β-Secretase (BACE1) inhibitors from Sanguisorbae Radix

Abstract

In the course of screening anti-dementia agents from natural products, two beta-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-beta-D-glucopyranoside (Tellimagrandin II, 1) and 1,2,3,4,6-pentagalloyl-beta-D-glucopyranoside (2) and were shown to non-competitively inhibit beta-secretase (BACE1) with the IC50 values of 3.10x10(-6) M and 3.76x10(-6) M, respectively. The Ki values of 1 and 2 were 6.84x10(-6) M and 5.13x10(-6) M. They were less inhibitory to alphasecretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.

Natural products as a source of Alzheimer's drug leads

“…longifolia (Bertol.) T.T.Yu & C.L.Li.. 188 Finally, weak (>100 μM) furanocoumarin inhibitors of BACE1 were reported from the roots of Angelica dahurica L. (Apiaceae) and phlorotannin inhibitors were reported from the marine kelp Eisenia bicyclis Setchell (Lessoniaceae) with low micromolar potency. 189 …”

Screening of acetylcholinesterase inhibitors in herbal medicines

“…Among of 8 herbal medicines which showed more than 50 % of AChE inhibitory activities, Uncariae Ramulus et Uncus was known to ameliorate learning and memory deficits partly through neuroprotective effects on the central acetylcholine system (Kim et al 2004). And loganin, one of the major components of Longanae Flos, reversed scopolamine-induced learning and memory impairments and significantly inhibited acetylcholinesterase activity (Lee et al 2005). Eccrine sweat glands are innervated by postganglionic sympathetic fibers.…”

BACE1 inhibitory activity of fungal endophytic extracts from Malaysian medicinal plants

“…Chitosan derivatives from crab shell and latifolin from Dalbergia sissoo have shown weak BACE1 inhibition [34,35]. Catechins from green tea [13], ellagic acid and punicalagin from pomegranate [36], hispidin from mycelial cultures of Phellinus linteus [37] and several compounds isolated from Sanguisorbae radix [38] have all been studied as BACE1 inhibitors. In order to have therapeutic potential, however efficacious penetration of the blood-brain barrier requires the molecular weights of inhibitors to be under 700 Da making large peptide-based inhibitors unsuitable as drug candidates.…”