ABSTRACT
The study is aimed to establish a RP-HPLC method for determination of luteolin from the extracts of Elsholtzia blanda (EEB) in rats' biological specimen. A RP-HPLC method was established for determination of free and total luteolin in SD rats' plasma and gastrointestinal tract and total luteolin in SD rats' heart, liver, lung and kidney at 0.17, 0.5, 1, 2, 4 and 6 h after administration of EEB to 24 male SD rats (4 rats per one time spot). Luteolin glycoside was hydrolyzed to aglycone luteolin in intestinal tract, and then luteolin was absorbed. The main form of luteolin existed in gastrointestinal tract after administration of EEB is aglycone. The content of luteolin in liver and kidney were higher than that in heart and lung. The content of luteolin in kidney, heart and lung were showed max at 1 h. Its peak time was similar to that in blood. However, in liver, the drug was distributed quickly, and showed max at 0.17 h. And because of the sensitivity of the method, luteolin was not be detected in other tissues. The method is sensitive, specific, accurate, and is appropriate for determination of luteolin in vivo.
Subject(s)
Animals , Male , Rats , Administration, Oral , Drugs, Chinese Herbal , Pharmacokinetics , Intestinal Absorption , Lamiaceae , Chemistry , Liver , Metabolism , Luteolin , Blood , Metabolism , Plants, Medicinal , Chemistry , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
<p><b>OBJECTIVE</b>To observe the excretion of luteolin after oral administration of Elsholtzia blanda benth extracts in rats.</p><p><b>METHODS</b>Samples of urine, feces and bile were collected after oral administration of Elsholtzia blanda benth extracts in rate. After deconjugation with beta-glucuronidase/sulfatase, the levels of luteolin in urine, feces and bile were measured by RP-HPLC.</p><p><b>RESULT</b>The recovery rate of luteolin was 98.0 %-106.0 % and the extract recoveries were 85.0 %-108.0%. Relative standard deviation (RSD) of intra-and inter-day assay was less than 10.0 %. The total accumulative excretion was 37 % (11 % in urine, 26 % in feces and bile).</p><p><b>CONCLUSION</b>The established RP-HPLC method is sensitive, specific, accurate, and is applicable for determination of luteolin in rat urine,feces and bile.</p>
Subject(s)
Animals , Male , Rats , Administration, Oral , Bile , Chemistry , Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Metabolism , Pharmacokinetics , Feces , Chemistry , Lamiaceae , Chemistry , Luteolin , Pharmacokinetics , Urine , Plant Extracts , Rats, Sprague-DawleyABSTRACT
The paper summarizes the interactions between luteolin (glucosides) and drug-metabolizing enzyme from the literature of recent years and our research work. The metabolism of luteolin is chiefly mediated by phase II metabolic enzyme. Its glucosides are firstly hydrolyzed into aglycone in intestinal tract, and then absorbed and metabolized. Luteolin has the effect on the induction of CYP3A, and on the inhibition of CYPIA, 1B and 2E. Also, luteolin is an effective inhibitor of CYP2B6, CYP2C9 and CYP2D6. Luteolin can induce and inhibit UGTs and SULTs. It can also inhibit multi ABC transport proteins. Understanding the interactions between luteolin (glucosides) and drug-metabolizing enzyme has an important significance in guiding clinical use of the drug.
Subject(s)
Animals , Humans , ATP-Binding Cassette Transporters , Metabolism , Aryl Hydrocarbon Hydroxylases , Metabolism , Drug Interactions , Enzyme Induction , Glucuronosyltransferase , Metabolism , Luteolin , Metabolism , Microsomes, Liver , Metabolism , Sulfotransferases , MetabolismABSTRACT
An RP-HPLC method for determination of luteolin from Elsholtzia blanda Benth. extracts in rats' plasma was established and the pharmacokinetics of luteolin in rats was studied. Drug blood samples from caudal vein were gotten after oral administration of luteolin. Plasma samples were determined by RP-HPLC after being deproteinized with trichloroacetic acid and extracted with ethyl acetate. The calibration curve was linear in the range of 0.37-47.27 microg x mL(-1). The limit of quantification was 0.37 microg x mL(-1). The method recovery of luteolin was 93%-99%. The extract recovery was 75%-85%. RSDs of intra-and inter-day precisions were less than 5%. The concentration-time curve of luteolin after oral administration of Elsholtzia blanda Benth. extracts was fitted to two compartment open model. Two factors analysis of variance were adopted in the evaluation of gender and time spots for collection of blood. The result suggested that the gender-based difference in blood-drug concentrations had statistical significance. The metabolite in blood was identified as galcuronide. The method is sensitive, specific, accurate, and is appropriate for determination of luteolin in vivo.
Subject(s)
Animals , Female , Male , Rats , Administration, Oral , Area Under Curve , Chromatography, High Pressure Liquid , Methods , Lamiaceae , Chemistry , Luteolin , Blood , Pharmacokinetics , Plants, Medicinal , Chemistry , Rats, Sprague-Dawley , Sensitivity and Specificity , Sex FactorsABSTRACT
Cell lines of Bcap37 and Bcap37/MDR1 (the high P-glycoprotein (P-gp) expressing cell line) were used as model to investigate the different accumulations of (E)-2-(4-(diethylamino methyl) benzylidene)-5,6-dimethoxy-2,3-dihydroinden-one (BYZX) in the two kinds of cells. It was authenticated that whether BYZX was the substrate of P-gp. Meanwhile, the inhibitive effects of BYZX on the P-gp were investigated by determining the fluorescence intensity of rhodamine 123 in the model cells, with and without BYZX. A reversed-phase high-performance liquid chromatography (RP-HPLC) method was used to determine the accumulations of BYZX in the two cells. The results showed that the amount of BYZX accumulation in Bcap37/MDR1 cells were as many as those in Bcap37 cells (P > 0.05), and the concentrations of BYZX accumulated in the Bcap37/MDR1 cells did not increase when co-incubated with P-gp inhibitor verapamil. Furthermore, different concentrations of BYZX also had no effects on the efflux of rhodamine 123 (P > 0.05). These results indicated that there were no interactions between BYZX and P-gp. BYZX will not be pumped out of the cells, and it also not inhibited the P-gp. It was the useful advantage for its absorption.