Chemical characterization and urate-related activities of constituents of Paeonia lactiflora: 1,2,3,4,6-O-pentagalloylglucose inhibits xanthine oxidase and paeoniflorin modulates urate transporter expression in HK-2 cells.
TL;DR
Findings identify PGG and PF as two representative constituents of P. lactiflora with distinct urate-related activity profiles in enzymatic and cellular models, respectively.
Abstract
Hyperuricemia (HUA), a metabolic disorder associated with gout and cardiometabolic diseases, has become an important target for the development of food-derived functional ingredients. Paeonia lactiflora Pall, a widely consumed edible medicinal plant, has attracted attention as a potential source of urate-modulating compounds; however, its key active compounds and their urate-related activities remain unclear. In this study, through comprehensive phytochemical profiling, 20 compounds were isolated from P. lactiflora and systematically evaluated using xanthine oxidase (XO) inhibition and HK-2 cellular models. Among them, 1,2,3,4,6-O-pentagalloylglucose (PGG, 20) exhibited potent XO inhibitory activity, with an IC50 value of 8.11 μM. Molecular docking and 100 ns molecular dynamics simulations further supported the stable binding of PGG to the catalytic pocket of XO, suggesting its role in inhibiting UA production at the enzymatic level. To investigate the urate transport-related activity of the isolates, a UA-induced injury model was established in HK-2 cells. Paeoniflorin (PF, 1) showed the strongest protective effect, improving cell viability by 13.47%. Western blot analysis showed that PF modulated the expression of urate transport-related proteins in HK-2 cells by decreasing the levels of the reabsorption-associated transporters URAT1 and GLUT9 and increasing the levels of the secretion-associated transporters OAT1 and ABCG2. In conclusion, these findings identify PGG and PF as two representative constituents of P. lactiflora with distinct urate-related activity profiles in enzymatic and cellular models, respectively. This study provides a chemical and preliminary functional basis for the future development and quality evaluation of P. lactiflora-derived functional ingredients targeting urate metabolism.