Molecular Docking and Experimental Evaluation of Trolox and Neocuproine in Targeting Neuroinflammation in Neuropathic...

This study was carried out to evaluate the therapeutic efficacy of Neocuproine/Trolox treatment on chronic neuropathy induced by Chronic Constriction Injury (CCI). Rats (n = 40) were grouped as Sham, CCI, CCI+Trolox, and CCI+Neocuproine. Rats with proven neuropathy were given 80 mg/kg/day (i.p.) Trolox and 100 μM/day (i.p.) Neocuproine for 7 days. Open field and tail withdrawal tests were conducted at baseline and on days 7 and 14. ELISA test was employed in analyzing IL 1β, IL 10, TNF-α, and TGF-β levels in spinal cord and cortex tissues of rats. To explore potential mechanistic interactions, molecular docking was conducted with the key cytokine receptor. On day 14, a significant decrease in total path taken, number of frames entered, and delay values were observed in CCI group compared to the control, whereas significant increases were observed in total path taken, number of frames entered, and delay values in the CCI+Neocuproine/Trolox treatment groups compared to CCI group (p < 0.05 for all). Docking analyses were performed for Neocuproine/Trolox. In comparison to the sham group, IL‑1β and TNF-α levels in spinal cord and cortex tissues were higher, while IL‑10 and TGF-β levels were lower (p < 0.05). Neocuproine/Trolox treatments reduced proinflammatory cytokine levels and elevated anti-inflammatory cytokine levels in CCI rats on day 14 (p < 0.05 for all). Considering the docking score of Neocuproine/Trolox, high scores were observed, especially with TNF-α and TGF-β receptor. The results suggest that Neocuproine/Trolox treatments induce thermal anti-hyperalgesic behaviors in CCI-induced pain, showing significant improvements in locomotor activity, and achieve these by reducing the production of proinflammatory cytokines and elevating that of anti-inflammatory cytokines.