Inhibitors of Acetylcholine Esterase in vitro - Screening of Steroidal Alkaloids from Fritillaria Species

Abstract

18 alkaloids were successfully isolated from five Fritillaria species and 5 derivatives were synthesized. Their effects on the bioactivity of human whole blood cholinesterase (ChE) were assessed. The results showed that N-demethylpuqietinone, hupeheninoside, ebeiedinone, yibeinoside A and chuanbeinone inhibited the bioactivity of human whole blood ChE at the concentration of 1.0 × 10 ^{- 4} M, with the inhibitory effects of 55.5 ± 2.7 %, 66.8 ± 2.0 %, 69.0 ± 1.7 %, 71.2 ± 1.8 % and 70.7 ± 3.3 %, respectively. The effects of the five alkaloids on human red blood cell (RBC) acetylcholinesterase (AChE) and human plasma butyrylcholinesterase (BChE) were further studied, and their IC₅₀ values for human RBC AChE were 6.4 ± 0.003 μM, 16.9 ± 0.018 μM, 5.7 ± 0.004 μM, 6.5 ± 0.013 μM and 7.7 ± 0.001 μM, respectively, and the IC₅₀ values for human plasma BChE were 12.5 ± 0.026 μM, 2.1 ± 0.005 μM, 5.2 ± 0.002 μM, 7.3 ± 0.005 μM and 0.7 ± 0.001 μM, respectively. These data suggest, therefore, that N-demethylpuqietinone, hupeheninoside, ebeiedinone, yibeinoside A and chuanbeinone have both anti-RBC AChE and anti-plasma BChE activities, N-demethylpuqietinone is a selective inhibitor of AChE, whereas hupeheninoside and chuanbeinone are the selective inhibitors of BChE.

Abbreviations

AChE:acetylcholinesterase

AD:Alzheimer’s disease

BChE:butyrylcholinesterase

ChE:cholinesterase

ODN:optical density

RBC:red blood cell

Fritillaria - Lilliaceae - steroidal alkaloids - anti-cholinesterase - acetylcholinesterase - butyrylcholinesterase

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