An emerging flavone glycoside from Phyllanthus emblica L.: A promiscuous enzyme inhibitor and potential therapeutic in chronic diseases

Abstract

Nowadays, the designing of a single drug molecule interacting simultaneously and specifically with multiple targets (exhibits compound promiscuity) is gaining major consideration in drug discovery. Our previous screening research of 54 medicinal plants for possible multi-target inhibitory activity revealed that the methanolic extract of Phylanthus emblica L. leaves exhibited promising inhibitory activity with 98.37 ±1.09, 52.84±1.39, and 86.90±0.27 % against alpha amylase, tyrosinase, and hyaluronidase enzymes, respectively. Subsequently, bioassay-guided fractionation revealed that ethyl acetate fraction retained the highest inhibitory activity against all the three tested enzymes with 99.72±1.79, 59.09±1.93, and 87.36±0.48 %, respectively. Further fractionation of ethyl acetate fraction resulted in the isolation of two flavone glycosides; luteolin-7-O-α-L-rhamnoside (1) and apigenin-7-O-α-L-rhamnoside (2). Compound 1 exhibited strong inhibitory activity with 89.79, 41.50, and 67.25% against alpha amylase, tyrosinase, and hyaluronidase, respectively. Kinetics studies and molecular docking simulation revealed and confirmed that compound 1 is a non-competitive inhibitor for both alpha amylase and tyrosinase but a competitive inhibitor for hyaluronidase. Outcome of this study suggests that luteolin-7-O-α-L-rhamnoside from Phyllanthus emblica L. could be used as a potential promiscuous enzyme inhibitor in the management and treatment of some chronic diseases.