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

OBJECTIVES

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.

METHODS

The Gal-Res was characterized by IR, H-NMR spectra and MS. The in vitro antitumour experiments, in vivo pharmacokinetics and biodistribution studies were evaluated.

RESULTS

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 C and AUC 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 (R ) of Gal-Res in the liver (2.006) is the largest. The drug targeting efficiency (T ; 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.

CONCLUSIONS

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.