In silico identification and experimental validation of diuresis compounds from Euphorbia lathyris for potential UT-B inhibitors

Euphorbia lathyris ( E. lathyris ), a traditional Chinese medicine, rich in diterpenoids, has been widely used for the treatment of hydropsy, especially the ascites in China, with its mechanism is still unclear. For exploring possible diuresis mechanism of E. lathyris , in this study, a potential diuresis related target, urea transporter B (UT-B), and its potential ligands were discovered by using bioinformatics method of “Inverse Docking”. Then, homology modeling, molecular docking and ligand-based pharmacophore methods were applied to research the possible mechanism of diuresis. Bioinformatics analysis showed that most of diterpenoids in E. lathyris were optimal ligands for the UT-B protein and these predicted compounds also exhibited stable affinity to UT-B binding site, a hydrophobic region in urea passage. The HPLC-TOF-MS method was used to characterize the main diterpenoids content of E. lathyris extracts and three out of eight proposed diterpenoids were detected and assigned. In vitro UT-B inhibition experiment of erythrocyte lysis assay was then applied to confirm the diuretic effects of the diterpenoids concentrated extracts of E. lathyris . The half erythrocyte lysis rate of 23.89 µg/ml of diterpenoids concentrated extracts showed moderate UT-B inhibition efficacy. All these performances might also raise an alternative approach for the design of new diuretic drugs.