Anti-Alzheimer and antioxidant activities of coptidis rhizoma alkaloids

Abstract

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 Pharmaceutical Society of Japan.