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
