Identification and evaluation of putative type 2 diabetes mellitus inhibitors derived from Cichorium intybus

Abstract

Diabetes, triggered by impaired glucose regulation, is characterized by the conversion of glucose to sorbitol by aldose reductase (AR). In prior studies to develop AR inhibitors, the toxicity and efficacy of the therapeutic molecules presented challenges throughout clinical trials. This led the researchers to investigate the potential biological modulation of natural products owing to their varied chemical structures. Cichorium intybus L. (C. intybus), commonly known as chicory, has a long history of medicinal use and shows potential pharmacological properties, particularly in reducing lipid levels. The study employs computational methods, including ADMET profiling, molecular docking, and molecular dynamics (MD) simulation, to discover possible inhibitors of ALR-2 from C. intybus. The ADMET-filtered compounds from C. intybus show high binding energy viz, CID 8468: -133.295,370: -118.633, -109.479, and 359: -108.48 Kcal/mol. These compounds were observed to exhibit strong affinity and specificity for ALR-2 as comparable to epalrestat. MD simulation of the compounds 8468 and 370 for 100 ns, further authenticated the stability of their complexes with ALR2. The RMSD, RMSF, and intra-molecular interactions of the compounds were comparable to the native ligand-epalrestat, suggesting their potential to be considered as ALR2 inhibitors. Additional research including in vitro, in vivo analysis, and clinical trials is essential to accurately assess the efficacy of natural compounds.