Agriculture and Biomedical
| Open Access |
DOI: Reduction of Platelet Hyperactivity by Polyphenol in An Experimental Model of Alzheimer's Disease in Rats
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 Muratova M.X. , 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 Rakhimov R.N. , Institute of Bioorganic Chemistry, 100125, Tashkent, Uzbekistan Abduganiyeva M.A. , Nizami National Pedagogical University of UzbekistanAbstract
Background: Alzheimer's disease (AD) is increasingly associated not only with neuronal degeneration but also with platelet dysfunction, altered hemostasis, and calcium-dependent peripheral signaling abnormalities. Objective: To evaluate the effects of G-40 polyphenol on platelet aggregation, coagulation hemostasis, and intracellular calcium mobilization in a rat AD-like condition. Methods: Platelet-rich plasma and platelet suspensions obtained from control rats and rats with an AlCl3-induced AD-like condition were analyzed. Platelet aggregation was assessed by Born aggregometry after stimulation with ADP, adrenaline, and collagen. Coagulation was evaluated using thrombin time (TT), activated partial thromboplastin time (APTT/QFTV), and prothrombin time (PT, TechPlastin). Intracellular calcium was monitored in Fluo-4 AM-loaded platelets after ADP stimulation, with EGTA used as a calcium-chelating control. G-40 was tested primarily at 50 uM, with concentration-response evaluation in the 10-100 uM range for calcium readouts. Results: The AD model displayed spontaneous platelet aggregation and enhanced agonist-induced aggregation relative to controls. G-40 partially inhibited ADP- and collagen-induced aggregation in both normal and AD conditions. The AD model shortened TT, APTT, and PT, indicating a procoagulant shift, whereas G-40 markedly prolonged all three parameters. G-40 also suppressed ADP-induced intracellular Ca2+ mobilization by 40-55%, with 50 uM showing the greatest effect. Conclusions: G-40 exerts a multi-target antiplatelet and anticoagulant action in the AD-like state. Its effects are most consistently explained by attenuation of Ca2+-dependent platelet activation together with interference at common coagulation pathway steps. These findings support G-40 as a promising candidate for correcting platelet hyperreactivity and hemostatic imbalance associated with AD.
Keywords
Alzheimer's disease, platelets, aggregation
References
Strickland S. Blood will out: vascular contributions to Alzheimer's disease. J Clin Invest. 2018;128(2):556-563.
Cortes-Canteli M, Strickland S. Fibrinogen and altered hemostasis in Alzheimer's disease. J Alzheimers Dis. 2012;32(3):599-608.
Ahn HJ, Zamolodchikov D, Cortes-Canteli M, Norris EH, Glickman JF, Strickland S. Alzheimer's disease peptide beta-amyloid interacts with fibrinogen and induces its oligomerization. Proc Natl Acad Sci U S A. 2010;107(50):21812-21817.
Zamolodchikov D, Renne T, Strickland S. The Alzheimer's disease peptide beta-amyloid promotes thrombin generation through activation of coagulation factor XII. J Thromb Haemost. 2016;14(5):995-1007.
Sevush S, Jy W, Horstman LL, Mao WW, Kolodny L, Ahn YS. Platelet activation in Alzheimer disease. Arch Neurol. 1998;55(4):530-536.
Burnouf T, Walker TL. The multifaceted role of platelets in mediating brain function. Blood. 2022;140(8):815-827.
Varga-Szabo D, Braun A, Nieswandt B. Calcium signaling in platelets. J Thromb Haemost. 2009;7(7):1057-1066.
Nignpense BE, Chinkwo KA, Blanchard CL, Santhakumar AB. Polyphenols: modulators of platelet function and platelet microparticle generation? Int J Mol Sci. 2019;21(1):146.
Bijak M, Sut A, Kosiorek A, Saluk-Bijak J, Golanski J. Dual anticoagulant/antiplatelet activity of polyphenolic grape seeds extract. Nutrients. 2019;11(1):93.
Marchelak A, Kolodziejczyk-Czepas J, Ponczek MB, et al. Flavonol- and A-type procyanidin-rich extracts of Prunus spinosa L. flower exhibit anticoagulant activity through direct thrombin inhibition, but do not affect platelet aggregation in vitro. Front Pharmacol. 2023;14:1307373.
Born GVR. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962;194:927-929.
Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985;260:3440-3450.
Petrischev NN, Vasina LV, Seliutin AV, et al. The application of Fluo-3 AM in measurement of level of cytoplasmic calcium in thrombocytes by flow cytofluorometry. Klin Lab Diagn. 2017;62(2):97-99.
Khan K, Emad NA, Sultana Y. Inducing agents for Alzheimer's disease in animal models. J Explor Res Pharmacol. 2024;9(3):169-179.
Dobrydneva Y, Williams RL, Blackmore PF. trans-Resveratrol inhibits calcium influx in thrombin-stimulated human platelets. Br J Pharmacol. 1999;128(1):149-157.
Ehrlich D, Hochstrasser T, Humpel C. Effects of oxidative stress on amyloid precursor protein processing in rat and human platelets. Platelets. 2013;24:26-36.
Donner L, Falker K, Gremer L, et al. Platelets contribute to amyloid-beta aggregation in cerebral vessels through integrin alphaIIbbeta3-induced outside-in signaling and clusterin release. Sci Signal. 2016;9:ra52.
Ripova D, Platilova V, Strunecka A, Jirak R, Hoschl C. Cytosolic calcium alterations in platelets of patients with early stages of Alzheimer's disease. Neurobiol Aging. 2000;21(5):729-734.
Khoshimov, N. N., Saidmurodov, S. A., & Rakhimov, R. N. (2021). The Mechanism of action of polyphenol on changes in the dynamics of calcium in the synaptosomes of the rat brain against the background of glutamate. The American journal of applied sciences, 3 (03), 48-55.
Mukhtorov, A. A., Mamadaminov, R. R., Khoshimov, N. N., Nasirov, K. E., Rakhimov, R. N., & Gaybullo, L. X. (2022). Regulation of transport of Ca2+ NMDA-receptors in rat brain synaptosomes under the influence of polyphenols. European Journal of Medicine, 10(1), 3-11.
Rakhimov, R. N., Khoshimov, N. N., Kurbanova, A. D., Komilov, K. U., Makhmanov, D. M., Kadirova, S. O., & Abdulladjanova, N. G. (2021). Isolation of new ellagitannins from plants of Euphorbiaceous and its effect on calcium transport in the nerve cell of the rat brain. Annals of the Romanian Society for Cell Biology, 25(6), 2758-2768.
Khoshimov, N. N., Rahimova, G. L., Mirzakulov, S. O., Azizov, V. G., Abduboqiyev, A. R., & Rakhimov, R. N. (2021). Study of the Neuroprotective Properties of Biologically Active Compounds. Annals of the Romanian Society for Cell Biology, 25(6), 2775-2782.
Khoshimov, N. N., & Nasirov, K. E. (2017). Action of Cytisinum on the Transport Mediators and Calcium Channel of Glutamatergic Neurotransmitter Systems of the NMDA Receptor. European Journal of Medicine, (5-2), 56-63.
Numonjonovich, K. N., Baxtiyarovich, K. I., Ugli, D. J. I., Salimovich, K. S., Ugli, M. A. A., Ugli, O. M. M., ... & Nurillayevich, R. R. (2024). Еffесt of Pоlyphеnоls on Сhаngеs in thе Hеmоstаtiс Systеm of Blооd Plаsmа in Hеаlthy and Mоdеl Rаts with Аlzhеimеr’s Disеаsе. Trends in Sciences, 21(9), 8081-8081.
Khoshimov, N. N., Raimova, G. M., Nasirov, K. E., Rakhimov, R. N., & Azizov, V. G. (2020). The Effect of Sp-6 On The Transport of Mediators of NMDA-Receptors and Ca 2+-channels in Synaptosomes of rat brain. European Journal of Molecular & Clinical Medicine, 7(3), 2435-2446.
Khoshimov, N. N., Kabil, N. E., & Eshbakova, K. A. (2015). Research influence biological active agents in the course of regulation of functional activity of platelets and system of a haemostasis. European Journal of Medicine, 2, 88-93.
Khoshimov, N. N., Mukhtorov, A. A., Nasirov, K. E., Rakhimov, R. N., & Mamadaminov, R. R. (2022). Effeсts of Рolyрhenols on Сhanges in the Transрort of Сa2+ NMDA-reсeрtors Under the Influenсe of L-glutamate against the Baсkground of Alzheimer’s Disease. Journal of Рharmaceutical Negative Results, 13, 1322-1332.
Khoshimov, N. N., Nasirov, K. E., Raimova, G. M., Musaeva, M. K., Azizov, V. G., Тuraev AS, M. S., ... & Abdusalоmоv Sh, A. (2021). Study of the effect of polysaccharides on hemostasis. The American journal of medical sciences and pharmaceutical research, 3(01), 131-138.
Ugli, D. J. I., Bakhtiyarovich, K. I., Numonjonovich, K. N., Erkinovich, N. K., Madmuradovna, R. G., Abdugaparovich, M. A., ... & Raxmankulovna, A. N. (2025). The Influence of Polyphenols on Calcium Dynamics in Synaptosomes of Model Rats with Attention Deficit Hyperactivity Disorder of Varying Ages. Trends in Sciences, 22(9), 10434-10434.
Download and View Statistics
Copyright License
Copyright (c) 2026 Yuldasheva G.K., Holiqova M.A., Muratova M.X., Kоzоkоv I. B., Khоshimоv N.N., Erkinov I. O., Kosimova Z.T., Rakhimov R.N., Abduganiyeva M.A.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain the copyright of their manuscripts, and all Open Access articles are disseminated under the terms of the Creative Commons Attribution License 4.0 (CC-BY), which licenses unrestricted use, distribution, and reproduction in any medium, provided that the original work is appropriately cited. The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.