Polyphenol Alleviation of Aluminum Chloride-Induced Cognitive Impairment and Synaptosomal Ca²⁺ Homeostasis in Rats

Authors

Muratova M.X.

Nаtiоnаl Univеrsitу оf Uzbеkistаn named after M. Ulugbek, Tashkent, Almazar 100174, Uzbekistan
Yuldasheva G.K.

Nаtiоnаl Univеrsitу оf Uzbеkistаn named after M. Ulugbek, Tashkent, Almazar 100174, Uzbekistan
Holiqova M.A.

Nаtiоnаl Univеrsitу оf Uzbеkistаn named after M. Ulugbek, Tashkent, Almazar 100174, Uzbekistan
Kоzоkоv I. B.

Institute of Biophysics and Biochemistry at the National University of Uzbekistan, 100174, Tashkent, Uzbekistan
Khоshimоv N.N.

Institute of Biophysics and Biochemistry at the National University of Uzbekistan, 100174, Tashkent, Uzbekistan
Erkinov I. O.

Impuls Medical Institute, 160114, Namangan, Uzbekistan
Kosimova Z.T.

Nаmаngаn Stаtе Univеrsitу. Namangan region, Namangan, 160119, Uzbekistan
Turaxanov I.N.

Tashkent state medical university Chirchik branch, 111709, Chirchik, Uzbekistan
Rakhimov R.N.

Institute of Bioorganic Chemistry, 100125, Tashkent, Uzbekistan

DOI:

https://doi.org/10.37547/ajbspi/Volume06Issue03-08

Keywords:

Aluminum chloride Alzheimer-like model polyphenol

Abstract

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].

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