Effect of phenolic compounds from the rind of Punica granatum on the activity of three metabolism-related enzymes

Enzyme activity modulation by synthetic compounds provide strategies combining the inhibitory and therapeutic mode of action of the confirmed inhibitors. However, natural modulators could offer a valuable alternative for synthetic ones for the treatment of different chronic diseases (diabetes, hypertension, cancer) due to the numerous side effects of the latter. In vitro screening assays were conducted for Punica granatum rind methanolic extract against three metabolism-related enzymes: alpha-amylase, tyrosinase, and hyaluronidase. The obtained results showed that the examined extract retained high multitarget inhibition with inhibition percentages 31.5 +/- 1.3%, 75.9 +/- 4.7%, and 68.5 +/- 5.3% against alpha-amylase, tyrosinase, and hyaluronidase, respectively. Bioguided fractionation of P. granatum rind extract revealed that quercetin is the major active compound with inhibitory activities: 54.3 +/- 2.7%, 94.2 +/- 3.5%, and 90.9 +/- 2.7% against alpha-amylase, tyrosinase, and hyaluronidase, respectively. Kinetic studies of enzymes showed that quercetin inhibition was noncompetitive, uncompetitive, and competitive for alpha-amylase, tyrosinase, and hyaluronidase, respectively. The molecular docking of quercetin with alpha-amylase and hyaluronidase showed high binding energy with different bonds stabilizing the ligand-protein complex. Compiling all obtained results led to conclude that both P. granatum rind extract and quercetin have multitarget activities with potential therapeutic applications in many metabolic disorders.