Prospective role of lupeol from Pterocarpus santalinus leaf against diabetes: An in vitro, in silico, and in vivo investigation

Diabetes mellitus (DM) can be treated with various medications. However, individuals in underdeveloped countries may face challenges in using these treatments due to side effects and high costs. Anti-diabetic medications can inhibit enzymes, such as α-amylase, which is responsible for breaking down carbohydrates. In this investigation, 16 phytoconstituents were identified from Pterocarpus santalinus leaf extract through GC-MS analysis, and their significant antioxidant activities were noted. Among these, the pure compound lupeol demonstrated α-amylase inhibition activity of 86.13 ± 1.27 % (IC₅₀ = 58.50 ± 0.83 μg/mL) in vitro. Additionally, lupeol showed the highest binding affinity in silico using PyRx and CB-Dock, with values of -9.5 and -9.3 kcal/mol, respectively. The in silico analysis also indicated that lupeol possesses acceptable ADMET properties, suggesting its potential as an anti-diabetic drug. A molecular dynamics simulation lasting 500 ns was conducted to evaluate hydrogen bonds, RMSF, RMSD, Rg, and SASA, confirming the stability and integrity of the docking scenarios. In STZ-induced diabetic mice, lupeol significantly reduced blood glucose levels by 70.82 % from day 0 to day 28. Furthermore, lupeol markedly decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while improving high-density lipoprotein cholesterol (HDL-C) levels in these mice. The antidiabetic effect of lupeol was further validated through histological examinations of the pancreas, heart, kidney, and liver of treated mice, alongside correlation analysis, CAP, and ANOSIM tests. Based on the findings from the in vitro, in silico, and in vivo investigations, this study concludes that lupeol may have potential anti-diabetic effects through the inhibition of the α-amylase enzyme.