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Cryptotanshinone, an acetylcholinesterase inhibitor from Salvia miltiorrhiza, ameliorates scopolamine-induced amnesia in Morris water maze task.

Abstract
Alzheimer's disease (AD) is a common form of dementia which is characterized by the deposition of amyloids in affected neurons and a cholinergic neurotransmission deficit in the brain. The current therapeutic intervention for AD is primarily based on the inhibition of brain acetylcholinesterase (AChE) to restore the brain acetylcholine level. Cryptotanshinone (CT) is a diterpene extracted from the root of Salvia miltiorrhiza, a herb that is commonly prescribed in Chinese medicine to treat cardiovascular disease. In the present study, we demonstrated that CT is an inhibitor of both human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC(50) values of 4.09 and 6.38 microM, respectively. The IC(50) ratio of CT for BuChE:AChE was 1.56. CT inhibited human AChE in a reversible manner, and the inhibition showed the characteristics of mixed-type as both the KM and V(max) were affected by CT. The effect of CT on learning impairment in scopolamine-treated rats was also evaluated by the acquisition protocol of the Morris water maze. The task learning ability of scopolamine-treated rats was significantly reversed by CT (5 mg/kg), and the CT-fed rats were able to develop a spatial searching strategy comparable to that of the control animals. In addition, chronic CT treatment did not cause hepatotoxicity as measured by blood alanine transferase (ALT) level. Our findings demonstrate the ability of CT to improve task learning in rats with scopolamine-induced cognitive impairment. These results suggest that CT has the potential as a therapeutic drug for treating AD.
AuthorsKelvin Kin-Kwan Wong, Michelle Tsz-Wan Ho, Huang Quan Lin, Kwok-Fai Lau, John A Rudd, Ronald Chi-Kit Chung, Kwok-Pui Fung, Pang-Chui Shaw, David Chi-Cheong Wan
JournalPlanta medica (Planta Med) Vol. 76 Issue 3 Pg. 228-34 (Feb 2010) ISSN: 1439-0221 [Electronic] Germany
PMID19774505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightGeorg Thieme Verlag KG Stuttgart-New York.
Chemical References
  • Cholinesterase Inhibitors
  • Phenanthrenes
  • Plant Extracts
  • cryptotanshinone
  • Scopolamine
  • Acetylcholinesterase
  • Butyrylcholinesterase
Topics
  • Acetylcholinesterase (metabolism)
  • Alzheimer Disease (drug therapy)
  • Amnesia (chemically induced, drug therapy, metabolism)
  • Animals
  • Butyrylcholinesterase (metabolism)
  • Cholinesterase Inhibitors (isolation & purification, pharmacology, therapeutic use)
  • Humans
  • Male
  • Maze Learning (drug effects)
  • Phenanthrenes (isolation & purification, pharmacology, therapeutic use)
  • Phytotherapy
  • Plant Extracts (chemistry, pharmacology, therapeutic use)
  • Plant Roots
  • Rats
  • Rats, Sprague-Dawley
  • Salvia miltiorrhiza (chemistry)
  • Scopolamine

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