Interations Mechanism Between Epigallocatechin-3-Gallate (EGCG) Analogs And Amylase ? Protein (A?) And ?-Amylase

It has been reported that Epigallocatechin-3-gallate (EGCG) analogs show activities against Alzheimer's disease and obesity. However, the molecular interaction mechanisms between EGCG with Amyloid ? protein (AP) and ?-Amylase associated with the above mentioned diseases are not fully understood so far. To meet this challenge, we are elucidating the effects of EGCG structural analogs on the protein activity, conformation, thermostability of A? and ?-Amylase properties at the molecular level and individual immunology at the tissue level. Major research achievements are:1. The interaction molecular mechanism between EGCG analogs and A?42 at the molecular level is investigated by means of Thioflavin T fluorescence (ThT), circular dichroism (CD), atomic force microscopy (AFM), and differential scanning calorimetry (DSC). Results show that EGCG analogs could inhibit A?42 aggregation as well as remodel A?42 mature fibers depending on EGCG structure and concentration. Based on structure-activity relationship, the inhibitory effects of EGCGs were decreasing by EGCG> GCG> ECG> EGC. The contribution efficiency against A042 fibrillation for the groups in EGCG chemical structure decreased by the order of galloyl moiety >3'-hydroxyl group> epimer.2. The interaction mechanism between EGCG and ?-Amylase is studied at variant levels of thermodynamic, kinetic and protein conformation. The results show that EGCG reduces the thermal enthalpy and stability of ?-Amylase. EGCG presents a noncompetitive inhibitor on ?-Amylase activity. EGCG shows a dynamic fluorescence quenching from fluorescence quenching analysis. EGCG affects protein conformation, especially the contents of a helix element. EGCG changes amylase aggregate manner leading to decrease the water hydraulic radius of the protein aggregate.3. Animal experiments show that EGCG has a positive effect and treatment against Alzheimer and obesity deseases from the results of tissue immunology and enzyme activities measurement. Feeding AD mice with EGCG for 30 days, EGCG can improve abnormal enzyme activities of AchE and ChAT in serum and reduce the damage caused by oxidative stress injury on the hippocampus and cerebral cortex. Protein immunology images indicated that EGCG could inhibit the over-expression and accumulate of A?42 protein in the hippocampus of AD mice. Furthermore, obesity mice treated with EGCG showed decreasing body weight by 37.93% in comparison with the controls. Pathological tissue analyses show that the adipocyte cross-sectional area of EGCG treated mice is reduced by 54.8% in comparison with the untreated ones, as well as vacuolation and adipose infiltration in liver tissue are obviously improved in cases of EGCG treated groups.