Carvacrol from Moringa oleifera as a potential antidiabetic agent using integrated in-silico approach inhibiting TCF7L2.

Diabetes mellitus is a major health concern worldwide; lifestyle and rising urbanization are the key contributing factors. The genetic factors implicated in type 2 diabetes include the transcription factor 7-like 2 (TCF7L2) gene on chromosome 10q25.3, which has been greatly linked with diabetes, but the mechanisms and therapeutic effect on this gene are yet to be clearly defined. The objective of the research was to discover and screen natural phytochemicals of Moringa oleifera, especially carvacrol, as promising TCF7L2 inhibitors through combined in-silico methods. We have used a computational pipeline that includes ADMET profiling, molecular docking, molecular, dynamics (MD) simulations, and density functional theory (DFT) analysis. The ADMET analysis demonstrated that carvacrol has desirable pharmacokinetics, such as high gastrointestinal absorption, drug-likeness, and low-predicted oral toxicity. Molecular docking studies showed that carvacrol has a high binding affinity with the TCF7L2 protein with a binding energy of -5.5 kcal/mol. The conformational stability of the carvacrol-TCF7L2 complex was further validated through an extended 200 ns MD simulation, where the protein backbone RMSD stabilized after ~ 40 ns within ~ 0.25–0.35 nm (2.5–3.5 A), while the ligand RMSD remained consistently low at ~ 0.01–0.02 nm (0.1–0.2 A), supported by a persistent hydrogen-bond network throughout the trajectory. The chemical stability and reactivity of the compound were confirmed by DFT calculations. These findings indicate that carvacrol has potential as a lead compound against TCF7L2 in the treatment of type 2 diabetes. These results are in support of the therapeutic relevance of carvacrol, though experiments are necessary to prove its efficacy and safety in biological systems.