Green supported of silver nanoparticles on the surface of reduced graphene oxide: Investigation of its anti-epileptic activity on experimental models of epilepsy in mice

Abstract

This research demonstrated a novel, simple and environmentally safe process for the fabrication of graphene/silver composite using Malva sylvestris flower extract as a capping and reducing agent. Initially, the Malva sylvestris flower was used to make modified reduced graphene oxide that was coated by extract. The phytochemical groups of extract that have poylphenolic function can act as the green reducing agent for capping and reducing Ag ions on the surface of rGO (Reduced Graphene Oxide) to make the desired rGO/M.S./Ag NPs nanocomposite. The FT-IR, TEM, FE-SEM-EDX and XRD results confirmed the successful fabrication of the desired nanocomposite. The efficacy of the rGO/M.S./Ag NPs was first tested using the 6-Hz-induced seizure model. Subsequently, its effectiveness was assessed against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Additionally, the impact of the potent rGO/M.S./Ag NPs nanocomposite on Gamma amino butyric acid (GABA) levels in the brain was investigated to elucidate its potential mechanism of action. Furthermore, the effective rGO/M.S./Ag NPs nanocomposite underwent an actophotometer test to evaluate its potential to induce deficits in locomotor activity. During the 6-Hz seizure test, the rGO/M.S./Ag NPs nanocomposite demonstrated a significant and dose-dependent reduction in 6-Hz-induced seizures at doses of 30 and 90 µg/kg. Subsequently, the rGO/M.S./Ag NPs nanocomposite was assessed in MES and PTZ models. Interestingly, rGO/M.S./Ag NPs provided substantial and dose-dependent protection against MES (P < 0.01) and PTZ-induced (P < 0.01) seizures in mice. The rGO/M.S./Ag NPs nanocomposite exhibited a notable increase in brain GABA levels (P < 0.01) compared to the control, while showing no significant change in locomotor activity across all tested doses. Notably, a higher dose of rGO/M.S./Ag NPs nanocomposite (90 µg/kg, p.o.) and Diazepam (5 mg/mg, p.o.) completely prevented convulsions in all anticonvulsant tests. These results indicate that the rGO/M.S./Ag NPs nanocomposite possesses significant anticonvulsant properties, with one potential mechanism being the enhancement of GABA levels in the brain.