Bio‑enhancing Effect of Piperine with Metformin on Lowering Blood Glucose Level in Alloxan Induced Diabetic Mice

Background: Diabetes mellitus is the most rampant metabolic pandemic of the 21^st century. Piperine, the chief alkaloid of Piper nigrum (black pepper) is widely used in alternative and complementary therapies has been extensively studied for its bio‑enhancing property. Objective: To evaluate the bio‑enhancing effect of piperine with metformin in lowering blood glucose levels in alloxan‑induced diabetic mice. Materials and Methods: Piperine was isolated from an extract of fruits of P. nigrum. Alloxan‑induced (150 mg/kg intraperitoneal) diabetic mice were divided into four groups. Group I (control 2% gum acacia 2 g/100 mL), Group II (metformin 250 mg/kg), Group III (metformin and piperine 250 mg/kg + 10 mg/kg), and Group IV (metformin and piperine 125 mg/kg + 10 mg/kg). All the drugs were administered orally once daily for 28 days. Blood glucose levels were estimated at day 0, day 14, and end of the study (day 28). Results: The combination of piperine with therapeutic dose of metformin (10 mg/kg + 250 mg/kg) showed significantly more lowering of blood glucose level as compared to metformin alone on both 14t^h and 28^th day (P < 0.05). Piperine in combination with sub‑therapeutic dose of metformin (10 mg/kg + 125 mg/kg) showed significantly more lowering of blood glucose as compared to control group and also showed greater lowering of blood glucose as compared to metformin (250 mg/kg) alone. Conclusion: Piperine has the potential to be used as a bio‑enhancing agent in combination with metformin which can help reduce the dose of metformin and its adverse effects.