Preparation, identification and potential mechanism of novel urate-lowering active peptide from hemp protein: From animal model to computer simulation.

Abstract

This study examined the xanthine oxidase (XO) inhibitory potential of hemp protein hydrolysates, prepared using various proteases. The hydrolysate derived from neutral protease showed the strongest XO inhibition (IC = 0.99 ± 0.31 mg/mL) and significantly reduced serum uric acid, creatinine, and urea nitrogen levels in hyperuricemia mice while enhancing renal histopathology. LC-MS/MS identified three novel XO-inhibitory peptides (AMRAMPDDVLAN, NNYNLPIL, KTNDNAWVSPLAG) with ICvalues ranging from 1.34 to 2.81 mM. Molecular docking and dynamics simulations revealed the binding mechanisms through interactions with key catalytic residues, such as Ser876, and the obstruction of the hydrophobic channel. These findings emphasize the hydrolysate and its bioactive peptides as promising candidates for controlling hyperuricemia.