLRP3, alongside enhanced expression of BDNF, indicating both anti-inflammatory and neuroregenerative effects. Collectively, these findings highlight niclosamide as a promising multi-target therapeutic agent capable of mitigating neuroinflammatory signaling and enhancing peripheral nerve repair following injury.