Abstract:
Introduction. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by
cognitive decline and oxidative stress. Natural bioactive compounds with antioxidant and
neuroprotective properties have gained interest as potential therapeutic agents. Solanum macrocarpon,
known for its antimicrobial, antioxidant, and anti-inflammatory effects, may offer neuroprotective
benefits. This study investigates the effects of its ethanolic extract (SMEE) in a zebrafish model of
scopolamine (Scop)-induced cognitive impairment, emphasizing its impact on oxidative stress,
cholinergic modulation, and behavioral parameters.
Materials and Methods. Zebrafish were exposed to SMEE at concentrations of 1, 3, and 6 mg/L for
23 days before immersion in scopolamine (100 μM) to induce cognitive deficits. Behavioral tests,
including the Novel Tank Diving Test (NTT), Novel Approach Test, Y-Maze, and Novel Object
Recognition (NOR), were performed to assess memory and anxiety-related behaviors.
Acetylcholinesterase (AChE) activity and oxidative stress markers were quantified using
spectrophotometric methods. To elucidate the neuroprotective mechanisms, antioxidant enzyme
activities (superoxide dismutase - SOD, catalase - CAT, and glutathione peroxidase - GPX) were
measured, along with markers of oxidative damage such as protein carbonylation and lipid
peroxidation (malondialdehyde - MDA). Pearson correlation analyses were conducted to assess
relationships between behavioral parameters, enzymatic activities, and oxidative stress markers. In
addition, HPLC analysis identified chlorogenic acid and rutin as major polyphenolic components in
SMEE, followed by an in silico pharmacokinetic evaluation (ADMET) to assess their absorption,
metabolism, and toxicity profiles.
Results. SMEE administration significantly improved spatial and recognition memory, reducing
anxiety-like behavior in zebrafish exposed to Scop. The extract also counteracted oxidative stress by
enhancing the activity of antioxidant enzymes (SOD, CAT, GPX) and reducing protein oxidation and
lipid peroxidation (MDA levels). Pearson correlation analysis showed significant negative correlations
between MDA levels and behavioral performance, as well as SOD, CAT, and GPX activities,
indicating a direct link between oxidative stress reduction and cognitive improvement. HPLC analysis
confirmed the presence of chlorogenic acid and rutin, which exhibited strong antioxidant properties.
ADMET analysis suggested that these compounds have lower intestinal absorption but a favorable
neuroprotective profile.
Conclusions. The findings indicate that Solanum macrocarpon ethanolic extract has potential
therapeutic benefits in mitigating cognitive decline and oxidative stress, supporting its use as a natural
neuroprotective agent in Alzheimer's disease. Further studies are warranted to elucidate its precise
mechanisms and clinical relevance.
