Serum albumin complexed with ellagic acid from pomegranate peel and its metabolite urolithin B

As one of fruit waste by-products, the pomegranate peel is rich in bioactive compounds such as ellagic acid. Ellagic acid and its main gut microbial metabolite urolithin B have been reported to exhibit numerous biological activities and widely used as dietary supplements in the past decades. Interaction of these two compounds to serum albumin (SA) might affect their metabolism, efficacy, and body distribution. The interaction of ellagic acid and urolithin B with SA was investigated and BSA interference on the anti-cancer activity of these two compounds was also evaluated. Results of spectra experiments showed that ellagic acid and urolithin B could form complexes with bovine serum albumin (BSA) and urolithin B has a higher binding force and number of binding sites than ellagic acid when forming a complex with BSA. The results of molecular docking and molecular dynamics simulations suggested that ellagic acid and urolithin B tended to bind in site I rather than site II. The MTT assay results indicated that the IC50 value of ellagic acid decreased from 123.58 μM to 55.91 μM, while the IC50 value of urolithin B decreased from 83.67 μM to 47.40 μM. Ellagic acid and urolithin B can form complexes with serum albumin and the anti-cancer activity of ellagic acid and urolithin B was enhanced when combined with BSA. [Display omitted] Ellagic acid and urolithin B could bind to BSA and quench its intrinsic fluorescence.The results of computer simulations suggested that these two compounds tended to bind in site I of HSA.The anti-cancer activities of these two compounds were enhanced when combined with BSA.