Evaluation of the alpha-amylase inhibitory activity of Euclea natalensis extracts used in the treatment of diabetes mellitus: An experimental and in silico approach
DOI:
https://doi.org/10.14719/pst.2845Keywords:
Diabetes mellitus, α-amylase, oral starch tolerance test, Euclea natalensis, phytochemicalsAbstract
Diabetes, a chronic metabolic disorder with increasing global prevalence, poses a significant public health concern, necessitating the development of safe and effective drugs. This study specifically assessed the inhibitory effects of Euclea natalensis leaf extracts on alpha-amylase through in vitro, in vivo, and in silico methods. The extracts were sequentially obtained using solvents of graded polarity. alpha-amylase inhibition studies were conducted through spectrophotometric methods, while in vivo assessments were performed using a starch tolerance test on rats. Molecular docking was carried out using Autodock 4.2.6, and SwissADME, along with ADMETlab 2.0, were employed to determine the drug-likeness and toxicity properties of the literature-mined compounds. The extracts demonstrated significant in vitro inhibition of alpha-amylase, with the methanol extract exhibiting the highest percentage of inhibition at 27% ± 4.2, followed by hexane and aqueous extracts at 18% ± 2.5 and 18% ± 3.7, respectively. In vivo, the extracts lowered blood glucose levels, with acarbose reducing peak blood glucose levels by 42%, while both the aqueous and methanol extracts reduced it by 19% each after 30 min. The overall glucose-lowering effect, based on the area under the starch tolerance curve, ranked as follows: acarbose > methanol > aqueous > hexane > dichloromethane extract. Molecular docking identified 20(29)-lupene-3 beta-isoferulate C3 as the most promising compound with the lowest binding energy of -11.4 kcal/mol. Molecular dynamics revealed that C3 loses stability as it diverges from the active site. Additionally, while all other compounds passed the Lipinski drug-likeness criteria, 20(29)-lupene-3 beta-isoferulate C3 did not. Therefore, the present study suggests that E. natalensis exhibits antidiabetic properties through the inhibition of alpha-amylase and may serve as a source of potential antidiabetic drug molecules.
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