Investigation of the Hypoglycemic Potential of Methanolic Extract of Piper Sylvaticum Against Streptozotocin-Induced Mice and in Silico Study

Abstract

Introduction: Diabetes mellitus (DM) remains a substantial challenge to global healthcare systems, underscoring the need for therapeutic strategies with improved safety profiles.

Objectives: The present investigation explored the antidiabetic efficacy of a crude methanolic extract derived from Piper sylvaticum Roxb. (MEPS) using a streptozotocin-induced murine model of diabetes, while concurrently interrogating putative molecular mechanisms through in silico computational analyses.

Methods: STZ (Streptozotocin, 45 mg/kg b.w.) was administered intraperitoneally to Swiss albino mice to cause diabetes. Metformin hydrochloride (10 mg/kg) and MEPS (250 and 500 mg/kg) were administered orally once daily for three weeks. The sugar level and biochemical markers such as lipid profile, SGPT, and uric acid were determined by enzyme linked immunosorbent assay technique. An in silico study was conducted using a computer-aided model with the α-amylase enzyme. 

Results: Acute toxicity tests confirmed safety up to 2500 mg/kg. MEPS at 250 and 500 mg/kg significantly lowered fasting blood glucose, enhanced oral glucose tolerance, and prevented body weight loss compared to diabetic controls. Biochemical tests showed decreases in serum SGPT, cholesterol, LDL, and triglycerides, with a slight increase in HDL, indicating hepatoprotective and antihyperlipidemic effects. Molecular docking identified sylvatesmin, piperine, and sylvone as strong α-amylase inhibitors (binding energies –8.5, –7.9, and –7.2 kcal/mol) further supported by favorable ADME and toxicity profiles.

Conclusions: These results highlight P. sylvaticum as a promising source of lead compounds for the development of safer, plant-based antidiabetic therapies.