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Cotinus coggygria heartwood: a new source of acetylcholinesterase inhibiting compounds
Acetylcholinesterase (AChE) inhibition is today the main strategy in the clinical management of Alzheimer's disease. Its benefits extend from early stages of various dementia types into Parkinson's disease, ataxia, and myasthenia gravis1. Natural products have already established themselves as an excellent source for AChE inhibiting compounds (e.g. galantamine, huperzine A), but new substances with better efficacy and less side effects are still demanded2. While performing a screening of extracts from our plant collection using an enzyme assay with Ellman's reagent3, preparations made of sumac (Cotinus coggygria Scop., Anacardiaceae) were shown to inhibit AChE; the most potent was the methanol extract of the heartwood (IC50 of 89.3µg/ml; CI95 72.4–108.7µg/ml). Subsequent tests pointed to the ether partition as most active fraction of the above extract (IC50 of 25.4µg/ml; CI95% 20.8–32.2µg/ml). Bioactivity-guided isolation highlighted sulfuretin, its main component, as active compound (IC50 of 29.9µM; CI95% 26.4–33.7µM). Following these positive preliminary results, we investigated in vivo the ability of sumac extracts to enhance cholinergic transmission in the brain, using the push-pull technique. Injection into the ipsilateral cerebral ventricle of 10mg/kg ether partition increased the extracellular acetylcholine concentration in rat brain to about 220% compared to basal release. These are the first in vivo results demonstrating the elevation of cerebral acetylcholine level by an aurone-enriched C. coggygria fraction.
Acknowledgements: The authors wish to thank the Austrian Science Fund (FWF) for financial support (grant nr. P18379), Prof. Dr. Ernst Ellmerer (Institute of Organic Chemistry, University of Innsbruck) for NMR measurements and Barbara Bergner for technical assistance
References: 1. Lockhart, B.P., Lestage, P.J. (2003) Exp. Gerontology 38:119–128.
2. Houghton, P.J., Howes, M.-J. (2005) Neurosignals 14: 6–22.
3. Ellman, G.L. et al. (1961) Biochem Pharmac 7: 88–95.