Combating Neuroinflammation and Neurotoxicity with Curcumin-Piperine Nanoformulations

Background: Neuroinflammation plays a critical role in the progression of neurodegenerative diseases such as multiple sclerosis, Alzheimer's, and Parkinson's disease. The Cuprizone (CPZ)- induced model is widely used to study neuroinflammatory mechanisms, as it selectively targets oligodendrocytes, causing demyelination and oxidative stress. Objectives: This study investigates the neuroprotective effects of curcumin nanoformulations prepared in Zanthoxylum rhetsa seed oil against CPZ-induced neurotoxicity in Swiss albino mice. Materials and Methods: The study assessed antioxidative enzyme activities and inflammatory markers, including catalase, superoxide dismutase, glutathione peroxidase, GFAP, MCP-1, MIP-1, and CCL-5. Results: The results indicated that CPZ exposure significantly reduced catalase and SOD levels while increasing oxidative stress markers such as Malondialdehyde (MDA) and inflammatory cytokines. The administration of curcumin nanoformulations demonstrated substantial neuroprotection by restoring antioxidative enzyme levels, reducing inflammation, and mitigating myelin degradation. Notably, the combination of curcumin with Piperine (PFZ) exhibited the highest neuroprotective potential, as it significantly enhanced catalase and SOD activity while suppressing inflammatory markers like TNFα and GFAP. Furthermore, PFZ-treated mice displayed improved Myelin Basic Protein (MBP) levels, indicating enhanced remyelination. Conclusion: The findings suggest that curcumin-based nanoformulations, particularly those combined with piperine, hold promise as therapeutic strategies for mitigating neuroinflammation and oxidative damage associated with demyelination. These results provide valuable insights into the potential of plant-derived antioxidants in treating neurodegenerative conditions.