Neuroprotective effect of Azadirachta indica standardized extract in partial sciatic nerve injury in rats: Evidence from anti-inflammatory, antioxidant and anti-apoptotic studies

Chronic neuropathic pain is a common and widely recognized pain syndrome for patients and difficult to manage for physicians. Azadirachta indica (AI) possesses analgesic, anti-inflammatory, and antioxidant properties. To evaluate the neuroprotective effect of AI standardized extract in an animal model of peripheral neuropathy induced by partial sciatic nerve ligation (PSNL). PSNL was induced in male Wistar rats (180-200 g) with tight ligation of the nerve. Rats received treatment with either vehicle i.e. distilled water (PSNL control), Pyridoxine (100 mg/kg, p.o.) or AI (100, 200 and 400 mg/kg, p.o.) for 28 days. Various behavioral parameters, biochemical, molecular and histological parameters were evaluated. PSNL resulted in a significant decrease (p < 0.05) in allodynia, hyperalgesia, motor coordination and motor nerve conduction velocity (MNCV) whereas chronic treatment with AI (200 and 400 mg/kg) significantly attenuated (p < 0.05) these behavioral changes. Enhanced activity of oxidative-nitrosative stress, inflammatory mediators (TNF-α, IL-1β, and NF-κB) as well as mRNA expression of Bax, Caspase-3, and iNOs were significantly attenuated (p < 0.05) by AI treatment. It also significantly increased (p < 0.05) peripheral blood oxygen content and Bcl-2 mRNA expression. The flow cytometric analysis revealed that AI (200 and 400 mg/kg) treatment significantly attenuated neural apoptosis and reactive oxygen species levels. PSNL induced histological aberrations were also decreased by AI treatment. Azadirachta indica exerts its neuroprotection against PSNL induced neuropathic pain via inhibition of oxidative-nitrosative stress, the release of pro-inflammatory cytokines and apoptosis to improve MNCV (graphical abstract, Figure 1(Fig. 1)).