Exploring the Therapeutic Potential of Leea Indica Leaf Extract in Diabetic Mice: In Vivo, Phytochemical Analysis, and Molecular Interaction Studies

Diabetes mellitus remains a global health challenge, with limited effective treatments that address its root causes, including insulin resistance and insulin deficiency. The increasing prevalence of diabetes has required the exploration of alternative treatments, particularly from natural sources. Leea indica, a plant known for its medicinal properties, has gained attention for its potential antidiabetic effects. However, there is limited research exploring its therapeutic potential through comprehensive in vivo, phytochemical, and molecular docking studies. This study aimed to evaluate the antidiabetic effects of Leea indica leaf extract in a model of diabetic mice and explore its molecular mechanisms through docking studies. In vivo, results demonstrated that Leea indica extract significantly reduced insulin resistance and improved blood glucose regulation in a dose-dependent manner, with the 100 mg dose being particularly effective in lowering glucose levels to near-normal ranges. Histopathological analysis showed that the extract offered protective effects on pancreatic tissue, especially at moderate doses. Furthermore, molecular docking studies revealed that Leea indica ligands, NL and S18, exhibited stronger binding affinities for PPAR alpha compared to Acarbose, with the ligand S18 showing a particularly favorable ΔG of −10.6 kcal/mol and Ki of 0.01703 μM. These findings highlight the therapeutic potential of Leea indica leaf extract as a promising agent for the treatment of diabetes, with its phytochemicals showing favorable interactions at the molecular level. More research is needed to optimize the dose and understand the mechanisms of action that underlie its antidiabetic effects. HIGHLIGHTS The study found that Leea indica leaf extract significantly reduced insulin resistance and helped regulate blood glucose levels in diabetic mice. The 100 mg dose was particularly effective, showing promising potential for managing diabetes. Histopathological analysis revealed that Leea indica leaf extract provided protective effects on pancreatic tissue, especially at moderate doses. This suggests that the extract could help maintain pancreatic health in diabetic conditions. Molecular docking studies identified two specific phytochemicals, NL and S18, within the extract, which showed stronger binding affinities for PPAR alpha receptors compared to Acarbose, a commonly used antidiabetic drug. This highlights the potential of these compounds as effective alternatives for diabetes treatment. GRAPHICAL ABSTRACT