Effects of Chamaecostus cuspidatus leaf extract and p-coumaric acid on diabetes-associated vascular injury in high-fat diet/streptozotocin- induced wistar rats

Endothelial dysfunction plays a significant role in the cardiovascular consequences of diabetes. Persistent hyperglycemia and dyslipidaemia may increase oxidative stress and inflammatory responses. The present study aimed to evaluate the effects of Chamaecostus cuspidatus leaf extract and p -coumaric acid alone and in combination in a diabetic rat model induced by a high-fat diet and streptozotocin (40 mg/kg). The effects of the treatments were examined by biochemical parameters, oxidative stress parameters, antioxidant enzyme activities, histopathology and immunohistochemical assessment of vascular morphology and immunoreactivity of TXNIP, NLRP3 and caspase-1. The analytical findings tentatively supported the presence of p -coumaric acid in the methanolic leaf extract based on FTIR, GC- MS and HPLC investigations. HPLC examination indicated a similar retention time between the extract and the authentic p -coumaric acid standard, and the calculated concentration of p -coumaric acid equivalents was 15.30 μg/mL by single-point comparison. In diabetic rats, the combination treatment was associated with improved metabolic parameters compared with the diabetic disease control, including a 74% reduction in final blood glucose, together with reductions in total cholesterol, triglycerides and an improvement in HDL-C. Treatment enhanced antioxidant defence, with SOD, CAT, GSH and GPx increasing by 41%–100%, and decreased oxidative-stress indicators, such as ROS and MDA, by 38%–53%. Histopathological examination demonstrated comparatively preserved vascular architecture, accompanied by reduced TXNIP, NLRP3, and caspase-1 immunoreactivity. This finding suggests altered expression of inflammation-associated markers together with improvements in metabolic and oxidative state. In conclusion, combination therapy of C. cuspidatus leaf extract and p -coumaric acid exhibited positive effects on the vascular alterations associated with diabetes and may deserve further exploration as a combination method.