Extracts and constituents of Leontopodium alpinum enhance cholinergic transmission: brain ACh increasing and memory improving properties.

Full Abstract

Leontopodium alpinum ('Edelweiss') was phytochemically investigated for constituents that might enhance cholinergic neurotransmission. The potency to increase synaptic availability of acetylcholine (ACh) in rat brain served as key property for the bioguided isolation of cholinergically active compounds using different chromatographic techniques. The dichlormethane (DCM) extract of the root, fractions and isolated constituents were injected i.c.v. and the effect on brain ACh was detected via the push-pull technique. The DCM extract enhanced extracellular ACh concentration in rat brain and inhibited acetylcholinesterase (AChE) in vitro. The extracellular level of brain ACh was significantly increased by the isolated sesquiterpenes, isocomene and 14-acetoxyisocomene, while silphiperfolene acetate and silphinene caused a small increasing tendency. Only silphiperfolene acetate showed in vitro AChE inhibitory activity, thus suggesting the other sesquiterpenes to stimulate cholinergic transmission by an alternative mechanism of action. Isocomene was further investigated with behavioural tasks in mice. It restored object recognition in scopolamine-impaired mice and showed nootropic effects in the T-maze alternation task in normal and scopolamine-treated mice. Additionally, this sesquiterpene reduced locomotor activity of untreated mice in the open field task, while the activity induced by scopolamine was abolished. The enhancement of synaptic availability of ACh, the promotion of alternation, and the amelioration of scopolamine-induced deficit are in accordance with a substance that amplifies cholinergic transmission. Whether the mechanism of action is inhibition of AChE or another pro-cholinergic property remains to be elucidated. Taken together, isocomene and related constituents of L. alpinum deserve further interest as potential antidementia agents in brain diseases associated with cholinergic deficits.

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Author information

Author/s: Hornick, Ariane (A); Schwaiger, Stefan (S); Rollinger, Judith M (JM); Vo, Nguyen Phung (NP); Prast, Helmut (H); Stuppner, Hermann (H);

Affiliation: Institute of Pharmacy, Pharmacology and Toxicology, University of Innsbruck, A-6020 Innsbruck, Austria.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Biochemical pharmacology (Biochem Pharmacol), published in England. (Language: eng)

Reference: 2008-Jul; vol 76 (issue 2) : pp 236-48

Dates: Created 2008/06/30; Completed 2008/07/31;

PMID: 18541221, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acetylcholinesterase - metabolism
Animals
Asteraceae - chemistry
Behavior, Animal - drug effects
Brain - drug effects; physiology
Cholinesterase Inhibitors - pharmacology
Female
Galantamine - pharmacology
Memory - drug effects

Mice
Mice, Inbred C57BL
Motor Activity - drug effects
Plant Extracts - pharmacology
Plant Roots - chemistry
Rats
Rats, Sprague-Dawley
Sesquiterpenes - pharmacology
Tacrine - pharmacology

Associated Chemicals: Cholinesterase Inhibitors (0) ; Plant Extracts (0) ; Sesquiterpenes (0) ; Tacrine (321-64-2) ; Galantamine (357-70-0) ; Acetylcholinesterase (EC 3.1.1.7)

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