Planta Med 2004; 70(3): 201-204
DOI: 10.1055/s-2004-815535
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Novel Diterpenoid Acetylcholinesterase Inhibitors from Salvia miltiorhiza

Yuhao Ren1 , Peter J. Houghton1 , Robert C. Hider1 , Melanie-Jayne R. Howes2
  • 1Department of Pharmacy, King’s College London, London, U.K.
  • 2Current address: Jodrell Laboratory, Royal Botanic Gardens Kew, Richmond, U.K.
Further Information

Publication History

Received: July 7, 2003

Accepted: December 6, 2003

Publication Date:
23 March 2004 (online)

Abstract

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 IC50 values being 1.0 μM and 7.0 μM, 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.

References

Prof. Peter Houghton

Department of Pharmacy

King’s College London

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Email: peter.houghton@kcl.ac.uk