Study On Anti-Alzheimer’s Disease Of Amaryllidaceous Alkaloids Based On A System-level Approach

Amaryllidaceae plants are abundant in alkaloids. Amaryllidaceae alkaloids are structurally diverse and possess various pharmacological effects, much attention has been paid to Amaryllidaceae alkaloids, especially effect on Alzheimer’s disease. But few studies focus on screening and evaluating the active ingredients of Amaryllidaceae alkaloids and elucidating the mechanism of Amaryllidaceae alkaloids against Alzheimer’s disease systematically. In this study, systems pharmacology was established to investigate the mechanism of action for Amaryllidaceae alkaloids in treatment of Alzheimer’s disease by integrating active component screening, drug-likeness evaluation, target prediction and validation, and network analysis. Mordern chromatography separation technology was applied to separate and purificate alkaloid compounds from bulbs of lycoris radiata, and the structures of these compounds were elucidated according to their physical and chemical properties and spectral data. The methods and results of this study provided a scientific basis for further development of new drug from Amaryllidaceae alkaloids with functions of Alzheimer’s disease prevention and treatment and provided a new idea for study of the activity of natural active componds and development of new drugs possessing specific pharmacological activity.A total of 100 active components(28%) were selected from 357 known Amaryllidaceae alkaloids. Tazettine-type and homolycorine-type alkaloids showed best activity, galantamine-type, lycorine-type and crinine-type alkaloids exhibited good activity. 39 Alzheimer’s disease-related targets were obtained from the active components, including 25 therapeutic targets that has been validated for treatment of Alzheimer’s disease and 14 predicted targets which are associated with Alzheimer’s disease. The results of compound–target and target–pathway networks displayed that Amaryllidaceae alkaloids exert anti-Alzheimer’s disease effects by directly regulating the calcium signaling pathway and other 11 signaling pathways. This study applied a variety of chromatographic separation technology isolated 6 compounds and identified the structures of them by modern spectrum technology. 2 lycorine-type alkaloids: lycorine(compound 1) and zephyranthine(compound 6); 3 homolycorine-type alkaloids: homolycorine(compound 2), hippeastrine(compound 3) and 9-O-demethylhomolycorine(compound 4); 1 galantamine-type alkaloid: lycoramine(compound 5) were identified by nuclear magnetic resonance spectrum.This study applied systems pharmacology method, evaluated bioactivity of Amaryllidaceae alkaloids, explored the pharmacological mechanism for Amaryllidaceae alkaloids in treatment of Alzheimer’s disease, separated and identified several different types of alkaloid compounds through the modern chromatographic and spectroscopic techniques. Ultimately, the results provided reliable theoretical basis and research foundation for further development and utilization of Amaryllidaceae alkaloids and new ideas for the development of novel drugs.