Targeting Neurotoxicity and Inflammation in the Cerebral Cortex with Curcumin-Piperine Synergy

Mohammad Zubair Alam, Badrah Saeed Alghamdi, Athanasios Alexiou

Abstract


Background: Neuroinflammation, oxidative stress, and demyelination are central features of multiple sclerosis and related neurodegenerative disorders. Cuprizone (CPZ) is widely used to reproduce these pathological changes, inducing profound biochemical and structural alterations in the brain. This study investigated the impact of CPZ-induced neurotoxicity on key antioxidant, inflammatory, cholinergic, and myelin-related markers, and evaluated the therapeutic efficacy of curcumin- and piperine-based nanoformulations designed to enhance neuroprotection and repair.

Method: Male mice received CPZ to induce demyelination and associated oxidative and inflammatory stress. Animals were subsequently treated with a blank nanoformulation (BFZ), curcumin nanoformulation (CFZ), or a combined curcumin–piperine nanoformulation (PFZ). Biochemical analyses quantified antioxidant enzymes (catalase, superoxide dismutase), inflammatory mediators (COX-2, NF-κB-p65), cholinergic activity (acetylcholinesterase), neuroplasticity markers (CREB, NGF), and myelin basic protein (MBP) levels in the cerebral cortex.

Results: CPZ exposure led to marked oxidative stress, neuroinflammation, and neurodegeneration, reflected by decreased antioxidant enzyme levels, elevated COX-2 and NF-κB-p65, impaired cholinergic function, reduced MBP, and suppressed CREB. NGF expression increased significantly in the CPZ group as a compensatory response to neuronal injury. Nanoformulation treatments mitigated these pathological changes, with PFZ demonstrating the strongest therapeutic effect. PFZ restored antioxidant defences, reduced inflammatory markers, enhanced AChE activity, promoted remyelination, and improved CREB expression. PFZ also normalized NGF levels. Across all parameters, PFZ outperformed CFZ and BFZ, highlighting the role of piperine in enhancing curcumin bioavailability.

Conclusion: PFZ exerted potent neuroprotective and reparative effects against CPZ-induced neurotoxicity. These findings emphasize the value of optimized nanoformulations in strengthening phytochemical-based therapies for neurodegenerative diseases.

Keywords: Curcumin; Piperine; Nanoformulations; Neurodegeneration; Neuroinflammation; Oxidative stress


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References


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DOI: http://dx.doi.org/10.62940/als.v12i4.3775

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