Neuroprotective effects of kojic acid and nano-kojic acid in experimental brain ischemia induced by bilateral common carotid artery occlusion

Articles in Press

Document Type : Original Article

Authors

1 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

2 Pharmaceutical Sciences Research Center, Institute of Herbal Medicines and Metabolic Disorders, Mazandaran University of Medical Sciences, Sari, Iran

3 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

4 Department of Anatomy, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

5 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

10.22038/ijbms.2025.89790.19367

Abstract

Objective(s): Brain ischemia remains a leading cause of death and neurological disability worldwide, with current treatments limited by narrow therapeutic windows and insufficient neuroprotection. Kojic acid (KA), a natural compound with demonstrated anti-oxidant and anti-inflammatory properties, has not been thoroughly evaluated in cerebral ischemia. Its limited brain bioavailability may have hindered the identification of its potential therapeutic effects. This study aimed to investigate the effects of both KA and its nanostructured lipid carriers (nKA) in a rat bilateral common carotid artery occlusion (BCCAO) model.
Materials and Methods: Adult male rats were randomly allocated to seven groups: sham, BCCAO, KA (1 and 10 mg/kg), nKA (1 and 10 mg/kg), and vehicle. Following BCCAO surgery, animals received intraperitoneal treatments for seven days. Behavioral assessments included the modified neurological severity score and grid walk test. Brain and serum samples were collected to evaluate histopathology, gene expression, oxidative stress markers, inflammatory cytokines, and pharmacokinetic parameters.
Results: Histological analysis indicated reduced neuronal loss in both KA and nKA-treated groups. Notably, only nKA significantly improved behavioral outcomes. Both treatments reduced the pro-apoptotic gene BAX and the pro-inflammatory cytokine TNF-α, while nKA additionally increased Nrf2 and reduced IL-6 expression. Both formulations mitigated oxidative stress by decreasing reactive oxygen species, protein carbonylation, and malondialdehyde levels, while also increasing glutathione concentrations.
Conclusion: Nano-kojic acid showed better neurobehavioral improvements, while both forms reduced oxidative stress and inflammation, indicating neuroprotective potential. Further studies are needed to clarify mechanisms and long-term safety.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

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Available Online from 29 October 2025

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