β-Secretase (BACE1) inhibitors from Sanguisorbae Radix
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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 IC50 values of 3.10×10−6 M and 3.76×10−6 M, respectively. TheKi values of1 and2 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.
Key wordsβ-Secretase (BACE1) Inhibitor Sanguisorbae Radix Tellimagrandin II 1,2,3,4,6-Pentagalloyl-β-d-glucopyranoside Alzheimer's disease
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