Antidiabetic, Hepato‐Nephroprotective, and Antioxidant Properties of Medicinal Plants Validated by Phytochemical and Molecular Docking Analyses

Abstract

The study investigated the phytochemical composition, antioxidant activity, antidiabetic efficacy, safety, and organ‐protective potential of Silybum marianum ( S. marianum ) and Citrullus colocynthis ( C. colocynthis ) seed extracts through integrated in vivo and in silico approaches. HPLC analysis identified major bioactive compounds, including gallic acid, caffeic acid, sinapic acid, myricetin, and quercetin. Antioxidant assays demonstrated superior radical scavenging and reducing capacities in S. marianum , which also exhibited higher total phenolic and flavonoid contents than C. colocynthis . Alloxan‐induced diabetic rats were allocated into five groups: normal control, diabetic control, S. marianum ‐treated, C. colocynthis ‐treated, and combined‐treatment groups receiving 250 mg/kg extracts. Treatment significantly reduced blood glucose, improved lipid metabolism, normalized hepatic and renal biomarkers, and enhanced body weight compared with diabetic controls. Histopathological examination revealed restoration of hepatic, and renal architecture, particularly in animals receiving S. marianum or the combined treatment. Acute and subacute toxicity studies demonstrated no mortality or treatment‐related adverse effects up to 5000 mg/kg, indicating a favorable safety profile. Molecular docking further confirmed strong interactions of the identified phytochemicals with α‐amylase, CYP2E1, and GSTA1, supporting their potential mechanisms of action. Overall, these findings demonstrate that S. marianum and C. colocynthis represent safe and promising nutraceutical candidates for the management of diabetes and its associated complications.