wogonoside and 5-7-dihydroxy-6-methoxy-2-phenylchromen-4-one

Scutellariae Radix (SR) and its bioactive flavones elicit a variety of effects in the brain. However, the brain uptake of individual SR flavones and its relationship to the elicited effects after SR administration remain unknown. Moreover, previous studies seldom measured pharmacokinetic and pharmacodynamic outcomes simultaneously. In the current study, the brain uptake of six major SR flavones and the anxiolytic behavior following oral administration of a SR extract at two clinically relevant doses (600 and 1200 mg/kg twice daily) were simultaneously investigated in mice (n = 18 per group). Brain and plasma concentrations of the flavones were measured by LC-MS/MS, while the anxiolytic effect was evaluated using the elevated plus maze. To further investigate the mechanism behind the differential brain uptake of the six SR flavones, these flavones were separately administered to mice at an equivalent molar oral dose (n = 6). The brain tissue bindings of the SR flavones were also measured with the in vitro brain slice method. Our results indicated that all six SR flavones including three aglycons (baicalein, wogonin, and oroxylin A) and three glucuronides (baicalin, wogonoside, and oroxyloside) could pass through the blood-brain barrier, with brain concentrations ranging from 7.9 to 224.0 pmol/g. It provided novel evidence that oroxylin A had the highest brain uptake among the six SR flavones regardless of its limited content in SR extract, in which 3.6-3.9% of the administered oroxylin A dose was present in the brain 6 h postdosing and with a brain-to-plasma ratio of 0.42-0.46. Although SR extract contains flavones that are positive modulators of the benzodiazepine binding site of GABA

Topics: Animals; Anti-Anxiety Agents; Brain; Flavanones; Flavones; Flavonoids; Glucosides; Male; Maze Learning; Mice; Mice, Inbred ICR; Scutellaria baicalensis; Tandem Mass Spectrometry

This study aims to identify and quantify the six major bioactive flavones of the traditional Chinese medicine Scutellariae Radix (RS), including baicalein, baicalin, wogonin, wogonoside, oroxylin A and oroxyloside in rat after oral administration of a standardized RS extract. A novel, sensitive and selective method for simultaneous determination of these six analytes in rat brain and plasma using solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC/MS/MS) was developed and fully validated. The lower limits of quantification (LLOQs) for the six RS flavones in brain tissue were 0.02nmol/g. The LLOQs in plasma were 0.005nmol/ml for B, W and OA, 0.025nmol/ml for WG and OAG, and 0.1875nmol/ml for BG. The current study provides novel evidence of the presence of all the tested RS flavones and an isoform of BG (BG', probably baicalein-6-O-glucuronide) in the rat brain after oral administration of RS extract, suggesting their ability to permeate through the blood-brain barrier. The method was also successfully applied to the pharmacokinetic study of all these analytes in plasma after oral administration of RS extract (300mg/kg) to Sprague-Dawley rats. The developed assay method provides a useful tool for both preclinical and clinical investigations on the disposition of RS flavones in brain and plasma.

Topics: Animals; Brain; Chromatography, Liquid; Flavanones; Flavones; Flavonoids; Glucosides; Glucuronides; Male; Rats; Solid Phase Extraction; Tandem Mass Spectrometry

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.

Topics: Administration, Oral; Animals; Area Under Curve; Chromatography, Liquid; Dinoprostone; Drugs, Chinese Herbal; Fever; Flavanones; Flavonoids; Glucosides; Interleukin-1beta; Mass Spectrometry; Monoterpenes; Rats; Tumor Necrosis Factor-alpha

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.

Topics: Administration, Oral; Animals; Chromatography, Liquid; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Flavanones; Flavonoids; Glucosides; Glycyrrhetinic Acid; Glycyrrhizic Acid; Male; Monoterpenes; Pentacyclic Triterpenes; Rats; Rats, Wistar; Spectrometry, Mass, Electrospray Ionization

A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of baicalin, wogonoside, baicalein, wogonin, oroxylin A and chrysin in rat plasma, using naringin as an internal standard. After acidifying with HCl, plasma samples were pretreated by liquid-liquid extraction with acetone. Chromatographic separation was accomplished on a Hypersil Gold-C(18) analytical column (2.1×150 mm, 5 μm) utilizing a gradient elution profile and a mobile phase consisting of (A) 0.1% formic acid in water and (B) acetonitrile. Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. All analytes showed good linearity over the investigated concentration range (r>0.9900). The lower limit of quantification was 0.5 ng/ml for baicalin, wogonoside, wogonin and oroxylin A, and 1.0 ng/ml for baicalein and chrysin. Intra-day and inter-day precisions (RSD%) were less than 15% and accuracy (RE%) ranged from -6.7% to 5.8%. The validated method was successfully applied to investigate the pharmacokinetics of the major flavonoids of Radix scutellariae extract after oral administration to rats.

Topics: Administration, Oral; Animals; Area Under Curve; Chromatography, Liquid; Drugs, Chinese Herbal; Flavanones; Flavonoids; Glucosides; Half-Life; Limit of Detection; Male; Metabolic Clearance Rate; Plant Extracts; Rats; Rats, Wistar; Reference Standards; Reproducibility of Results; Scutellaria baicalensis; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

To study the flavonoids of Scutellaria baicalensis and their bioactivities.. Chromatographic methods were used to separate compounds, spectral methods were used to determine the structures and bioactivities of the flavonoids were screened in several models in vitro.. Nine compounds were isolated and identified as baicalein (1), wogonin (2), oroxylin A (3), 5, 7, 2', 6'-tetrahydroxyflavone (4), viscidulin III (5), baicalin (6), wogonoside (7), oroxylin A-7-O-beta-D-glucuronide (8) and chrysin-6-C-alpha-L-arabinopyranosyl-8-C-beta-D-glucopyranoside (9).. Baicalein had good anti-bacteria activity, and some compounds showed inhibiting activity against IL-1beta converting enzyme. The 13C NMR data of compounds 9 were assigned correctly by 2D nuclear magnetic resonance (NMR).

Topics: Anti-Bacterial Agents; Caspase Inhibitors; Flavanones; Flavonoids; Glucosides; Scutellaria baicalensis