Conjugation of catechins with cysteine generates antioxidant compounds with enhanced neuroprotective activity

Abstract

Antioxidant compounds derived from the conjugation of (−)-epicatechin and (−)-epicatechin 3-O-gallate with cysteine and cysteine derivatives protected HT-22 nerve cells (EC50 between 36 and 65 μM) from death triggered by glutamate while underivatized (−)-epicatechin was almost inactive (EC50 = 610 μM). Differences in free radical scavenging capacity (DPPH assay) could not account for the improvement in neuroprotective activity upon derivatization of (−)-epicatechin with thiols. Moreover, while the gallate-containing compounds are more efficient radical scavengers than their non-galloylated counterparts, they are only equally or less potent as neuroprotective agents. Although all of the conjugates were able to scavenge mitochondrially generated reactive oxygen species (ROS) inside the cells, the majority of their neuroprotective activity appeared to be dependent upon their ability to maintain glutathione levels. These results suggest that a mechanism other than ROS scavenging is involved in the neuroprotective action exerted by the epicatechin conjugates.