Effect of Ankyrin-1 polyphenol on vascular alterations in type 2 diabetes mellitus in rats Guli Raimova, Nozim Khoshimov, Kabil Nasirov, Siroj Khodjiev, Rustam Makhmudov, et al. Journal of Advanced Biotechnology and Experimental Therapeutics, 2026 Type 2 diabetes mellitus (T2DM) is strongly associated with endothelial dysfunction, altered vascular reactivity, and a prothrombotic shift in hemostasis, which together increase the risk of cardiovascular complications. Plant polyphenols have attracted attention as multifunctional bioactive molecules with antioxidant and anti-inflammatory properties. This study evaluated the corrective effect of the polyphenol ANK-1 (isolated from Pistacia vera L.) on vascular dysfunction and hemostatic/platelet alterations in rats with experimentally induced T2DM, with metformin used as a reference drug. T2DM was induced in outbred male albino rats by 60-day high-fat feeding followed by a single intraperitoneal injection of streptozotocin (35 mg/kg; 0.1 M citrate buffer, pH 4.5). Biochemical indices (glucose, ALT, AST, total cholesterol, triglycerides, insulin, HOMA-IR), coagulation tests (PT, APTT, plasma recalcification time, fibrinogen), and platelet aggregation (ADP, collagen, epinephrine) were assessed. Vascular reactivity of isolated aortic rings was examined using KCl- and phenylephrine-induced contractions and concentration-dependent vasorelaxation, including endothelium-denuded conditions and pharmacological inhibition (L-NAME, methylene blue, indomethacin). The T2DM model produced hyperglycemia, dyslipidemia, increased transaminase activity, hypercoagulation, and enhanced platelet aggregation. Oral ANK-1 (10 mg/kg, 10 days) improved glycemic and lipid parameters, attenuated hypercoagulability, and reduced ADP-, collagen-, and epinephrine-induced platelet aggregation. In aortic rings, ANK-1 partially restored contractile responses and produced marked vasorelaxation that was reduced after endothelial removal and in the presence of L-NAME and methylene blue, indicating involvement of the NO/sGC/cGMP pathway. ANK-1 demonstrates vasoprotective and antithrombotic potential in experimental T2DM, likely mediated by endothelium-dependent mechanisms linked to NO signaling and modulation of Ca²⁺-dependent vascular and platelet activation.
Effect of Polyphenols on the Hemostatic System in Rats with Streptozotocin-Induced Type II Diabetes Guli Raimova, Siroj Khodjiyev, Kabil Nasirov, Nozim Khoshimov, Mukhamatkodir Ortikov, et al. Biomedical and Pharmacology Journal, 2025 In type 2 diabetes mellitus, all hemostatic systems involved in blood clotting, regulation of vascular tone, the condition of blood cells, and plasma enzyme systems are activated. In this disease, there is a clear correlation between hemocoagulation disorders and the degree of glycemia. In this regard, an important and urgent task is to study these mechanisms and to search for new drugs that can prevent further progression. In this study, experiments on model rats were conducted to test the effects of polyphenols as antidiabetic agents. Polyphenol-containing foods and beverages such as coffee, guava tea, blueberries, olive oil, propolis, chocolate, red wine, grape seeds, and cocoa have been shown to exert beneficial effects in individuals with type 2 diabetes mellitus. These compounds contribute to better glucose regulation, enhance vascular health, reduce insulin resistance, and help lower HbA1c levels, thereby potentially mitigating both the progression and complications of diabetes, including alterations in the hemostatic system. This paper presents a study of polyphenol preparations isolated from the Pistacia vera plant (compound ANK-1), the Karelinia caspia plant (compound KCL-1), and an extract from the Isatis tinctoria L. plant (compound ITL-2), and their effects on biochemical parameters and the blood-clotting system in rats with experimentally induced type 2 diabetes caused by streptozotocin.
The Influence of Polyphenols on Calcium Dynamics in Synaptosomes of Model Rats with Attention Deficit Hyperactivity Disorder of Varying Ages Dеdаbоеv Jobir Ismoil Ugli, Kоzоkоv Islom Bakhtiyarovich, Khоshimоv Nozim Numonjonovich, Nаsirоv Kabil Erkinovich, Raimova Guli Madmuradovna, et al. Trends in Sciences, 2025 Intrоduсtiоn: ADHD is characterized by disrupted neuronal excitability, often associated with dysregulated calcium (Ca²⁺) signaling. We investigated the effects of the polyphenol ANK-2 on intracellular Ca²⁺ dynamics in synaptosomes isolated from the brains of healthy and ADHD-model rats of different ages. Mаtеriаls аnd Mеthоds: In the studies, rats weighing 150 - 200 g were subjected to an ADHD model by administering 6-OHDA at 2 different doses of 8 and 4 mg/kg orally for 14 days using a special probe. Also, in order to induce the АDHD model in the prenatal period in young rats, it was first established that rats of both sexes were placed together, their condition was determined using a swab, and then, on average 3 - 4 days before birth, CdCl₂ was dissolved (50 ppm) and administered orally to pregnant rats weighing 200 - 250 g using a special probe, as a result of which the ADHD model was manifested in the offspring. Using the calcium-sensitive fluorescent probe Fluo-4AM, we found that ANK-2 significantly reduced cytosolic Ca²⁺ levels in a dose-dependent manner. Results and discussion: In ADHD models, baseline Ca²⁺ content was markedly elevated compared to age-matched controls, consistent with hyperactive synaptic transmission. GABA (100 μM) decreased [Ca²⁺] in by 14 % in healthy rats and 20 % in ADHD rats, suggesting enhanced compensatory GABAergic inhibition in the ADHD condition. Co-incubation with ANK-2 (10 - 100 μM) further suppressed calcium influx, indicating a synergistic enhancement of GABAergic effects. Additionally, ANK-2 potentiated the calcium-lowering effect of levetiracetam (5 μM), a selective N-type Ca²⁺ channel blocker, further reducing cytosolic Ca²⁺ levels. Соnсlusiоns: These findings suggest that ANK-2 acts through multiple mechanisms, including enhancement of GABAergic signaling, direct or indirect inhibition of voltage-gated calcium channels, and modulation of neurotransmitter release. Our results position ANK-2 as a promising candidate for correcting excitatory-inhibitory imbalance in ADHD by targeting calcium-dependent synaptic transmission. HIGHLIGHTS 6-OHDA selectively damages dopaminergic and noradrenergic neurons, mimicking ADHD-like hyperactivity. Provide a description for each abbreviation at the beginning: Dopamine (DA) levels alter voltage-gated calcium channels (VGCC) and intracellular calcium buffering, leading to abnormal calcium influx. 6-OHDA induces dopaminergic neurodegeneration, particularly in the mesocortical and nigrostriatal pathways. This results in compensatory activation of glutamate receptors and VGCC in postsynaptic neurons, resulting in an increase in intracellular Ca²⁺. On the other hand, cadmium chloride disrupts calcium channels (e.g., L-type Ca2+ channels) and calcium-dependent functions in mitochondria, which aggravates synaptic dysfunction. Cd²⁺ mimics Ca²⁺ and blocks Ca²⁺ ATPases and Na⁺/Ca²⁺ exchangers, disrupting calcium transport. Impaired Ca²⁺ buffering and elevated synaptosomal calcium levels cause oxidative stress and mitochondrial dysfunction. The results of behavioral tests on rats with ADHD model during our experiments show that in the control groups the experimental animals were very active and hyperactive in the Open Field test, moved quickly and hardly stood still. At the same time, the model showed that the ADHD groups were very hyperactive, with nervous system processes being activated, while the animals remained motionless. The polyphenol ANK-2 significantly reduces intracellular calcium levels in Fluo-4 AM synaptosome suspensions from rat brains of different ages. This may explain that polyphenol ANK-2 enhances the inhibitory effect of GABA (gamma-aminobutyric acid), helping to reduce neuronal excitability, or probably acts as a direct or indirect modulator of presynaptic calcium channels, particularly N-type Ca²⁺ channels, thereby reducing calcium influx. GRAPHICAL ABSTRACT
Anti-thrombotic action of sulfated polysaccharides on thrombosis caused by thromboplastin Guli M. Raimova, Nozim N. Khoshimov, Kabil E. Nasirov, Abbaskhan S. Тuraev, Malokhat E. Savutova Research Journal of Pharmacy and Technology, 2021 The antithrombotic effect of modified sulfated polysaccharides on a model of thromboplastin-induced thrombosis was investigated, which made it possible to evaluate the effectiveness of sulfated polysaccharides as a direct anticoagulant that increases the tolerance of animals to effects causing intravascular thrombosis.
The effect of sulphated cellulose on system of haemostasis Nozim N. Khoshimov, Guli M. Raimova, Kabul E. Nasirov, Zulayho A. Mamatova, Nodira I. Mamadaliyeva, et al. Research Journal of Pharmacy and Technology, 2021 Experimental studies and analyses of new compounds with different mechanisms of action on systemic haemostasis are relevant for the identification and development of potential pharmacological preparations. The modified sulphated polysaccharides with anticoagulant and antithrombin activity were studied for haemostasis. Platelet-rich plasma was obtained by centrifugation at 200g for 10 minutes. The remaining citrate blood was further centrifuged at 1500g for 10 min to obtain platelet-poor plasma. The antithrombin activity of the compounds was evaluated In vitro by their effect on the recalcification time, thrombin and prothrombin time of rabbit and human blood plasma stabilized with a 3.8% sodium citrate solution in the ratio 9:1. The results showed that the anticoagulant activity of the studied sulphates increased with an increasing degree of sulphation. Sulphated polysaccharides showed strong anticoagulant activity In vitro. The experimental results showed a significant increase in the coagulation time of blood plasma in tests for prothrombin and thrombin time. These properties of these components are of particular interest, and further detailed studies of the physicochemical characteristics and mechanisms of action of these molecules should be performed, which will eventually allow them to be used as heparin-like drugs.
RECENT SCHOLAR PUBLICATIONS
Effect of Polyphenols on the Hemostatic System in Rats with Streptozotocin-Induced Type II Diabetes G Raimova, S Khodjiyev, K Nasirov, N Khoshimov, M Ortikov, ... Biomedical and Pharmacology Journal 18 (4), 2975-2984 , 2025 2025.0
Changes in the regulation of Ca2+ signaling in synaptosomes in Alzheimer’s disease AA Mukhtorov, NN Khoshimov, KE Nasirov, TS Saatov, MA Mustafakulov, ... SPAST Abstracts 2, 5045 , 2024 2024.0 Citations: 2
DETERMINATION OF ACUTE TOXICITY D-38, KS-39 AND R-37 POLYSACCHARIDES GM Raimova, AM Ulugbek, KE Nasirov, NN Khoshimov, SD Sh 2023.0
Anti-thrombotic action of sulfated polysaccharides on thrombosis caused by thromboplastin GM Raimova, NN Khoshimov, KE Nasirov, AS Turaev, ME Savutova Research Journal of Pharmacy and Technology 14 (11), 6085-6088 , 2021 2021.0 Citations: 16
The effect of Sulphated cellulose on System of Haemostasis NN Khoshimov, GM Raimova, KE Nasirov, ZA Mamatova, ... Research Journal of Pharmacy and Technology 14 (6), 3283-3289 , 2021 2021.0 Citations: 17
Study of the effect of polysaccharides on hemostasis NN Khoshimov, KE Nasirov, GM Raimova, MK Musaeva, VG Azizov, ... The American journal of medical sciences and pharmaceutical research 3 (01 … , 2021 2021.0 Citations: 8
The Effect of Sulphated Cellulose on Haemostasis. AТS Khoshimov N.N., Raimova G.M., Nasirov K.E. Jour of Med, 17-26 , 2020 2020.0
Influence of some sulphated polysaccharides on the platelet aggregation in normal and in patients with ischemic heart disease MBI Nasirov K.E., Musaeva M.K., Khoshimov N.N., Raimova G.M., Turaev A.S. International Journal of Psychosocial Rehabilitation, 6976 - 6985 , 2020 2020.0 Citations: 4
The Effect of Sp-6 On The Transport of Mediators of NMDA-Receptors and Ca 2+-channels in Synaptosomes of rat brain NN Khoshimov, GM Raimova, KE Nasirov, RN Rakhimov, VG Azizov European Journal of Molecular & Clinical Medicine 7 (3), 2435-2446 , 2020 2020.0 Citations: 9
Selection and study of influence of preparation “CMC” on the process of cooking of blood.of influence of preparation “CMC” on the process of cooking of blood. NKE Raimova G.M., Musaeva M.K., Khoshimov N.N., Vypova N.L. Journal of Biological Research, 16-22 , 2019 2019.0
Heparin-like activity of sulfated polysaccharides NKE Nadjimova H.K.,Hoshimov N.N.,Musayeva M.K., Raimova G.M., Muxitdinov B.I. Infection, immunity and pharmacology, 44-51 , 2019 2019.0
Investigation of the anticoagulant properties of the preparations Moldy clover concentrate and 0,0-Dialkyl thiophosphate BBN Raimova G.M., Кhoshimov N.N., Nasirov K.E. Uzbek Biological Journal., 3–7 , 2017 2017.0
The influence of some biologically active compounds on the hemostatic system MAD Raimova G.M., Кhoshimov N.N., Nasirov K.E. Infection, immunity and pharmacology., 140–150 , 2016 2016.0
The effect of СMC (Melilotus) on the blood coagulation system of rats in vitro NKE 1. Raimova G.M., Кhoshimov N.N. Infection, immunity and pharmacology., 133–140 , 2016 2016.0
Isolation and physical and chemical characteristics of anticoagulants from the fire–blind clever trifolieae ZJF Raimova G.M., Кhoshimov N.N., Nasirov K.E. European Science Review, P.7–10 , 2016 2016.0
Studying anticoagulant property of the GLAS of in vitro in system of a hemostasis GM Raimova, NN Khoshimov БГМУ , 2016 2016.0 Citations: 1
Comparison of Hemostatic and Neuro Protector Properties of Alkaloids N-Metiltsitizin and a Desoxypeganin in the Conditions of in Vitro NN Khoshimov, GM Raimova, KE Nasirov, VI Vinogradova European Journal of Medicine, 155-169 , 2015 2015.0
EFFECT OF DEXTRAN AND STARCH DERIVATIVES ON PLATELET AGGREGATION IN CARDIOVASCULAR DISEASES MM Ortikov, ZA Abdurakhmanov, KE Nasirov, GM Raimova, ...
THE EFFECT OF NMSH-21 SULFATED POLYSACCHARIDE ON PLATELET COAGULANT HEMOSTASIS MM Ortikov, KE Nasirov, NN Khoshimov, GM Raimova, JI Dedaboev, ...
MOST CITED SCHOLAR PUBLICATIONS
The effect of Sulphated cellulose on System of Haemostasis NN Khoshimov, GM Raimova, KE Nasirov, ZA Mamatova, ... Research Journal of Pharmacy and Technology 14 (6), 3283-3289 , 2021 2021.0 Citations: 17
Anti-thrombotic action of sulfated polysaccharides on thrombosis caused by thromboplastin GM Raimova, NN Khoshimov, KE Nasirov, AS Turaev, ME Savutova Research Journal of Pharmacy and Technology 14 (11), 6085-6088 , 2021 2021.0 Citations: 16
The Effect of Sp-6 On The Transport of Mediators of NMDA-Receptors and Ca 2+-channels in Synaptosomes of rat brain NN Khoshimov, GM Raimova, KE Nasirov, RN Rakhimov, VG Azizov European Journal of Molecular & Clinical Medicine 7 (3), 2435-2446 , 2020 2020.0 Citations: 9
Study of the effect of polysaccharides on hemostasis NN Khoshimov, KE Nasirov, GM Raimova, MK Musaeva, VG Azizov, ... The American journal of medical sciences and pharmaceutical research 3 (01 … , 2021 2021.0 Citations: 8
Influence of some sulphated polysaccharides on the platelet aggregation in normal and in patients with ischemic heart disease MBI Nasirov K.E., Musaeva M.K., Khoshimov N.N., Raimova G.M., Turaev A.S. International Journal of Psychosocial Rehabilitation, 6976 - 6985 , 2020 2020.0 Citations: 4
Changes in the regulation of Ca2+ signaling in synaptosomes in Alzheimer’s disease AA Mukhtorov, NN Khoshimov, KE Nasirov, TS Saatov, MA Mustafakulov, ... SPAST Abstracts 2, 5045 , 2024 2024.0 Citations: 2
Studying anticoagulant property of the GLAS of in vitro in system of a hemostasis GM Raimova, NN Khoshimov БГМУ , 2016 2016.0 Citations: 1
Effect of Polyphenols on the Hemostatic System in Rats with Streptozotocin-Induced Type II Diabetes G Raimova, S Khodjiyev, K Nasirov, N Khoshimov, M Ortikov, ... Biomedical and Pharmacology Journal 18 (4), 2975-2984 , 2025 2025.0
DETERMINATION OF ACUTE TOXICITY D-38, KS-39 AND R-37 POLYSACCHARIDES GM Raimova, AM Ulugbek, KE Nasirov, NN Khoshimov, SD Sh 2023.0
The Effect of Sulphated Cellulose on Haemostasis. AТS Khoshimov N.N., Raimova G.M., Nasirov K.E. Jour of Med, 17-26 , 2020 2020.0
Selection and study of influence of preparation “CMC” on the process of cooking of blood.of influence of preparation “CMC” on the process of cooking of blood. NKE Raimova G.M., Musaeva M.K., Khoshimov N.N., Vypova N.L. Journal of Biological Research, 16-22 , 2019 2019.0
Heparin-like activity of sulfated polysaccharides NKE Nadjimova H.K.,Hoshimov N.N.,Musayeva M.K., Raimova G.M., Muxitdinov B.I. Infection, immunity and pharmacology, 44-51 , 2019 2019.0
Investigation of the anticoagulant properties of the preparations Moldy clover concentrate and 0,0-Dialkyl thiophosphate BBN Raimova G.M., Кhoshimov N.N., Nasirov K.E. Uzbek Biological Journal., 3–7 , 2017 2017.0
The influence of some biologically active compounds on the hemostatic system MAD Raimova G.M., Кhoshimov N.N., Nasirov K.E. Infection, immunity and pharmacology., 140–150 , 2016 2016.0
The effect of СMC (Melilotus) on the blood coagulation system of rats in vitro NKE 1. Raimova G.M., Кhoshimov N.N. Infection, immunity and pharmacology., 133–140 , 2016 2016.0
Isolation and physical and chemical characteristics of anticoagulants from the fire–blind clever trifolieae ZJF Raimova G.M., Кhoshimov N.N., Nasirov K.E. European Science Review, P.7–10 , 2016 2016.0
Comparison of Hemostatic and Neuro Protector Properties of Alkaloids N-Metiltsitizin and a Desoxypeganin in the Conditions of in Vitro NN Khoshimov, GM Raimova, KE Nasirov, VI Vinogradova European Journal of Medicine, 155-169 , 2015 2015.0
EFFECT OF DEXTRAN AND STARCH DERIVATIVES ON PLATELET AGGREGATION IN CARDIOVASCULAR DISEASES MM Ortikov, ZA Abdurakhmanov, KE Nasirov, GM Raimova, ...
THE EFFECT OF NMSH-21 SULFATED POLYSACCHARIDE ON PLATELET COAGULANT HEMOSTASIS MM Ortikov, KE Nasirov, NN Khoshimov, GM Raimova, JI Dedaboev, ...