An in silico analysis of costunolide with specifically identified receptor proteins related to diabetes mellitus.

Costunolide, a naturally derived sesquiterpene lactone, was investigated for its potential as a multi-target antidiabetic compound using molecular docking, ADMET evaluation, and molecular dynamics (MD) simulation. Docking analysis demonstrated that Costunolide showed a strong binding affinity toward multiple diabetes-related receptors, particularly Glycogen Synthase Kinase-3β (GSK-3β) and Aldose Reductase (AR), exhibiting a good affinity compared to standard inhibitors. Also, the moderate interactions were observed with PTP-1β, DPP-Ⅳ, GLP-1R, α-glucosidase, and α-amylase, indicating its ability to modulate several anti-diabetic pathways simultaneously. ADMET assessment revealed favorable pharmacokinetic properties along with safety parameters, including good absorption and metabolic stability, supporting its suitability for oral administration. Some challenges, such as limited solubility and the need for further clarification of its excretion profile and dermal safety, warrant additional investigation. MD simulation of Costunolide -Aldose Reductase complex further indicates the stability of the interaction, as evidenced by consistent RMSD and low RMSF values, along with sustained hydrogen bonding and hydrophobic contacts within the active site. Collectively, these computational findings underscore Costunolide's potential as a stable and effective scaffold for the development of novel multi-target antidiabetic agents targeting key metabolic and inflammatory pathways. However, experimental validation and in vivo studies are necessary to substantiate its therapeutic efficacy. Overall, this study highlights the promising contribution of natural compounds in the development of innovative treatments for diabetes.