Abstract:
Type 2 Diabetes Mellitus (T2DM) is characterized by insulin resistance and
persistent hyperglycemia. This study investigated the antidiabetic potential of 30 phenolic
and flavonoid compounds derived from Eichhornia crassipes using in silico approaches,
including toxicity assessments (ToxTree 3.1.0, ProTox 3), ADME analysis (SwissADME),
and molecular docking (AutoDock 4.2.6). Ligand structures were retrieved from
PubChem, while PPAR-γ (5Y2O) and α-Glucosidase (3TOP) receptors were obtained
from the RCSB Protein Data Bank. Toxicity and ADME analyses were conducted prior
to molecular docking, which employed the Genetic Algorithm with 50 conformations.
Docking results revealed that Tricin (a flavonoid) exhibited strong interactions with both
receptors, with Gibbs free energy values of -7.53 kcal/mol for PPAR-γ and -5.19 kcal/mol
for α-Glucosidase. These values are comparable to those of the native ligand Pioglitazone
(-10.03 kcal/mol) and Acarbose (-6.86 kcal/mol). Tricin formed hydrogen bonds and
hydrophobic contacts with key active site residues including, ARG288 and TYR327 in
PPAR-γ, GLN1561 and GLN1372 in α-Glucosidase), mirroring the interactions of the
native ligands. Toxicity predictions classified Tricin as low risk (Class I Cramer Rules,
Kroes TTC). Furthermore, ADME evaluation showed that Tricin (aglycone) is fully
compliant with Lipinski's Rule of Five, suggesting favorable properties for oral
absorption and bioavailability. In conclusion, Tricin from E. crassipes demonstrates
significant potential as an antidiabetic candidate and warrants further in vitro and in
vivo validation.
