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

Abstract

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, 1H‐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 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. 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.

The Role of Resveratrol in Liver Disease: A Comprehensive Review from In Vitro to Clinical Trials

“…Resveratrol also reduced the pyrogallol-induced increase in the activity of the metabolizing enzymes CYP1A2 (cytochrome P450 1A2) and CYP2E1 (cytochrome P450 2E1) [137]. A recent study by Farghali et al [138] demonstrated that administration of resveratrol attenuated inflammation in d-galactosamine-sensitive and LPS-induced hepatitis [139]. This was highlighted by a reduction in TBARS (thiobarbituric acid reactive substances), AST, ALT, conjugated dienes, and bilirubin levels.…”

Galactose-Induced Skin Aging: The Role of Oxidative Stress

“…Aging models based on the administration of D-gal have been intensively utilized for validation of the antiaging efficacy of natural antioxidant compounds over the last decades [148]. In fact, the antioxidant properties of polyphenols have been tested in a number of studies using a model of skin aging based on the use of D-gal [149][150][151][152]. For instance, it was established that the combined treatment using resveratrol and calorie restriction restores hair condition, skin elasticity, and skin thickness in rats treated by D-gal [85].…”

Preparation, characterization and preliminary pharmacokinetic study of pH-sensitive Hydroxyapatite/Zein nano-drug delivery system for doxorubicin hydrochloride

“…Currently, anticancer drugs are limited by weak selectivity towards tumour cells and severe side effects on normal tissues . Nano‐drug delivery systems, such as polymeric micelles, liposomes and nanoparticles (NPs), have been used to increase tumour targeting .…”

“…Currently, anticancer drugs are limited by weak selectivity towards tumour cells and severe side effects on normal tissues. [1][2][3][4] Nano-drug delivery systems, such as polymeric micelles, liposomes and nanoparticles (NPs), have been used to increase tumour targeting. [5][6][7][8][9] NPs are known to enter tumour cells through the enhanced permeability and retention (EPR) effect due to their small size and large surface area.…”