Antidiabetic Activity of Phenolic‐Rich Extracts From Cistus albidus (L.) in Alloxan‐Induced Diabetic Rats: In Vitro , In Vivo , and In Silico Investigations

ABSTRACT Diabetes, a prevalent metabolic disorder, has prompted extensive research into natural remedies with hypoglycemic potential and minimal side effects. The aim of this study was to examine phenolic compounds using high‐performance liquid chromatography (HPLC). Acute toxicity was assessed in mice following OECD 423 criteria, and anti‐diabetic potential was tested by intraperitoneal injection of alloxan (150 mg/kg) to induce experimental diabetes. Acute toxicity assessment found no adverse effects, while chemical analysis revealed various phenolic compounds like rutin, quercetin, and gallic acid, known for their therapeutic properties. In vitro experiments with the aqueous extract showed significant inhibition of pancreatic α ‐amylase enzyme activity (IC 50 value: 119.813 ± 3.827 μg/mL). In vivo studies demonstrated the extract's efficacy in mitigating body weight loss, promoting hypoglycemic effects, and improving oral glucose tolerance. Additionally, the extract regulated biochemical parameters including total cholesterol, triglycerides, liver enzymes, and renal markers. These findings suggest that Cistus albidus leaf polyphenols possess anti‐hyperglycemic and α‐amylase inhibitory properties, supporting its traditional use in diabetes treatment and potential incorporation into future antidiabetic medications. Molecular docking analysis further supported the interaction of extract constituents with relevant target proteins, offering insights into potential therapeutic interventions.