In the present study, liquiritigenin-phospholipid complex (LPC) was developed and evaluated to increase the oral bioavailability of liquiritigenin. A single-factor test methodology was applied to optimize the formulation and process for preparing LPC. The effects of solvent, drug concentration, reaction time, temperature and drug-to-phospholipid ratio on encapsulation efficiency were investigated. LPCs were characterized by UV-visible spectroscopy, differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and powder X-ray diffractometry (PXRD). The apparent solubility and n-octanol/water partition coefficient were tested. The pharmacokinetic characteristics and bioavailability of the LPC were investigated after oral administration in rats in comparison with liquiritigenin alone. An LPC was successfully prepared. The optimum level of various parameters for liquiritigenin-phospholipid complex was obtained at the drug concentration of 8 mg·mL
Administration, Oral ; Animals ; Biological Availability ; Flavanones/pharmacokinetics* ; Phospholipids/pharmacokinetics* ; Rats ; Solvents

The study aimed to establish an UPLC-MS/MS method for the determination of baicalin in rat plasma,in order to study the effect of PEG400 on pharmacokinetics of baicalin and baicalein in normal and gut microbiotadysbiosis rats. Plasma was precipitated with ethyl acetate and determined by UPLC-MS/MS method,with genistein as an internal standard. In terms of specificity,linearity,range,accuracy,precision and stability,the method was suitable for the determination of baicalin in plasma. The gut microbiotadysbiosis rat model was induced through the oral administration with lincomycin hydrochloride(5 g·kg-1·d-1) for one week. Samples of plasma of rats were obtained at different time points,after the rats were administrated with baicalin,baicalin and PEG400. Baicalin in rats were detected by UPLC-MS/MS method,and pharmacokinetic parameters were calculated by DAS 3. 2. 2 software. The results showed that the β-glucosidase activity and the number of colonies in the feces of gut microbiotadysbiosis rats induced by lincomycin hydrochloride were significantly reduced. The Cmaxand AUC0-tof the baicalinand PEG400 group in the intestinal flora were significantly lower than those in the normal rat baicalin and PEG400 group. There was no significant difference in Cmaxand AUC0-tbetween the baicalin group and the baicalin+PEG400 group of gut microbiotadysbiosis rats. The Cmaxand AUC0-tof the normal rats baicalin group were significantly higher than those of the gut microbiotadysbiosis rats baicalin group and the baicalin + PEG400 group. There was no significant difference in Cmaxand AUC0-tbetween the normal rat baicalein and PEG400 group and the baicalein group. The Cmaxand AUC0-tof the baicalein group in the gut microbiotadysbiosis rats were lower than those in the normal baicalein group,but significantly higher than those in the baicalein and PEG400 group. PEG400 could increase the absorption of baicalin in normal rats,but is ineffective in gut microbiotadysbiosis rats,with no impact on the absorption of baicalein in rats.
Animals ; Chromatography, Liquid ; Dysbiosis ; drug therapy ; Flavanones ; pharmacokinetics ; Flavonoids ; pharmacokinetics ; Gastrointestinal Microbiome ; drug effects ; Polyethylene Glycols ; Rats ; Tandem Mass Spectrometry

OBJECTIVETo prepare the lyophilized powder of naringenin liposome and investigate its pharmacodynamics in rat models of acute lung injury (ALI).

METHODSNaringenin liposome was prepared by ethanol injection method and then its quality was evaluated. Also, the related characteristics was evaluated by adding mannitol (5%,W/V) as lyoprotectant to be freeze-dried. The rat ALI models were established by inhaling lipopolysaccharide (LPS) (5 mg/kg). Totally 48 female Sprague-Dawley rats were randomly divided into six groups:control group(A), LPS group(B), LPS+naringenin group(C), LPS+lyophilized liposome group(D), LPS+dexamethasone group(E), and LPS+blank liposome group(F), with 8 rats in each group. Lung wet/dry weight ratio was calculated, and the histopathological morphologies were observed under the light microscope.

RESULTSThe encapsulation efficiency of the prepared liposome was (82.44 ± 0.98)%, the average particle size was (133 ± 11)nm, and the Zeta potential was (-35.9 ± 5)mV. The angle of repose of lyophilized powder was 36℃ and the bulk density was 0.3 g/ml. Compared with the group A, the lung tissues from groups B to F showed different remarkable histopathological changes under a light microscope, including infiltration of inflammatory cells, capillary congestion, hemorrhage, and marked thickening of the alveolar wall,among which group B and F changed the most significant, followed by group C, whereas groups D and E were the lightest. The wet/dry weight ratios increased in groups B to F compared with group A in some degree, and the increase of the lung wet/dry weight ratio in group D and E was significantly lower than in group B(P=0.0012, P=0.0018).

CONCLUSIONThe technology of preparing naringenin liposome by ethanol injection is simple and feasible, and lyophilized powder has an obvious therapeutic effect on ALI.

Acute Lung Injury ; Animals ; Female ; Flavanones ; pharmacokinetics ; Lipopolysaccharides ; Liposomes ; Lung ; Rats ; Rats, Sprague-Dawley

The pharmacodynamic (PD) and pharmacokinetic (PK) properties of Huangqin Tang (HQT) were investigated in yeast-induced febrile rats. Blood sample and rectal temperature data of the rats were collected at different times after single oral administration of HQT at 20 g x kg(-1). The plasma concentrations of paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid were quantified by a sensitive liquid chromatography-tandem mass spectrometric (LC-MS) method. The blood concentrations of PGE2, 1L-1β and TNF-α were detected by radioimmunoassay (RIA). All pharmacokinetic parameters were processed by non-compartmental analysis using WinNonlin software. The potential relationship between the mean concentration of eight constituents and the antifebrile efficacy was investigated by calculating Pearson correlation coefficients. It was found that HQT had significant antifebrile efficacy in yeast-induced febrile rats, but had no effect to normal rats. The antifebrile effect of HQT can be attributed to the inhibition of PGE2, 1L-1β and TNF-α. The constituents (baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid) in febrile rats had delayed absorption and elimination, a longer residence time in the body, and higher C(max) and AUC than those in normal rats. Febrile condition could affect the pharmacokinetic behaviour of HQT in vivo; the flavonoids with the same backbone showed the similar fate in the body; baicalein and wogonin had a strong positive correlation (R > 0.66, P ≤ 0.02) with the antifebrile efficacy determined. Together, these constituents demonstrated different pharmacokinetic properties in the febrile body.
Administration, Oral ; Animals ; Area Under Curve ; Chromatography, Liquid ; Dinoprostone ; blood ; Drugs, Chinese Herbal ; pharmacokinetics ; Fever ; metabolism ; Flavanones ; pharmacokinetics ; Flavonoids ; pharmacokinetics ; Glucosides ; pharmacokinetics ; Interleukin-1beta ; blood ; Mass Spectrometry ; Monoterpenes ; pharmacokinetics ; Rats ; Tumor Necrosis Factor-alpha ; blood

To establish a method for the determination of astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin contained in Shaolin Xiaoyin tablets, in order to lay a foundation for designing late-stage dosage forms and clinical medication schemes. In this paper, efforts were made to establish a method for the determination of the blood concentration of the five components and study the in vivo pharmacokinetics in rats. The blood concentration was determined by HPLC. Phenomenex C18 column (4.6 mm x 250 mm, 5 microm) was adopted and eluted with methanol-acetonitrile-0.05% formic acid, the flow rate was 0.8 mL x min(-1), and the wavelength was 275 nm. The samples were processed by the solid phase extraction method. After oral administration of Shaoling Xiaoyin tablets, the rat bloods were collected at different time points to determine the blood concentrations. The experimental results showed that the baseline separation could be adopted for the five components, and astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin showed good linear relations within ranges of 2.48-248, 0.213 6-21.36, 0.531-53.1, 0.704-70.4, 0.253-25.3 mg x L(-1). All the five components could be absorbed in blood and excreted quickly. The method established in this paper is rapid and accurate, and could be used for in vivo analysis on preparations containing similar components. The main components in Shaoling Xiaoyin tablets could be absorbed and excreted quickly, and thus suitable to be made into sustained release tablets. Common preparations are required to be taken for 4-6 times a day.
Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; Cinnamates ; blood ; pharmacokinetics ; Coumarins ; administration & dosage ; blood ; pharmacokinetics ; Depsides ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; Flavanones ; administration & dosage ; blood ; pharmacokinetics ; Flavonols ; administration & dosage ; blood ; pharmacokinetics ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Male ; Monoterpenes ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

An HPLC-UV method was developed for the determination of total naringenin and total hesperetin in rat plasma after oral administration of Citrus aurantium Immaturus extracts and Zhizi Dahuang decoction. Plasma samples were pretreated with liquid-liquid extraction procedure and acid hydrolysis method was used for converting conjugated naringenin and hesperetin to their respective free forms. Plasma samples were separated on a C18 column (4.6 mm x 150 mm, 5 microm), using 0.1% phosphoric acid and methanol as mobile phase at a flow rate of 1.0 mL x min(-1) with gradient elution. DAS 2.0 software was applied to calculate the pharmacokinetic parameters while the SPSS 16.0 software was used for statistical analysis. Significant differences were observed, the C(max) AUC(0-t) of total naringenin in ZS group was 73.5% and 65.9% higher than those in ZZDHD group, respectively; the C(max), AUC(0-t) of total hesperetin in ZS group was 63.5% and 119.1% higher than those in ZZDHD group, respectively. There is a obvious decrease in C(max) and AUC(0-t) of total naringenin and total hesperetin after compatibility and their pharmacokinetic characteristics changed greatly due to the combination of other herbs. The established method was rapid, sensitive, selective and accurate, and it could be applied in the determination of total naringenin and total hesperetin in rat plasma.
Animals ; Chromatography, High Pressure Liquid ; Citrus ; chemistry ; Drug Incompatibility ; Drug Interactions ; Drugs, Chinese Herbal ; administration & dosage ; Flavanones ; administration & dosage ; pharmacokinetics ; Gardenia ; chemistry ; Hesperidin ; administration & dosage ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

The current study aims to investigate the pharmacokinetic properties of Huangqin Tang on different oral doses. An LC-MS method for simultaneous determination of flavonoids and terpenoids in rat plasma was developed and validated. Plasma samples were treated with hydrochloric acid (containing 1% ascorbic acid), precipitated with acetonitrile, separated on a Zorbax SB-C18 column, detected by single quadruple mass spectrometry with an electrospray ionization interface, and quantified using selected ion monitoring mode. All pharmacokinetic parameters were processed by non-compartmental analysis using WinNonlin software. The results of specificity, linearity, intra-day and inter-day precisions, accuracy, and stability for LC-MS assay were suitable for the quantification of paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid in rat plasma. The concentration-time profiles of baicalin, wogonoside, baicalein, wogonin, oroxylin A and glycyrrhizic acid showed double-peak phenomenon after Huangqin Tang was orally administered at 40 g x kg(-1) dose; all eight constituents in rat plasma showed good dose-exposure relationship within the dosage of 10-40 g x kg(-1); although plasma concentrations were different, the flavonoids with the same backbone showed the similar fate in the body with the corresponding dosage. In conclusion, the LC-MS assay was successfully applied for the pharmacokinetic study of multi-constituents of Huangqin Tang with different doses. Additionally, these constituents demonstrated good pharmacokinetic properties in the body.
Administration, Oral ; Animals ; Chromatography, Liquid ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Flavanones ; blood ; pharmacokinetics ; Flavonoids ; blood ; pharmacokinetics ; Glucosides ; blood ; pharmacokinetics ; Glycyrrhetinic Acid ; blood ; pharmacokinetics ; Glycyrrhizic Acid ; blood ; pharmacokinetics ; Male ; Monoterpenes ; blood ; pharmacokinetics ; Pentacyclic Triterpenes ; blood ; pharmacokinetics ; Rats ; Rats, Wistar ; Spectrometry, Mass, Electrospray Ionization

To analyse and compare the characteristics of the intestinal absorption of puerarin, baicalin, berberine and liquiritin in different combinations of Gegenqinlian decoction based on pharmacokinetic parameters, a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was applied for the quantification of four components in rat's plasma. And pharmacokinetic parameters were determined from the plasma concentration-time data with the DAS software package. The influence of different combinations on pharmacokinetics of four components was studied to analyse and compare the absorption difference of four components, together with the results of the in vitro everted gut model and the rat single pass intestinal perfusion model. The results showed that compared with other combinations, the AUC values of puerarin, baicalin and berberine were increased significantly in Gegenqinlian decoction group, while the AUC value of liquiritin was reduced. Moreover, the absorption of four components was increased significantly supported by the results from the in vitro everted gut model and the rat single pass intestinal perfusion model, which indicated that the Gegenqinlian decoction may promote the absorption of four components and accelerate the metabolism of liquiritin by the cytochrome P450.
Animals ; Area Under Curve ; Berberine ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Coptis ; chemistry ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Flavanones ; blood ; pharmacokinetics ; Flavonoids ; blood ; pharmacokinetics ; Glucosides ; blood ; pharmacokinetics ; Glycyrrhiza uralensis ; chemistry ; Intestinal Absorption ; Isoflavones ; blood ; pharmacokinetics ; Male ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Pueraria ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Scutellaria baicalensis ; chemistry ; Tandem Mass Spectrometry

The aim is to study the intestinal absorption of different combinations of active compounds out of Gegenqinlian decoction. Rat single pass intestinal perfusion model with jugular vein cannulated was used. Samples were obtained continuously from the outlet perfusate and the mesenteric vein. The levels of puerarin, daidzin, liquilitin, baicalin, wogonoside, jatrorrhizine, berberine and palmatine were determined by LC-MS/MS and their permeability coefficients were calculated. The results showed that Glycyrrhiza could promote the absorption of the active ingredients in Pueraria which is the monarch herb; meanwhile, Pueraria also played a role in promoting the absorption of liquilitin. Based on the Gegenqinlian decoction and the different combinations experiments, the results concerning the absorption of baicalin and wogonoside were as follows. For baicalin, Pueraria and Glycyrrhiza could promote its absorption and the effect of Pueraria was more obvious. For wogonoside, Pueraria could also promote its absorption, while Glycyrrhiza played a opposite role. Pueraria and Glycyrrhiza both played a part in promoting the absorption of jateorhizine, berberine and palmatine, the effective compounds in Coptis.
Animals ; Berberine ; analogs & derivatives ; metabolism ; Berberine Alkaloids ; metabolism ; Coptis ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Flavanones ; metabolism ; Flavonoids ; metabolism ; Glucosides ; metabolism ; Glycyrrhiza ; chemistry ; Intestinal Absorption ; Intestines ; metabolism ; Isoflavones ; metabolism ; Male ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Pueraria ; chemistry ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; Scutellaria baicalensis ; chemistry

The aim of this study is to investigate the rat intestinal absorption behavior of two main active components, liquiritin, glycyrrhizin and the extract of Glycyrrhiza uralensis. The rat intestinal perfusion model was employed. Concentrations of the compounds of the interest in the intestinal perfusate, bile and plasma samples were determined by HPLC and UPLC. At the same time, the intestinal enzymes incubation test and the partition coefficient determination, the absorption of liquiritin and glycyrrhizin alone and the extract were multiple analyzed. The results showed that the P(eff) (effective permeability) of liquiritin or glycyrrhizin alone or the extract was less than 0.3, which suggested their poor absorption in the intestine. The P(eff) of the two main active components or the extract was not significantly different in duodenum, jejunum, colon and ileum segment. The P(eff) of the glycyrrhizin in the extract had no significant difference in the four intestinal segments compared with the glycyrrhizin alone. The absorption of the liquiritin displayed significant difference (P < 0.05) at ileum segment compared with the liquiritin alone, while it had no markedly change in the other three segments. This phenomenon indicated that some ingredients in the extract might improve the absorption of liquiritin. Moreover, no parent compounds and their metabolites were found in the intestinal perfusate, bile and the plasma samples. The results demonstrated that the influence of the other ingredients in the extract on the two components might not increase the amount of liquiritin and glycyrrhizin in the bile and plasma within the duration of the test.
Animals ; Bile ; metabolism ; Colon ; metabolism ; Drugs, Chinese Herbal ; pharmacokinetics ; Duodenum ; metabolism ; Flavanones ; blood ; pharmacokinetics ; Glucosides ; blood ; pharmacokinetics ; Glycyrrhiza uralensis ; chemistry ; Glycyrrhizic Acid ; blood ; pharmacokinetics ; Ileum ; metabolism ; Intestinal Absorption ; Jejunum ; metabolism ; Male ; Plant Extracts ; pharmacokinetics ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley