- Kojic acid in nanostructured lipid carriers significantly reduces brain oedema and improves neurological, motor, and memory outcomes after transient MCAO in male rats.
- KA-NLC increases anti-inflammatory IL-10 and modulates TNF-α, indicating inflammation reduction as a key protective mechanism.
- Neuroprotective efficacy is dose dependent: low and medium KA-NLC effective, high KA-NLC and low free KA ineffective; medium and high free KA beneficial.
Animal Model Exp Med. 2026 Sep 1. doi: 10.1002/ame2.70285. Online ahead of print.
ABSTRACT
BACKGROUND: Ischemic stroke triggers neuroinflammation and oxidative stress, leading to neuronal damage. Kojic acid (KA) has exhibited neuroprotective properties in other neurological pathologies but suffers from poor bioavailability. This study investigated whether KA encapsulated in nanostructured lipid carriers (KA-NLC) exerts protective effects against cerebral ischemia.
METHODS: Eighty adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) or control procedures and allocated into 10 experimental groups (n = 8 per group): intact, sham, MCAO, vehicle, three free-KA solution groups (10, 20, and 40 mg/kg), and three KA-NLC groups (1, 2, and 4 mg/kg). Functional outcomes were assessed using neurological scoring and Rota-Rod, Morris water maze, and shuttle box tests. Brain water content, hippocampal histology, and cerebrospinal fluid cytokine levels (interleukin-10 [IL-10], tumor necrosis factor-α [TNF-α]) were also evaluated.
RESULTS: Treatment with low and medium doses of KA-NLC and medium and high doses of free KA significantly reduced brain edema and improved neurological scores, motor coordination, and memory performance compared to the MCAO group. These functional improvements were associated with a significant increase in anti-inflammatory IL-10 and a modulation of TNF-α. Histological examination confirmed neuroprotection, with KA-NLC preserving hippocampal CA1 neural integrity. The high dose of KA-NLC and the low dose of free KA however were ineffective.
CONCLUSIONS: Nanoformulated KA confers significant neuroprotection against ischemic stroke by reducing edema, modulating inflammation, and preserving neuronal integrity, presenting a promising therapeutic strategy.
PMID:42678138 | DOI:10.1002/ame2.70285
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