β-secretase (BACE1) inhibitors from sanguisorbae radix

In the course of screening anti-dementia agents from natural products, two β-secretase (BACE1) inhibitors were isolated from the ethyl acetate soluble fraction of Sanguisorbae Radix by the activity-guided purification using silica gel, Sephadex LH-20, and RP-HPLC. They were identified as 1,2,3-trigalloyl-4,6- hexahydroxydiphenoyl-β-D-glucopyranoside (Tellimagrandin II, 1) and 1,2,3,4,6-pentagalloyl-β-D-glucopyranoside (2) and were shown to non-competitively inhibit β-secretase (BACE1) with the IC ₅₀ values of 3.10×10 ^-6 M and 3.76×10 ^-6 M, respectively. The Ki values of 1 and 2 were 6.84×10 ^-6 M and 5.13×10 ^-6 M. They were less inhibitory to α-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.