Abstract

Global cerebral ischemia (GCI) leads to significant neuronal damage, particularly in the CA1 region of the hippocampus, resulting in memory deficits and neurodegeneration. This study investigates the neuroprotective effects of berberine (BBR) and menthol (ME) individually and in combination in a rat model of GCI. Fifty male Wistar rats were divided into five groups: Sham, GCI, GCI + BBR, GCI + ME, and GCI + BBR + ME. GCI was induced by occluding both common carotid arteries for 20 min. Treatments were administered intragastrically 5 min post-GCI induction. Stereological analyses, short-term spatial memory tests, and antioxidant enzyme activities were evaluated 24 h after GCI. Results showed that the Sham group had the highest stereological parameters and memory function, while the GCI group exhibited the most significant neuronal damage and impaired memory. Both BBR and ME treatments improved neuronal preservation and memory function compared to the GCI group, with the combination of BBR and ME showing a subadditive effect but no synergistic benefit. These findings confirm that BBR and ME have neuroprotective effects and enhance antioxidant responses but do not provide a synergistic advantage when combined. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2025.