Synthesis of novel EGCG-glucose conjugates and studies of their antioxidative properties for neuroprotections

Epigallocatechin-3-gallate (EGCG) is a polyphenol naturally sourced in green tea with extensive bioactivities, including antioxidant, anti-carcinogenic, anti-microbial, anti-obesity, and neuroprotection. However, EGCG is unstable in neutral or alkaline conditions and has poor lipid solubility, leading to inadequate systemic absorption, reduced pharmacokinetics, limited biodistribution, and first-pass metabolism. The aim of this study is to solve these problems, thus two novel EGCG-glucose conjugates, Glu-EGCG and 2Glu-EGCG possessing one and two glucose, respectively, were designed, synthesized, and characterized. The EGCG-glucose conjugates’ chemical stability, cytotoxicity and alleviation H2O2-induced antioxidative damage to neuronal cell and antioxidative neuroprotection activities were examined. Compared with their precursor EGCG, Glu-EGCG and 2Glu-EGCG are more stable, less toxic to PC12 and bEnd.3 cell, stronger ability to attenuate H2O2-induced injury to PC12 cells resulting higher cell viability and lower reactive oxygen species (ROS) in the cell. Animal study results further proved that Glu-EGCG and 2Glu-EGCG possess higher antioxidative activities than EGCG, through decreasing the ischemia area, inhibiting morphological changes and neuronal loss in brain tissues, and modulating the oxidative factor and antioxidant factor. In conclusion, 2Glu-EGCG shows stronger antioxidant activities than Glu-EGCG does. Both EGCG-glucose conjugates are promising brain target antioxidative neuroprotection agents.