LAUSR

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 Psidium guajava leaf methanolic extract against three metabolism‐related enzymes; α‐amylase, tyrosinase, and hyaluronidase. The obtained results showed that the examined extract retained weak and moderate multitarget inhibition against α‐amylase, tyrosinase, and hyaluronidase, respectively; however, the leaf fractions exhibited stronger inhibitions for the three investigated enzymes. Fractionation of P. guajava leaf extract revealed that anthraquinones and ellagic acid are of the major active compounds with inhibitory activities for α‐amylase, tyrosinase, and hyaluronidase. Kinetic studies showed that quinalizarin inhibition is competitive for both α‐amylase and hyaluronidase, and ellagic acid inhibition for tyrosinase and hyaluronidase is competitive and un‐competitive, respectively. The molecular docking studies of quinalizarin and ellagic acid with α‐amylase, tyrosinase, and hyaluronidase showed high binding energies with different bonds stabilizing the ligand–protein complex. Compiling all obtained results led to conclude that both P. guajava leaf fractions, quinalizarin and ellagic acid, have multitarget activities with potential therapeutic applications in many metabolic disorders.