sulfuretin and butein

Topics: Animals; Antioxidants; Apoptosis; Benzofurans; Caspase 3; Cell Survival; Chalcones; Ditiocarb; Flavonoids; Hydrogen Peroxide; Neurons; Oxidative Stress; PC12 Cells; Phenols; Plant Extracts; Rats; Rhus; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Superoxide Dismutase

It is becoming increasingly important to investigate drug metabolites to evaluate their toxic or preventive effects after administration of the parent compound. In our previous study, isoliquiritigenin isolated from Glycyrrhizae Radix effectively protected mouse-derived hippocampal neuronal cells (HT22) against 5mM glutamate-induced oxidative stress. However, there is little information on the protective effects of the metabolites of isoliquiritigenin on HT22 cells. In this study, isoliquiritigenin and its Phase I metabolites were prepared and their neuroprotective activities on glutamate-treated HT22 cells were compared. The prepared metabolites were liquiritigenin (1), 2',4,4',5'-tetrahydroxychalcone (2), sulfuretin (3), butein (4), davidigenin (5), and cis-6,4'-dihydroxyaurone (6). Among the six metabolites, 4 showed better neuroprotective effects than the parent compound, isoliquiritigenin. Our study suggests that the neuroprotective effect of isoliquiritigenin could be elevated by its active metabolite 4, which is a chalcone containing a catechol group in the B ring.

Topics: Animals; Benzofurans; Cell Death; Cell Line; Chalcone; Chalcones; Flavonoids; Glutamic Acid; Hippocampus; Mice; Neurons; Neuroprotective Agents

Rhus verniciflua stokes (RVS) is known to promote blood circulation by preventing blood stasis, although the active ingredients and the underlying mechanism are unclear. Platelets are the primary cells that regulate circulation and contribute to the development of diverse cardiovascular diseases by aggregation and thrombosis. The study assessed the antiplatelet activity of RVS and sought to identify the active constituents. Pretreatment of washed platelets with RVS heartwood extract blunted the aggregatory response of platelets to collagen. In the subfractions, fisetin, butein, and sulfuretin were identified as effective inhibitors of platelet aggregation by collagen, thrombin, and adenosine-5'-diphosphate. Antiplatelet activities of all three compounds were concentration dependent, and fisetin had longer in vitro duration of action compared with butein or sulfuretin. Extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase activation by collagen was prevented by fisetin, whereas butein and sulfuretin failed to inhibit ERK and p38 activation was not affected by any of the compounds. Rats orally administered 100 mg/(kg·day(-1)) fisetin for 7 days were resistant to arterial thrombosis, although total extract of RVS heartwood exhibited little effect at a dose of 1000 mg/(kg·day(-1)). RVS heartwood may have cardiovascular protective activity by inhibiting platelet aggregation. The active constituents are fisetin, butein, and sulfuretin, and fisetin is orally effective against thrombosis.

Topics: Animals; Benzofurans; Blood Platelets; Cardiovascular Diseases; Chalcones; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Flavonols; Male; p38 Mitogen-Activated Protein Kinases; Phytotherapy; Plant Extracts; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats, Sprague-Dawley; Rhus; Thrombosis; Wood

The aim of this paper was to evaluate active principles for diabetic complications from Rhus verniciflua. Nine compounds were isolated via bioactivity guided fractionation and isolation and tested for their effects on recombinant human aldose reductase and advanced glycation endproducts. Butein and sulfuretin isolated from ethyl acetate fraction were found to possess strongly both forms of aldose reductase and advanced glycation endproducts inhibition. The inhibitory activity of butein against a recombinant human aldose reductase (IC(50) value: 0.5 microM) was 2.6 times more potent that of epalrestat as a positive control (IC(50) value: 1.3 microM). The inhibitory potency of sulfuretin (IC(50) value: 124.7 microM) on advanced glycation end-products was about 10 times more potent that of aminoguanidine as a positive control (IC(50) value: 1231.0 microM). These compounds all displayed antioxidative activity which was measured by Photochem apparatus. It was concluded, therefore, butein and sulfuretin have antioxidative as well as aldose reductase and advanced glycation endproducts inhibitory effects. As a result, these compounds could be proposed as a leading compound for further study as a new natural products drug that could be used for diabetic complications.

Topics: Aldehyde Reductase; Benzofurans; Chalcones; Enzyme Inhibitors; Flavonoids; Free Radical Scavengers; Glycation End Products, Advanced; Humans; Kinetics; Plant Bark; Recombinant Proteins; Rhus

Aspergillus alliaceus UI315 was examined for its potential to catalyze biotransformation reactions of chalcones that mimic plant biosynthetic processes. 3-(4' '-Hydroxyphenyl)-1-(2',4'-dihydroxyphenyl)propenone (4,2',4'-trihydroxychalcone, isoliquiritigein) (1) was efficiently transformed to two major metabolites that were isolated chromatographically and identified by spectroscopic methods as 3-(3' ',4' '-dihydroxyphenyl)-1-(2',4'-dihydroxyphenyl)propenone (butein) (7) and 2-[(3,4-dihydroxyphenyl)methylene]-6-hydroxy-3(2H)benzofuranone (7,3',4'-trihydroxyaurone, sulfuretin) (10). Inhibition experiments suggested that initial C-3 hydroxylation of 1 to 7 was catalyzed by a cytochrome P450 enzyme system. A second A. alliaceus enzyme, partially purified and identified as a catechol oxidase, catalyzed the oxidation of the catechol butein (7) likely through an ortho-quinone (8) that cyclized to the aurone product 10. This work showed that A. alliaceus UI315 contains oxidative enzyme systems capable of converting phenolic chalcones such as 1 into aurones such as 10 in a process that mimics plant biosynthetic pathways.

Topics: Aspergillus; Benzofurans; Chalcone; Chalcones; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Flavonoids; Hydroxylation; Magnetic Resonance Spectroscopy; Oxidation-Reduction