Abstract

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.

Key words: Ankyrin-1, Plant phenols, Rats, Type 2 diabetes, Vascular alterations