Identification and Validation of Urea Transporter B Inhibitor from Apium graveolens L. Seeds In Vitro and In Silico

Celery (<i>Apium graveolens</i> L.) seeds are rich in carbohydrates and protein, and they are widely used in diuretic drugs among Uyghur doctors. However, the diuretic mechanism is still unclear. To explore the possible diuretic mechanism of celery seeds, urea transporters, a potential diuresis-related target, are used in this study. Urea transporters (UTs) play a key role of urine concentration. Selective knockout of UTs can concentrate urea without affecting water and electrolytes, resulting in selective diuresis, which is a promising new diuretic target. In the present study, we obtained different polar fractions by extracting and separating celery seed extract, characterized its polar fractions using UPLC-TOF-MS, and verified its action using an erythrocyte lysis model in vitro. Then, it was found that the isovaleric acid <i>p</i>-tolylester exhibited moderate activity (IC₅₀ = 80.34 μM). Finally, its inhibitory effect on UT-B was investigated by using molecular docking, a pharmacophore model, and molecular dynamics simulations. This study provides a new approach to developing novel diuretics.