Mechanisms Underlying the Cognitive Benefits of Solanum macrocarpon Leaf n-Butanol Extract: Acetylcholinesterase Inhibition and Oxidative Stress Modulation

This study investigates the neuroprotective and anxiolytic effects of <i>Solanum macrocarpon</i> L. leaf n-butanol extract (SMB) in a zebrafish model of scopolamine (SCOP; 100 μM)-induced cognitive and behavioral impairments. SCOP, a muscarinic receptor antagonist, is commonly used to mimic memory deficits and anxiety-like behaviors associated with neurodegenerative conditions. Zebrafish were chronically exposed to SMB at concentrations of 1, 3, and 6 mg/L. Behavioral assessments included anxiety-related paradigms, such as novel tank diving (NTT), novel approach (NA), and light-dark transition (LD) tests, as well as cognitive assays, including the Y-maze and novel object recognition (NOR) tests. SMB significantly mitigated SCOP-induced anxiety-like behaviors and cognitive deficits in a dose-dependent manner. Biochemical analyses demonstrated that SMB inhibited acetylcholinesterase (AChE) overactivity, indicating restoration of cholinergic function. Furthermore, SMB enhanced the activity of endogenous antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) and significantly reduced oxidative stress biomarkers, including malondialdehyde (MDA) and protein carbonyls. These findings suggest that SMB may exert neuroprotective effects through modulation of cholinergic signaling and oxidative stress. Overall, SMB represents a promising phytotherapeutic candidate for mitigating cognitive and anxiety-related symptoms linked to oxidative damage. Further investigations are warranted to characterize its active constituents and assess long-term efficacy and safety in models of neurodegeneration.