Synthesis, cytotoxicity and liver targeting of 3-O-β-D-Galactosylated Resveratrol.

Resveratrol (Res), a naturally occurring polyphenol, has shown pharmacological activities in treatment of liver diseases. However, the application of Res was limited by its poor bioavailability and liver targeting. Herein, 3-O-β-D-Galactosylated Resveratrol (Gal-Res) was synthesized by structural modification of Res to enhance bioavailability and liver targeting. The Gal-Res was characterized by IR, 1 H-NMR spectra and MS. The in vitro antitumour experiments, in vivo pharmacokinetics and biodistribution studies were evaluated. Gal-Res was successfully synthesized in our study. Compared to Res, Gal-Res resulted in enhanced cytotoxicity in HepG2 cells. After intravenous injection of normal SD rats, Gal-Res significantly improved the bioavailability of Res and the Cmax and AUC0-t of Gal-Res were 3.186 and 3.929 time than that of Res. In addition, in the study of liver targeting, the relative uptake rate (Re ) of Gal-Res in the liver (2.006) is the largest. The drug targeting efficiency (Te ; 38.924%) of Gal-Res was greater than that of Res. These showed that Gal-Res could significantly improve the distribution ability of Res in liver. On the whole, Gal-Res increased cellular uptake to HepG2 cells, bioavailability and liver targeting, providing its future clinical application in the treatment of liver diseases.