title: Inhibitory activities of the alkaloids from Coptidis Rhizoma against aldose reductase.
abstract: As part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications, the rat lens aldose reductase (RLAR) inhibitory effect of Coptidis Rhizoma (the rhizome of Coptis chinensis Franch) was evaluated. Its extract and fractions exhibited broad and moderate RLAR inhibitory activities of 38.9 approximately 67.5 microg/mL. In an attempt to identify bioactive components, six quaternary protoberberine-type alkaloids (berberine, palmatine, jateorrhizine, epiberberine, coptisine, and groenlandicine) and one quaternary aporphine-type alkaloid (magnoflorine) were isolated from the most active n-BuOH fraction, and the chemical structures therein were elucidated on the basis of spectroscopic evidence and comparison with published data. The anti-diabetic complications capacities of seven C. chinensis-derived alkaloids were evaluated via RLAR and human recombinant AR (HRAR) inhibitory assays. Although berberine and palmatine were previously reported as prime contributors to AR inhibition, these two major components exhibited no AR inhibitory effects at a higher concentration of 50 microg/ml in the present study. Conversely, epiberberine, coptisine, and groenlandicine exhibited moderate inhibitory effects with IC(50) values of 100.1, 118.4, 140.1 microM for RLAR and 168.1, 187.3, 154.2 microM for HRAR. The results clearly indicated that the presence of the dioxymethylene group in the D ring and the oxidized form of the dioxymethylene group in the A ring were partly responsible for the AR inhibitory activities of protoberberine-type alkaloids. Therefore, Coptidis Rhizoma, and the alkaloids contained therein, would clearly have beneficial uses in the development of therapeutic and preventive agents for diabetic complications and diabetes mellitus.
authors.affiliation: Division of Food Science and Biotechnology, Pukyong National University, Busan 608-737, Korea.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
authors.forename: Na Young
authors.initials: NY
authors.lastname: Yoon
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Bae
authors.forename: Byung-Sun
authors.initials: BS
authors.lastname: Min
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007908:Lens, Crystalline / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D010936:Plant Extracts / Q000737:chemistry; D029626:Ranunculaceae / Q000737:chemistry*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011994:Recombinant Proteins; D000449:Aldehyde Reductase