Green tea catechins as a BACE1 (β-Secretase) inhibitor

In the course of searching for BACE1 (β-secretase) inhibitors from natural products, the ethyl acetate soluble fraction of green tea, which was suspected to be rich in catechin content, showed potent inhibitory activity. (−)-Epigallocatechin gallate, (−)-epicatechin gallate, and (−)-gallocatechin gallate were isolated with IC50 values of 1.6×10−6, 4.5×10−6, and 1.8×10−6 M, respectively. Seven additional authentic catechins were tested for a fundamental structure–activity relationship. (−)-Catechin gallate, (−)-gallocatechin, and (−)-epigallocatechin significantly inhibited BACE1 activity with IC50 values of 6.0×10−6, 2.5×10−6, and 2.4×10−6 M, respectively. However, (+)-catechin, (−)-catechin, (+)-epicatechin, and (−)-epicatechin exhibited about ten times less inhibitory activity. The stronger activity seemed to be related to the pyrogallol moiety on C-2 and/or C-3 of catechin skeleton, while the stereochemistry of C-2 and C-3 did not have an effect on the inhibitory activity. The active catechins inhibited BACE1 activity in a non-competitive manner with a substrate in Dixon plots.