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 μM for AChE and 3.32—6.84 μM for BChE; only epiberberine (Ki=10.0) and groenlandicine (Ki=21.2) exerted good, non-competitive BACE1 inhibitory activities with IC50 values of 8.55 and 19.68 μM, respectively. In two antioxidant assays, jateorrhizine and groenlandicine exhibited significant ONOO− scavenging activities with IC50 values of 0.78 and 0.84 μM, respectively; coptisine and groenlandicine exhibited moderate total ROS inhibitory activities with IC50 values of 48.93 and 51.78 μM, 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.
2009 The Pharmaceutical Society of Japan