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标题：Anti-Alzheimer and Antioxidant Activities of Coptidis Rhizoma Alkaloids
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作者：Hyun Ah Jung ; Byung-Sun Min ; Takako Yokozawa 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：8
页码：1433-1438
DOI：10.1248/bpb.32.1433
出版社：The Pharmaceutical Society of Japan
摘要：Coptidis Rhizoma and its isolated alkaloids are reported to possess a variety of activities, including neuroprotective and antioxidant effects. Thus, the anti-Alzheimer and antioxidant effects of six protoberberine alkaloids (berberine, palmatine, jateorrhizine, epiberberine, coptisine, and groenlandicine) and one aporphine alkaloid (magnoflorine) from Coptidis Rhizoma were evaluated via β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) assays, along with peroxynitrite (ONOO⁻) scavenging and total reactive oxygen species (ROS) inhibitory assays. Six protoberberine alkaloids exhibited predominant cholinesterases (ChEs) inhibitory effects with IC₅₀ values ranging between 0.44—1.07 μ M for AChE and 3.32—6.84 μ M for BChE; only epiberberine ( K _i=10.0) and groenlandicine ( K _i=21.2) exerted good, non-competitive BACE1 inhibitory activities with IC₅₀ values of 8.55 and 19.68 μ M , respectively. In two antioxidant assays, jateorrhizine and groenlandicine exhibited significant ONOO⁻ scavenging activities with IC₅₀ values of 0.78 and 0.84 μ M , respectively; coptisine and groenlandicine exhibited moderate total ROS inhibitory activities with IC₅₀ values of 48.93 and 51.78 μ M , respectively. These results indicate that Coptidis Rhizoma alkaloids have a strong potential of inhibition and prevention of Alzheimer's disease (AD) mainly through both ChEs and β-amyloids pathways, and additionally through antioxidant capacities. In particular, groenlandicine may be a promising anti-AD agent due to its potent inhibitory activity of both ChEs and β-amyloids formation, as well as marked ONOO⁻ scavenging and good ROS inhibitory capacities. As a result, Coptidis Rhizoma and the alkaloids contained therein would clearly have beneficial uses in the development of therapeutic and preventive agents for AD and oxidative stress-related disease.
关键词：protoberberine;cholinesterase;peroxynitrite;β-site amyloid precursor protein cleaving enzyme 1;Coptidis Rhizoma;total reactive oxygen species