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.

Evaluation of Coptidis Rhizoma–Euodiae Fructus couple and Zuojin products based on HPLC fingerprint chromatogram and simultaneous determination of main bioactive constituents

“…Furthermore, Peaks 6, 8, 9, 10, 11, 12, and 13 were identified as jatrorrhizine, epiberberine, coptisine, palmatine, berberine, evodiamine, and rutaecarpine, respectively, by comparing with the UV spectra and retention time of sample peaks to the corresponding chemical references under the same condition. Peak 11 (berberine), which is one of the greatest response and important active constituents (Jang et al, 2009;Jung et al, 2008;Yan et al, 2008) in these samples, was chosen to calculate the relative retention time (RRT) and relative peak area (RPA). RRT and RPA of characteristic peaks in 10 samples are shown in Table 2.…”

Berberine ameliorates hyperglycemia in alloxan-induced diabetic C57BL/6 mice through activation of Akt signaling pathway

“…1), one of the main constituents of Coptidis rhizoma and Cortex phellodendri, is an isoquinoline alkaloid with multiple pharmacological activities. BBR has exhibited hypoglycemic, hypolipidemic, anti-oxidation, antitumor and anti-aldose reductase effect, which presents wide clinical values and perspectives in treating diabetes and its complications [13][14][15][16][17][18]. Our previous studies demonstrated that BBR could efficiently ameliorate hyperglycaemia in streptozotocin-induced diabetic rats [19,20].…”

Chemical Constituents from Thalictrum ramosum

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Compound 1 was obtained by recrystallization of Fr.…”