The Synergistic Effect of Curcumin and Piperine Nanoparticles on Methamphetamine-induced Neurotoxicity, Oxidative Stress, and Memory Impairments in Mice Brain

Background: Methamphetamine (METH) is a highly addictive neural stimulant that severely affects the CNS and can induce oxidative damage. Piperine and curcumin are active constituents that have numerous properties, including antioxidant, anti-inflammatory, and neuroprotective Objective: In this study, the synergistic effect of piperine and curcumin nanoparticles was investigated on the acute doses of METH-induced neurotoxicity in mice brains. Methods: METH (6 mg/kg, i.p) was administered to 14 groups of mice and piperine-curcumin nanoparticles at different doses (10, 20, 40 mg/kg and 20, 40 and 60 mg/kg, respectively) were administered. Open field test (OFT) and conditioned place preference (CPP) were used to investigate locomotor activity, anxiety-like behavior, and addictive behavior in mice. Oxidative stress biomarkers (reactive oxygen species (ROS), protein carbonyl content, lipid peroxidation, glutathione content, and mitochondrial function were evaluated in isolated brain mitochondria. Results: We found that piperine and curcumin nanoparticles significantly decreased hyperlocomotion and anxiety-like behavior in METH-treated mice. Also, METH enhanced CPP whilst piperine and curcumin nanoparticles suppressed the effect of METH-induced CPP. METH administration significantly increased ROS, protein carbonyl content, and lipid peroxidation and decreased glutathione content and mitochondrial function in the isolated brain mitochondria. Piperine and curcumin nanoparticles (at all doses) showed synergistic effects on reducing oxidative damages in a dosedependent manner compared to the METH group. Conclusion: In conclusion, combined piperine and curcumin nanoparticles showed greater neuroprotective effects against METH-induced neurotoxicity due to their greater permeability and better antioxidant properties than piperine and curcumin alone