Background: Alzheimer’s disease (AD) is driven by convergent mechanisms that include oxidative stress and Ca²⁺-dependent synaptic failure [1–4]. Aluminum chloride (AlCl₃) exposure is frequently used to reproduce selected AD‑like features in rodents, including cognitive/behavioral decline and redox imbalance [7–9]. Here, dissertation-derived experimental results are reformatted into an IMRAD manuscript to assess whether a plant-derived polyphenol fraction (G‑31) can correct AlCl₃‑evoked behavioral suppression and synaptosomal Ca²⁺ dysregulation.

Methods: Male white rats (180–200 g) were assigned to control and AlCl₃ model groups; AlCl₃ was administered (10 mg/kg, i.p., once daily, 7 days) to induce AD‑like neurotoxicity. G‑31 was given at 50 mg/kg using different delivery routes (i.p., intranasal, or per os; n=6/group). Behavior was quantified by open-field exploration (42‑square arena, 3 min) [5], Conditioned reflex passive avoidance (CRPA) and Conditioned reflex active avoidance (CRAA). Synaptosomes were prepared by differential centrifugation and loaded with Fluo‑4AM to quantify cytosolic Ca²⁺ kinetics (peak amplitude, AUC, τ) under Ca²⁺‑containing (2 mM CaCl₂) or Ca²⁺‑free (EGTA) conditions. Oxidative stress was evaluated by malondialdehyde (MDA) in blood and brain homogenates.

Results: The AlCl₃ model robustly increased lipid peroxidation: MDA rose from 11.4±0.1 to 30.2±0.3 μmol/mg tissue in blood and from 4.54±0.4 to 8.35±0.2 μmol/mg tissue in brain (p<0.05–0.01). AlCl₃ exposure also produced a hypomotor/exploratory phenotype in the open field and decreased performance in avoidance-based cognitive paradigms. At the synaptic level, synaptosomal Ca²⁺ transients deviated from the control pattern, consistent with Ca²⁺ dyshomeostasis—an established mechanistic hallmark of AD-related synaptic vulnerability [10–12]. Across regimens, G‑31 shifted behavioral and Ca²⁺ readouts toward the control profile; intranasal delivery produced the most pronounced behavioral correction in this dataset.

Conclusion: These results support a working model in which AlCl₃ triggers oxidative membrane injury and synaptosomal Ca²⁺ dysregulation that jointly contribute to cognitive suppression, and polyphenol G‑31 provides partial, multi-level correction—potentially via antioxidant/metal-chelating effects and normalization of Ca²⁺ entry/clearance mechanisms [14–19].

Aluminum chloride, Alzheimer-like model, polyphenol

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