Unlocking the potential of <i>Trigonella foenum-graecum</i> L. plant leaf extracts against diabetes-associated hypertension: A proof of concept by <i>in silico</i> studies

Abstract Background The traditional plant Trigonella foenum-graecum L. has been used in the regulation of low blood glucose levels since ancient ages. Objectives Our research claimed on the potential of T. graecum L. leaf extract in treating hypertension in diabetes mellitus through various targets via molecular docking studies. Methods Diabetes-associated hypertension was induced in all rats, except the normal control group, using freshly prepared dexamethasone sodium (10 mg/kg) administered subcutaneously to overnight starved rats. Diabetic rats were orally administered chloroform and hydroethanolic extracts of T. graecum L. leaves at varying concentrations for a duration of 45 days. Biochemical, histopathological, and computational studies were investigated at the end of the treatment. Result The results of the study revealed that the hydroethanolic extract exhibited excellent protective activity against diabetes-associated hypertension. At both intervals, hydroethanolic and chloroform extracts exhibited significant ( p &lt;0.0001) reduction in systolic blood pressure levels. With respect to blood glucose levels, the chloroform (400 mg/kg) and hydroethanolic (200 mg/kg) extracts exhibited 45.7 and 47.3% reduction, respectively. High-performance liquid chromatography analysis confirmed the presence of quercetin in the serum samples of treated groups. Histopathological analysis revealed that groups treated with higher doses of extract showed cellular improvement and restoration of the normal morphological structure. Association of quercetin with PPAR-γ (peroxisome proliferator-activated receptor gamma) and ACE (angiotensin converting enzyme) gene was found to be positive for the treatment of diabetes-associated hypertension through computational analysis. Conclusions In conclusion, hydroethanolic and chloroform extracts of T. graecum L. leaves may provide novel options for the clinical management of type 2 diabetes-associated hypertension. The in silico study supports the therapeutic potential of its bioactive compounds, anticipating further pharmacological and clinical investigations.