Abstract

ABSTRACT Chronic use of sertraline (SRT) for depression treatment can elevate oxidative stress, potentially leading to neuropathy. Cyperus esculentus extract (CEE) has demonstrated neuroprotective properties against oxidative imbalance, memory impairment, and neural degeneration. Adult male albino rats (40 rats) were placed into four groups: control (GI), CEE (200 mg/kg/day, orally) (GII), SRT (20 mg/kg/day, intraperitoneal) (GIII), and SRT+CEE (GIV). The rats’ spatial learning was assessed using a multiple T-maze after four weeks. Subsequently, rats were euthanized, and brain tissue samples were collected to assess oxidative stress indicators, monoamine oxidase, and dopamine. Brain tissue samples were also examined histologically and immunohistochemically for synaptophysin. SRT significantly increased monoamine oxidase activity, leading to oxidative stress, reduced dopamine levels, and neuronal degeneration in the brain. Treatment with SRT resulted in a decrease in the expression of synaptophysin in the cerebral cortex, dentate gyrus of the hippocampus, and cornu ammonis. These changes, in turn, led to impaired spatial learning. Co-treatment with CEE ameliorated changes in the levels of monoamine oxidase, dopamine, and synaptophysin, restored the redox balance, and improved spatial learning. CEE demonstrated a protective effect against sertraline-induced oxidative damage, preserving neurons, synaptogenesis, and spatial learning. These findings suggest CEE’s potential positive impact on sertraline-related neurodegeneration.

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