Dual Strategy for Improving the Oral Bioavailability of Resveratrol: Enhancing Water Solubility and Inhibiting Glucuronidation

Resveratrol (RES) suffers from poor water solubility and extensive metabolism, which lead to low bioavailability. A phospholipid complex (PC) containing RES and a UDP-glucuronosyltransferase (UGT) inhibitor was prepared to address these two limiting factors, thereby improving RES bioavailability. First, 11 natural active ingredients metabolized by similar enzyme subtypes to RES were screened in a glucuronidation assay in liver microsomes. Then, glycyrrhetinic acid (GA), the strongest inhibitor, was prepared with RES in a PC. RES-PC was prepared as a control. As expected, the water solubility and the cumulative dissolution of RES were significantly enhanced by RES-PC and RES/GA-PC. Compared with the RES group, the AUC_0–10 of RES and resveratrol-3-glucuronide (R-3-G) in the RES/GA-PC group showed increases of 2.49- and 1.70-fold, respectively, with the proportion of RES absorption to total absorption increasing 1.45 times. These results demonstrated that RES/GA-PC could improve the bioavailability of RES by increasing its water solubility and inhibiting its glucuronidation.