Inhibition of p66Shc by Camellia sinensis Flavanols: A Potential Strategy Against Oxidative Stress in Alzheimer’s Disease

Reactive oxygen species (ROS) play essential roles in cellular processes, including immune defense and cell signaling. However, overproduction of the p66Shc protein leads to increased ROS levels and oxidative stress, greatly contributing to the progression of Alzheimer’s disease (AD). This study investigated the inhibitory potential effects of flavanols from the Camellia sinensis plant on p66Shc to reduce ROS generation. These flavanols examined included catechin, epicatechin gallate (ECG), epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), epigallocatechin (EGC), epicatechin (EC), and gallocatechin (GC). A homology model of p66Shc was constructed, and molecular docking simulations were performed to explore the flavanols and p66Shc interactions. One-way analysis of variance testing showed significant differences in binding affinities, and GCG had the strongest interaction (−7.6 kcal/mol) via van der Waals interactions. ECG and EGCG followed (−6.9 kcal/mol) and formed additional pi–anion and pi–alkyl interactions. Catechin had a binding score of −6.4 kcal/mol, while the remaining flavanols had a score of −6.2 kcal/mol with varied interactions. These findings suggested that GCG, ECG, and EGCG could be explored further for their potential role in mitigating oxidative stress in AD.