Open AccessSynthesis, cytotoxicity and liver targeting of 3‐O‐β‐D‐Galactosylated Resveratrol
Author(s) -
Qian Jiajia,
Zha Liqiong,
Wang Beilei,
Zhang Caiyun,
Hong Lufeng,
Chen Weidong
Publication year - 2019
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13084
Subject(s) - bioavailability , resveratrol , cmax , pharmacology , pharmacokinetics , biodistribution , cytotoxicity , chemistry , in vivo , in vitro , distribution (mathematics) , medicine , biochemistry , biology , mathematical analysis , microbiology and biotechnology , mathematics
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, 1 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 max and AUC 0– 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 ( R e ) of Gal‐Res in the liver (2.006) is the largest. The drug targeting efficiency ( T e ; 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.