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

This study demonstrated the potential of specific polyphenolic compounds in regulating hemostasis and biochemical imbalances in type 2 diabetes mellitus.

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.

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