ANK-1, ANK-2, ITL-2 Polyphenols in a Dexamethasone-Induced Rat Model of Type 2 Diabetes Mellitus Treatment
Raimova Guli Madmurodovna1, Nasirov Kabil Erkinovich1, Khodjiyev Sirojiddin Salimovich.1,Ortikov Mukhamadkodir Musajonovich1, Maxmudov Rustam Rasuljonovich2, Toshtemirova Muazzam Akmaljonovna3, Isagalieva Sadafhon Mukhammadaminovna3 ,Usmanova Muhayyokhan Sobirjonovna4
Journal of Angiotherapy 8(7) 1-8 https://doi.org/10.25163/angiotherapy.879778
Submitted: 24 May 2024 Revised: 11 July 2024 Published: 14 July 2024
Abstract
Background: Diabetes mellitus (DM) is a prevalent endocrine disorder that significantly increases the risk of cardiovascular complications due to the dysfunction of the coagulation and anticoagulation systems, exacerbated by metabolic imbalances. Despite advancements in understanding DM's pathophysiology, the precise alterations in the hemostatic system remain inadequately explored, posing challenges in diagnosis and treatment. This study investigated the effects of polyphenolic compounds isolated from Hexagalloy-lglucose (ANK-1), Hepta galloyl-glucose (ANK-2), and Isatis tinctoria L. (ITL-2) on biochemical and coagulation parameters in a dexamethasone-induced type 2 diabetes mellitus (T2DM) model in rats. Methods: T2DM was induced in 25 aged white outbred rats by administering dexamethasone (0.150 mg/kg) twice daily, with a control group receiving saline. Biochemical parameters, including glucose, total protein, ALT, AST, cholesterol, and triglycerides, were measured using a semi-automatic analyzer. Coagulation parameters such as prothrombin time (PT), activated partial thromboplastin time (APTT), plasma recalcification time (RP), and fibrinogen levels were assessed using a single-channel coagulometer. Platelet aggregation was recorded using an aggregometer, and clot degradation was measured spectrophotometrically. Results: Dexamethasone administration induced significant hyperglycemia and hypercoagulation, evidenced by reduced PT, APTT, and RP, alongside increased fibrinogen levels. The administration of ITL-2 normalized all biochemical parameters, while ANK-1 and ANK-2 normalized glucose, cholesterol, and triglycerides but not ALT and AST levels. ANK-1, ANK-2, and ITL-2 demonstrated significant antithrombotic effects, with ITL-2 showing the highest efficacy, reducing clot mass and enhancing clot degradation. Conclusion: Polyphenolic compounds, particularly ITL-2, exhibit potential as therapeutic agents for managing coagulation abnormalities and hyperglycemia in T2DM. These findings highlight the importance of further research into plant-derived substances as safer and effective alternatives in diabetes management.
Keywords: Polyphenols, Type 2 Diabetes Mellitus, Hemostasis, Dexamethasone, Hypercoagulation, Anticoagulants, Antiplatelet agents, Polyphenols.
References
Ametov, A. S., & Solov'eva, O. L. (2007). Narusheniya v sisteme gemostaza pri sakharnom diabete i puti ikh korrektsii pri naznachenii kombinirovannoy terapii Diabetonom MV i metforminom. Diabetes Mellitus, 10(3), 33-39. https://doi.org/10.14341/2072-0351-5995
Atamanov, V. M., Yakovleva, G. Y., & Tereshchenko, I. V. (2003). Narushenie sistemy gemostaza pri sakharnom diabete. Omskiy Nauchny Vestnik, (3), 58-62.
Balabolkin, M. I., Klebanov, E. M., & Kreminskaya, V. M. (2000). Patogenez i mekhanizmy razvitiya angiopatiy pri sakharnom diabete. Kardiologiya, (10), 74-87.
Barkagan, Z. S., Rudnitskaya, T. A., & Kolpakov, M. A. (2006). Narushenie obmena gomoisteina u bol'nykh sakharnym diabetom 2 tipa. Tromboz, Gemostaz i Reologiya, (3), 20-25.
Bondar, I. A., Klymentov, V. V., & Porshennikov, I. A. (2000). Okislitel'naya modifikatsiya belkov pri diabeticheskikh mikroangiopatiyakh. Sakharnyy Diabet, (3), 9-12.
Bondarenko, I. Z., & Shirshina, I. A. (2013). Mekhanizmy tromboobrazovaniya, assotsiirovannye s sakharnym diabetom: Chto opredelyaet prognoz interventsionnogo vmeshatel'stva? Sakharnyy Diabet, (3), 58-63.
Brummel, N. S., Jenny, N. S., & Mann, K. G. (2002). Molecular and cellular hemostasis and fibrinolysis. In P. Lancer & E. J. Topol (Eds.), Pan Vascular Medicine (Part 18, pp. 287-318). Springer.
Carr, M. E. (2001). Diabetes mellitus: A hypercoagulable state. Journal of Diabetes and Its Complications, 15(1), 44-54.
Hunter, R. W., & Hers, I. (2009). Insulin/IGF-1 hybrid receptor expression on human platelets: Consequences for the effect of insulin on platelet function. Journal of Thrombosis and Haemostasis, 7, 2123-2130.
Hwang, J., Kong, T., Baek, N., & Pyun, Y. (2000). Alpha-glycosidase inhibitory activity of hexagalloylglucose from the galls of Quercus infectoria. Planta Medica, 66, 273-274.
Ishida, M., Ishida, T., Ono, N., Matsuura, H., Watanade, M., Kambe, M., & Oshima, T. (1996). Effects of insulin on calcium metabolism and platelet aggregation. Hypertension, 28, 209-221.
Khoshimov, N. N., Raimova, G. M., Nasirov, K. E., Mamatova, Z. A., Mamadaliyeva, N. I., & Turaev, A. S. (2021). The effect of sulfated cellulose on the system of hemostasis. Research Journal of Pharmacy and Technology, 14(6), 3283-3289. https://doi.org/10.52711/0974-360X.2021.00571
Kirichuk, V. F., Bolotova, N. V., & Nikolaeva, N. V. (2004). Izmeneniya mikrotstsirkulyatornogo gemostaza i reologii pri sakharnom diabete. Tromboz, Gemostaz i Reologiya, (4), 12-19.
Kirichuk, V. F., Rebrov, A. P., & Kosheleva, N. V. (2002). Uglevodnaya spetsifichnost' membran trombotsitov u bol'nykh s ostrym koronarom sindromom i ego sochetaniyem s insulinnonezavisymym sakharnym diabetom. Tromboz, Gemostaz i Reologiya, (4), 61-65.
Kretova, E. Y., Kondrat'eva, E. I., & Sukhanova, G. A. (2004). Vzaimosvyaz' pokazateley sistemy gemostaza, uglevodnogo i lipidnogo obmena pri sakharnom diabete tipov 1 i 2. Klinicheskaya Laboratornaya Diagnostika, (69), 69-74.
Kretova, E. Y., Kondrat'eva, E. I., & Sukhanova, G. A. (2004). Vzaimosvyaz' pokazateley sistemy gemostaza, uglevodnogo i lipidnogo obmena pri sakharnom diabete tipov 1 i 2. Klinicheskaya Laboratornaya Diagnostika, (69), 69-74.
Lee, T.-S., & Bae, Y.-S. (2015). A gallotannin from Cercidiphyllum japonicum leaves. Journal of Korean Wood Science and Technology, 43, 558-565.
Lugovskoy, E. V. (2003). Molekulyarnye mekhanizmy obrazovaniya fibrina i fibrinoliza. Kiev: Naukovaya Dumka.
Lyutova, R. I., Alekseeva, M. A., & Karabasova, et al. (2002). Sostoyanie sistem gemokoagulyatsii i fibrinoliza u bol'nykh SD 2 tipa. Tromboz, Gemostaz i Reologiya, (2), 66-69.
Martyanov, A. A., Morozova, D. S., Khoreva, A. L., Panteleev, M. A., Shcherbina, A. Yu., & Sveshnikova, A. N. (2020). Specific features of intracellular calcium signaling, distinctive for Wiskott-Aldrich syndrome patients. Pediatric Hematology/Oncology and Immunopathology, 19(1), 100-107. https://doi.org/10.24287/1726-1708-2020-19-1-100-107
Nacag-Icindic, E., Valjevac, F., & Lepara, O. (2007). Metabolic syndrome and plasma fibrinogen in type 2 diabetic patients. Arhiv, 61(1), 7-10.
Nasirov, K. E., Ortikov, M. M., Khoshimov, N. N., Raimova, G. M., Musaeva, M. K., & Shomurodov, Sh. A. (2023). MSH-21 sulfated polysaccharide's effect on platelet-coagulation hemostasis. Infektsiya, Immunitet i Farmakologiya, 145.
Raimova, G. M., Khoshimov, N. N., Nasirov, K. E., & Turaev, A. S. (2021). Anti-thrombotic action of sulfated polysaccharides on thrombosis caused by thromboplastin. Research Journal of Pharmacy and Technology, 14(11), 6085-6088. https://doi.org/10.52711/0974-360X.2021.01057
Raimova, G. M., Nasirov, K. E., Shodmonova, D. Sh., & Khotamov, T. N., Makhmudov, R. R. (2023). Issledovanie antidiabeticheskoy aktivnosti polifenolov ANK-1, ANK-2 i ITL-2 pri modelirovanii sakharnogo diabeta 2 tipa. Infektsiya, Immunitet i Farmakologiya, (6), 103-110.
Randriamboavonjy, V., & Fleming, I. (2009). Insulin, insulin resistance, and platelet signaling in diabetes. Diabetes Care, 32, 528-530.
Sovalkin, V. I., & Paymanov, I. V. (2005). Kliniko-patogeneticheskaya otsenka trombotsitarno-sosudistogo gemostaza u patsientov s dekompensirovannym sakharnym diabetom 2 tipa. Omskiy Nauchny Vestnik, (1), 256-259.
Stratman, B., & Tschoehe, D. (2005). Pathobiology and cell interactions of platelets in diabetes. Diabetes and Vascular Disease Research, 2, 16-23.
Taiwo, B. J., Popoola, T. D., van Heerden, F. R., & Fatokun, A. A. (2020). Pentagalloylglucose, isolated from the leaf extract of Anacardium occidentale L., could elicit rapid and selective cytotoxicity in cancer cells. BMC Complementary Medicine and Therapies, 20, 287-295.
Winocour, P. D., Watala, C., Perry, D. W., & Kinlough-Rathbone, R. L. (1992). Decreased platelet membrane fluidity due to glycation or acetylation of membrane proteins. Thrombosis and Haemostasis, 68, 577-582.
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