Curcumin-Piperine Nanoparticles Mitigate Cuprizone-Induced Cognitive Impairment via Antioxidant and Anti-Inflammatory Mechanisms

Mohammad Zubair Alam^1*Hala Bagabir¹Mohammad Alameen Faisal Zaher¹Thamer M. A. Alqurashi¹Badrah Saeed Alghamdi¹Mohsin Kazi²Ghulam Md Ashraf³Mohd Suhail¹Gadah Ali Alshahrany¹Noor Ahmed Alzahrani¹Rafal Mohammed Bakhalgi¹Mona Al-Thepyani¹Hanin Abdulbaset Abotaleb¹Rahaf Saeed Aldhahri¹Juweiriya Juweiriya¹Reham Tash¹

• ¹King Abdulaziz University, Jeddah, Saudi Arabia
• ²King Saud University, Riyadh, Saudi Arabia
• ³Xi'an Jiaotong-Liverpool University, Suzhou, China

Objective: Neuroinflammation is a key contributor to many neurodegenerative diseases. Cuprizone, a copper-chelating agent, is widely used in research to induce neurotoxicity and demyelination, mimicking the pathology of multiple sclerosis. This study investigates the protective and therapeutic effects of curcumin and piperine nanoformulations prepared in Zanthoxylum rhetsa seed oil against cuprizone-induced neurotoxicity in mice. Methods: Seventy-five Swiss albino mice were divided into five groups: control, cuprizone-treated, blank formulation-treated, curcumin-treated, and curcumin with piperine-treated groups. Behavioral assessments, along with biochemical and histological analyses of the hippocampus, were conducted to evaluate learning and memory, antioxidant enzyme activity, neuroinflammatory markers, and cellular integrity. Results: Cuprizone exposure significantly impaired cognitive function and induced oxidative stress, as evidenced by decreased levels of key antioxidant enzymes like catalase, superoxide dismutase, glutathione and glutathione peroxidases. Additionally, increased levels of neuroinflammatory markers such as GFAP, MCP-1, MIP-1, and CCL-5 were observed. Treatment with curcumin and piperine nanoformulations mitigated these effects by restoring antioxidant defences and modulating inflammatory responses. The curcumin-piperine combination exhibited superior neuroprotection compared to curcumin alone, enhancing memory performance and reducing neuroinflammation more effectively. The results highlight the potential of curcumin and piperine nanoformulations in alleviating neurotoxicity and cognitive impairments associated with neurodegenerative disorders. Conclusion: These findings suggest that curcumin-based nanoformulations could serve as promising therapeutic agents for treating neuroinflammatory diseases, warranting further studies to explore their precise mechanisms and optimize their clinical applications.