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Novel diterpenoid
acetylcholinesterase inhibitors from Salvia
miltiorhiza.
Ren Y, Houghton PJ, Hider RC, Howes
MJ.
Department of Pharmacy, King's College London,
U.K.
Acetylcholinesterase (AChE, EC 3.1.1.7) inhibitors are the
only registered drugs used to treat Alzheimer's disease (AD). New AChE
inhibitors may contribute to the design of new pharmaceuticals and
supply information which will facilitate the understanding of the
interaction between inhibitors and the enzyme. The dried root of Salvia
miltiorhiza is called 'Danshen' in China, and has been used for the
treatment of cerebrovascular disease and CNS deterioration in old age
for over one thousand years. In this work, a modified Ellman method was
used to guide the fractionation of the active AChE inhibitory compounds
from an acetone extract. Four inhibitory compounds, dihydrotanshinone,
cryptotanshinone, tanshinone I and tanshinone IIA were isolated, and the
structures were identified by comparison of their spectral
characteristics with previous reports. The inhibitory activities of
dihydrotanshinone and cryptotanshinone were dose-dependent, their IC
(50) values being 1.0 microM and 7.0 microM, respectively. These two
compounds were the major inhibitory compounds in the extract as judged
by HPLC analysis, forming 0.054 % w/w and 0.23 % w/w in the dried root,
respectively, and in mixture they appear to be less active than as
isolated compounds. The clogP values of dihydrotanshinone,
cryptotanshinone, tanshinone I and tanshinone IIA were calculated as
2.4, 3.4, 4.8 and 5.8, respectively, which indicate that these compounds
have potential to penetrate the blood-brain barrier. This is the first
example of diterpenoids as inhibitors of AChE.
PMID: 15114495
[PubMed - indexed for MEDLINE]
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