Acetylcholinesterase inhibitors from Corydalis yanhusuo

Abstract

In a bioassay-guided search for acetylcholinesterase (AChE) inhibitors from Chinese natural resources, eight isoquinoline alkaloids, tetrahydropalmatine (1), corydaline (2), protopine (3), berberine (4), palmatine (5), jatrorrhizine (6), coptisine (7) and dehydrocorydaline (8), were isolated from the methanolic extract of the tubers of Corydalis yanhusuo. Structures of these compounds were identified by spectroscopic techniques. Compounds 4–8 inhibited AChE activity in a dose-dependent manner, and the IC₅₀ values were 0.47 ± 0.01, 0.74 ± 0.06, 2.08 ± 0.09, 1.01 ± 0.03 and 0.62 ± 0.05 µM, respectively. Structure–activity relationship analysis suggested that aromatisation at ring C, as well as substitutions at C-2, C-3, C-9, C-10 and C-13 affect the AChE activity of protoberberine alkaloids.

Keywords:

• Corydalis yanhusuo; acetylcholinesterase
• isoquinoline alkaloids

Acknowledgements

This work was supported by grants from the Natural Science Foundation of Guizhou Province (Grant Nos. 20052068 and 20033048), and the Special Fund for Excellent Scholars in Education, Science and Technology of the Guizhou Provincial Governor.