Curcumin-piperine Therapy EnhancesNeuroprotection in the Brainstemof a Cuprizone-induced MultipleSclerosis Model

Abstract

Introduction: Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized
by neuroinflammation, oxidative stress, and demyelination. The cuprizone (CPZ) model is widely used to study
these pathological mechanisms. This study aimed to evaluate the neurotoxic effects of CPZ on the brainstem
and investigate the neuroprotective efficacy of curcumin and piperine nanoformulations prepared in black seed
oil. Materials and Methods: Seventy-five male Swiss albino mice were assigned to five groups: Control, CPZ,
CPZ with blank formulation, CPZ with curcumin formulation, and CPZ with curcumin-piperine formulation.
Mice received CPZ for 5 weeks to induce demyelination, followed by 2 weeks of treatment. Biochemical
analyses assessed oxidative stress markers (catalase, superoxide dismutase [SOD], malondialdehyde [MDA]),
inflammatory markers (tumor necrosis factor-alpha, interferon-gamma, glial fibrillary acidic protein, macrophage
inflammatory protein-1, C-C motif chemokine ligand-5), and myelin integrity (myelin basic protein [MBP]).
Results: Results showed that CPZ significantly decreased antioxidant enzyme activity, increased MDA levels,
and elevated inflammatory markers. Treatment with curcumin-piperine nanoformulation significantly restored
catalase and SOD activity, reduced MDA and inflammatory markers, and improved MBP levels, suggesting
enhanced remyelination. Discussion: The curcumin-piperine combination demonstrated superior neuroprotective
and anti-inflammatory effects compared to curcumin alone. Conclusion: These findings highlight the potential of
curcumin-piperine nanoformulations in mitigating MS-related neurodegeneration and suggest their promise for
future therapeutic applications.