Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids.
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 beta-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 IC(50) values ranging between 0.44-1.07 microM for AChE and 3.32-6.84 microM for BChE; only epiberberine (K(i)=10.0) and groenlandicine (K(i)=21.2) exerted good, non-competitive BACE1 inhibitory activities with IC(50) values of 8.55 and 19.68 microM, respectively. In two antioxidant assays, jateorrhizine and groenlandicine exhibited significant ONOO(-) scavenging activities with IC(50) values of 0.78 and 0.84 microM, respectively; coptisine and groenlandicine exhibited moderate total ROS inhibitory activities with IC(50) values of 48.93 and 51.78 microM, 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 beta-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 beta-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.
Jung
Hyun Ah
HA
Division of Food Science and Biotechnology, Pukyong National University, Busan, South Korea.
Min
Byung-Sun
BS
Yokozawa
Takako
T
Lee
Je-Hyun
JH
Kim
Yeong Shik
YS
Choi
Jae Sue
JS
D000110:Acetylcholinesterase / Q000378:metabolism; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D002091:Butyrylcholinesterase / Q000378:metabolism; D039323:Coptis / Q000737:chemistry; D000089042:Coptis chinensis; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism; D013053:Spectrophotometry; D013379:Substrate Specificity
D000470:Alkaloids; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; C107393:Coptidis rhizoma extract; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases