AUTHOR=Alam Mohammad Zubair , Bagabir Hala Abubaker , Zaher Mohammad Alameen Faisal , Alqurashi Thamer M. A. , Alghamdi Badrah S. , Kazi Mohsin , Suhail Mohd , Alshahrany Gadah Ali , Alzahrani Noor Ahmed , Bakhalgi Rafal Mohammed , Al-Thepyani Mona , AboTaleb Hanin Abdulbaset , Aldhahri Rahaf Saeed , Juweiriya  , Tash Reham , Ashraf Ghulam Md 

TITLE=Curcumin-piperine nanoparticles mitigate cuprizone-induced cognitive impairment via antioxidant and anti-inflammatory mechanisms

JOURNAL=Frontiers in Nutrition

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1633855

DOI=10.3389/fnut.2025.1633855

ISSN=2296-861X

ABSTRACT=ObjectiveNeuroinflammation 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.MethodsSeventy-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.ResultsCuprizone 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 defenses 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.ConclusionThese 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.