Reversal of Aluminium chloride induced neurobehavioral deficit by Selenium: Involving NLRP3 inflammasome and cholinergic innervation Neuroprotective Effect of Selenium through NLRP3 Pathway
Iranian Journal of Pharmaceutical Sciences,
Vol. 21 No. 1 (2025),
21 January 2025
,
Page 344-356
https://doi.org/10.22037/ijps.v21i1.47768
Abstract
This study examines the efficacy of selenium as a therapeutic agent for reversing neurobehavioral deficits. A docking analysis was conducted to elucidate the interaction between selenium and the NLRP3 inflammasome residue. The research involved synthesizing and validating selenium nanoparticles within a controlled experimental design that employed Aluminium chloride (AlCl3) to induce neurotoxicity, followed by comprehensive neurobehavioral evaluations in Wistar rats. The results revealed that a one-month oral selenium administration led to significant enhancements in cognitive and motor functions, reduced proinflammatory cytokine levels, and decreased β-amyloid aggregation within the brain. Quantitative findings demonstrated that selenium treatment led to a marked enhancement in locomotor activity (from 54.83±0.60 to 60.5±0.76 counts, p<0.0001), improved performance within the radial arm maze (with baited arm entries rising from 9.83±0.58 to 16.5±0.43, p<0.0001). They augmented the recognition index in the novel object recognition assessment (from 33.77±0.74% to 61.38±1.10%, p<0.0001). On a biochemical level, selenium was found to decrease malondialdehyde concentrations and elevate antioxidant enzyme levels (SOD, CAT, GSH, p<0.01) while also significantly reducing levels of β-amyloid and TNF-α in the brain tissue. Additionally, selenium exhibited neuroprotective properties through both antioxidant mechanisms and cholinesterase pathways, thereby establishing it as a promising candidate for treating neurobehavioral deficits and neuroinflammation.
- AlCl3
- Docking study
- Neurobehavioral
- NLRP3
- Selenium
How to Cite
References
Mesulam M, et al. Nosology of Primary Progressive Aphasia and the Neuropathology of Language. Advances in experimental medicine and biology (2021) Vol. 1281:33-49.
Zeb Z, Sharif A, Akhtar B and Shahnaz. 3-Acetyl coumarin alleviate neuroinflammatory responses and oxidative stress in aluminum chloride-induced Alzheimer’s disease rat model. Inflammopharmacology (2024) Vol. 32(2):1371–86.
Chen ZR, Huang JB, Yang SL and Hong FF. Role of Cholinergic Signaling in Alzheimer’s Disease. Molecules (2022) Vol. 27(6):1816.
Gao X, Zhang X, Sun Y and Dai X. Mechanism of NLRP3 inflammasome activation and its role in Alzheimer’s disease. Explor Immunol (2022) Vol. 2:229–44.
Chen X, Zhang M, Ahmed M, Surapaneni KM, Veeraraghavan VP and Arulselvan P. Neuroprotective effects of onion against the aluminum chloride-induced Alzheimer’s disease in rats. Saudi Journal of Biological Sciences (2021) Vol. 28(8): 4232-4239.
Ahmed M, et al. Role of NLRP3 inflammasome in nanoparticle adjuvant-mediated immune response. Biomaterials Science (2025).
Zhang Y, et al. Role of Selenoproteins in Redox Regulation of Signaling and the Antioxidant System. Antioxidants (2020) Vol. 9(5):383.
Velankar S, Burley SK, Kurisu G, Hoch JC and Markley JL. The Protein Data Bank Archive. Methods Mol Biol (2021) Vol. 2305:3-21.
Eberhardt J, Santos-Martins D, Tillack AF and Forli S. AutoDock Vina 1.2.0: new docking methods, expanded force field, and Python bindings. Journal of Chemical Information and Modelling (2021) Vol. 61(8): 3891–3898.
Gayathiri E, et al. Multitargeted pharmacokinetics, molecular docking and network pharmacology-based identification of effective phytocompounds from Sauropus androgynus (L.) for inflammation and cancer treatment. Journal of Biomolecular Structure and Dynamics (2023) Vol. 1–14.
Blinov AV, Maglakelidze DG, Brazhko EA, Blinova AA, Gvozdenko AA and Pirogov MA. Optimization of the Technique for Obtaining Selenium Nanoparticles Stabilized with Cocamidopropyl Betaine. Russian Journal of General Chemistry (2022) Vol. 92(12): 2939–2943.
Sutar GV., Sajane SJ, Taralekar ST, Nargatti PI and Jadhav AA. Evaluation of cns stimulating activity of hydroalcoholic extract of Brassica oleracea L. var. italica in laboratory animals. Annals of Phytomedicine: An International Journal (2021) Vol. 10(2).
Boiangiu RS, et al. Cognitive Facilitation and Antioxidant Effects of an Essential Oil Mix on Scopolamine-Induced Amnesia in Rats: Molecular Modeling of In Vitro and In Vivo Approaches. Molecules (2020) Vol. 25(7):1519.
Rossato JI, et al. NMDARs control object recognition memory destabilization and reconsolidation. Brain Res Bull (2023) Vol. 197:42–8.
Kale M, Kolhe S and Tembhurne S. Neuroprotective effect of Sesbania sesban on Scopolamine induced amnesia in wistar rats: Behavioral and biochemical study. Asian Journal of Pharmacy and Pharmacology (2018) Vol. 4(5): 657–661.
Kazmi I, Al-Abbasi FA, Afzal M, Shahid Nadeem M and Altayb HN. Sterubin protects against chemically-induced Alzheimer’s disease by reducing biomarkers of inflammation- IL-6/ IL-β/ TNF-α and oxidative stress- SOD/MDA in rats. Saudi J Biol Sci (2023) Vol. 30(2):103560.
Gordón Pidal JM, et al. Micromotor-based electrochemical immunoassays for reliable determination of amyloid-β (1–42) in Alzheimer’s diagnosed clinical samples. Biosensors & Bioelectronics (2024) Vol. 249, 115988.
Hira K and Sajeli BA. Methods for Evaluation of TNF-α Inhibition Effect. Methods Mol Biol (2021) Vol. 2248:271-279.
Maurya R, Sharma A and Naqvi S. Decoding NLRP3 Inflammasome Activation in Alzheimer’s Disease: A Focus on Receptor Dynamics. Mol Neurobiol (2025) Vol. 15.
Jung ES, Suh K, Han J, Kim H, Kang HS, Choi WS and Mook-Jung I. Amyloid-β activates NLRP3 inflammasomes by affecting microglial immunometabolism through the Syk-AMPK pathway. Aging Cell (2022) Vol. 21(5): e13623.
Zhang Y, et al. Role of Selenoproteins in Redox Regulation of Signaling and the Antioxidant System: A Review. Antioxidants (2020) Vol. 9(5):383.
Abo zO, Aziza S, EL-sonbaty S, and Afifi M. Selenium nanoparticles coated with resveratrol ameliorates the neurobiochemical abnormalities by attenuating oxidative stress and improving neurotransmissions in AlCl3-Induced Alzheimer’s model of rats. Benha Veterinary Medical Journal (2021) Vol. 41(1): 173-177.
Di S, Yu M, Guan H and Zhou Y. Neuroprotective effect of Betalain against AlCl3-induced Alzheimer's disease in Sprague Dawley Rats via putative modulation of oxidative stress and nuclear factor kappa B (NF-κB) signaling pathway. Biomedicine & Pharmacotherapy (2021) Vol. 137, 11136.
Awad SM, et al. Efficacy of curcumin-selenium nanoemulsion in alleviating oxidative damage induced by aluminum chloride in a rat model of Alzheimer’s disease. J Mol Histol (2025) Vol. 56(2):122.
Oyagbemi AA, et al. Apigenin mitigates oxidative stress, neuroinflammation, and cognitive impairment but enhances learning and memory in aluminum chloride‐induced neurotoxicity in rats. Alzheimer’s & Dementia (2025) Vol. 21(5).
Attia FM, Kassab RB, Ahmed-Farid OA, Abdel Moneim AE and El-Yamany NA. Zinc Oxide Nanoparticles Attenuated Neurochemical and Histopathological Alterations Associated with Aluminium Chloride Intoxication in Rats. Biol Trace Elem Res (2025) Vol. 203(4):2058–71.
Zarneshan SN, et al. Polydatin attenuates Alzheimer’s disease induced by aluminum chloride in rats: evidence for its antioxidant and anti-inflammatory effects. Front Pharmacol (2025) Vol. 16.
Li D, Wang M. Shikonin Attenuate Behavioral Defects, Oxidative Stress, and Neuroinflammation During Aluminum Chloride-induced Alzheimer’s Disease Condition in an in vivo Experimental Model. Pharmacogn Mag (2024) Vol. 20(3):983–95.
- Abstract Viewed: 169 times
- IJPS_Volume21_Issue1_Pages344-356 Downloaded: 123 times