Inhibitor discovery from pomegranate rind for targeting human salivary α-amylase

Abstract

This study explored the effects of the main active compounds of the pomegranate (Punica granatum L.) rind extract on the activity of the human salivary α-amylase and their molecular inhibitory mechanisms. Four compounds exhibited remarkable inhibitory activities against α-amylase, including (1) rutin, (2) luteolin, (3) quercetin, and (4) kaempferol. The IC50 values were found to be 265.65, 59.67, 99.56, and 139.72 μM for rutin, luteolin, quercetin, and kaempferol, respectively. The kinetic study using the Lineweaver–Burk revealed the four compounds showed a non-competitive inhibition against α-amylase. However, the exact localization of the binding site and the potentiation mechanism at the molecular level are presently unknown. We have performed the “blind docking” of four compounds on the human salivary α-amylase. The molecular modeling demonstrated a high affinity and tight binding capacity of these compounds at the binding site of α-amylase, where the Glu 233 was supposed to play a key role in exerting the inhibition activity of these compounds. The results may provide an important insight for the applications of computational methods in the drug design with treating disorders of carbohydrate metabolism.