Abstract Description

Diabetes mellitus (DM) is an established risk factor for the development of cardiovascular diseases, with athero-thrombotic events accounting for up to 80 % of deaths in patients with Type 2 diabetes (T2DM). T2DM pathophysiology includes an accelerated risk of atherosclerosis development, a hypercoagulative state, and hypofibrinolysis. Anticoagulant therapy is one approach for preventing and treating cardiovascular diseases related to diabetes. Warfarin is the commonly used anticoagulant; however, it has many limitations. Other anticoagulants are therefore being sought, and complementary and alternative medications are one of the potential sources. Cannabis sativa has demonstrated an in vitro antithrombotic potential, an in vivo anticoagulant, and atherogenic index-lowering effects on both lean and obese rats according to Coetzee et al. (2007), with more pronounced effects in the obese rats. This study investigates the suggested potential uses of C. sativa for treating the hypercoagulative state of diabetic mellitus and the antithrombotic potential of cannabinoids. The diet-induced rat model, induced using either a high-carbohydrate diet (HCD) or a high-fat diet (HFD), and the diabetic rat model, induced with a HFD and a streptozocin injection, were used to investigate the therapeutic effects of C. sativa. Plasma samples from treatment groups were analysed for triacylglycerols, low-density lipoprotein, and total cholesterol alongside their diabetic controls to calculate and evaluate effects on the atherogenic index. Coagulation tests, including the prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and the D-dimer assay, were used to evaluate effects on coagulation pathways. Thrombin molecular docking will be used to investigate the antithrombotic potential of the cannabinoids. C. sativa treatment showed statistically significant prolongation of PT and aPTT relative to diabetic controls in both the diet-induced and diabetic rat models. This indicates an anticoagulant potential on the extrinsic and intrinsic pathways of coagulation, respectively. Treatment also shows diet-specific effects, with greater PT and aPTT anticoagulant potential on HCD compared to HFD. Only the HCD-induced rat model showed statistically significant prolongation of TT, indicating an antithrombotic potential, and elevation of D-dimer levels relative to its diabetic controls, suggesting normalising effects of C. sativa on the hypofibrinolytic state. The results obtained suggest that C. sativa has anticoagulant effects on the hypercoagulative state of diabetes. The diet-specific effects of C. sativa suggest stage-specific effects. The HCD simulates a prediabetic state in which C. sativa has anticoagulant, antithrombotic, and normalising effects on fibrinolysis. While HFD with or without streptozocin simulates T2DM, in which only anticoagulant potential is observed.