Yoko Wakui

Balicalin, the predominant flavone glucuronide of scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form.

When baicalin was orally administered to conventional rats, it was detected in their plasma for 24 h after administration, but baicalein, the aglycone of baicalin, was not detected. However, when baicalin was given to germ‐free rats, only a small amount of baicalin was detected in their plasma within 2 h after the administration, its AUC0‐lim (the area under the concentration‐time curve from 0 to last determination time) being 12.0% of that in conventional rats. Subsequently, a considerable amount (55.1 ± 6.2%) of baicalin was recovered from the gastrointestinal tract even 4 h after administration. When baicalein was orally administered to conventional rats, however, baicalin appeared rapidly in their plasma at an AUC0‐lim value similar to that obtained after oral administration of baicalin, despite the absence of baicalein in plasma. When intestinal absorption was evaluated by the rat jejunal loop method, baicalein was absorbed readily, but only traces of baicalin were absorbed. Moreover, in conventional rats a small amount (13.4 ± 3.1%) of baicalin and an appreciable amount (21.9 ± 3.4%) of baicalein were recovered from the gastrointestinal tract even 4 h after oral administration of baicalin, but only a small amount (3.93 ± 1.43%) of baicalein was detected in the intestinal tract 1 h after administration of baicalein.

BIOAVAILABILITY STUDY OF GLYCYRRHETIC ACID AFTER ORAL ADMINISTRATION OF GLYCYRRHIZIN IN RATS; RELEVANCE TO THE INTESTINAL BACTERIAL HYDROLYSIS

To clarify the metabolic fate of glycyrrhizin when orally ingested, we investigated the bioavailability of glycyrrhetic acid, the aglycone of glycyrrhizin, after intravenous or oral administration of glycyrrhetic acid (5.7 mg kg−1, equimolar to glycyrrhizin) or glycyrrhizin (10 mg kg−1) at a therapeutic dose in rat.

Absorption and excretion of paeoniflorin in rats.

The absorption and excretion of paeoniflorin after intravenous and oral administration was studied in rats to evaluate the significance of paeoniflorin in the pharmacological action of Paeony root.

Interaction of drugs and Chinese herbs: pharmacokinetic changes of tolbutamide and diazepam caused by extract of Angelica dahurica.

The inhibitory effects of Angelica dahurica root extract on rat liver microsomal cytochrome P450 and drug‐drug interactions were studied.

Determination of baicalin and baicalein in rat plasma by high-performance liquid chromatography with electrochemical detection

A rapid and sensitive method, using electrochemical detection, has been developed for the determination of baicalin and baicalein, the flavonoid of Scutellariae radix, in rat plasma. Following separation by high-performance liquid chromatography, baicalin and baicalein were oxidized at a glassy carbon electrode to permit selective electrochemical detection. Absolute detection limits were found to be 5 ng/ml from 50 microliters of plasma for baicalin and 2 ng/ml from 100 microliters of plasma for baicalein. The resulting assays were suitable for pharmacokinetic studies of baicalin and baicalein in rats.

In‐vivo Assessment of Extrahepatic Metabolism of Paeoniflorin in Rats: Relevance to Intestinal Floral Metabolism

The extraction ratios of paeoniflorin in gut wall (EG), liver (EH) and lung (EL) were assessed by comparing AUCs after various routes of its administration to estimate the first‐pass effects and the metabolism by intestinal flora.

Determination of schizandrin in human plasma by gas chromatography-mass spectrometry

Schizandrin (SZ) is one of the lignan components from Schisandra fruits. A highly sensitive and precise method for the determination of SZ in human plasma was developed involving selected-ion monitoring with gas chromatography-mass spectrometry using a fused-silica capillary column. A 0.1-ml plasma sample was used for solid-phase extraction. A good linear relationship was obtained in the concentration range studied (2.0-500 ng/ml) and the method was sufficiently accurate and precise to support clinical pharmacokinetic studies. After oral administration of SZ at a dose of 15 mg to healthy male subjects, the average value of the maximum plasma concentration of SZ was 96.1 +/- 14.1 ng/ml. The plasma concentration of this substance could be monitored for 8 h after administration.

Simultaneous determination of byak-angelicin and oxypeucedanin hydrate in rat plasma by column-switching high-performance liquid chromatography with ultraviolet detection

A simple and sensitive column-switching HPLC method was developed for the simultaneous determination of two furocoumarin compounds, byak-angelicin and oxypeucedanin hydrate, which are the main components of hot water extract of Angelica dahurica root (AE), in rat plasma. Plasma sample was simply deproteinated with perchloric acid. After centrifugation, the supernatant was injected into a column-switching HPLC system consisting of a clean-up column (Symmetry Shield RP 8, 20x3.9 mm I.D.) and analytical column (Symmetry C18, 75x4.6 mm I.D.) which were connected with a six-port switching valve. The flow-rate of the mobile phase (acetonitrile-water, 20:80) was maintained at 1 ml/min. Detection was carried out at wavelength 260 nm with a UV detector. The column temperature was maintained at 40 degrees C. The calibration curves of byak-angelicin and oxypeucedanin hydrate were linear over the ranges 19.6 to 980 ng/ml (r2>0.997). The accuracy of these analytes was less than 4.4%. The intra- and inter-day relative standard deviations of byak-angelicin and oxypeucedanin hydrate were within 12.0% and 12.7%, respectively. The present method was applied for the analysis of plasma concentration from rats after administration of AE.

Protective effects of TJ-960 herbal mixture on hippocampal neuron damage induced by cobalt focus in the cerebral cortex of rats

In the cobalt focus experimental epilepsy model, severe hippocampal neuron damage occurs with marked EEG changes. The effects of TJ-960, a herbal medicine formulation, were studied on neuron damage in the CA1 area of rat hippocampus. Continuous oral administration of TJ-960 from one month prior to the cobalt application showed almost complete protection against hippocampal neuron damage induced by cobalt application to the cerebral cortex. TJ-960 also completely inhibited the EEG changes as well as the brain edema induced by cobalt application.

Biotransformation of the ipecac alkaloids cephaeline and emetine from ipecac syrup in rats

SummaryThe metabolism of cephaeline and emetine, which are the primary active components of ipecac syrup, were investigated in rats. Cephaeline-6′-O-glucuronide was found to be a biliary metabolite of cephaeline. Cephaeline (6′-O-demethylemetine) and 9-O-demethylemetine were observed to be enzyme-hydrolyzed biliary metabolites of emetine. Cephaeline was conjugated to glucuronide, while emetine was demethylated to cephaeline and 9-O-demethylemetine, and may be conjugated to glucuronides afterwards. Urine, feces and bile were collected from rats within 48 hours following the administration of ipecac syrup containing tritium (3H)-labeled cephaeline or emetine. Metabolites were separated and quantified by thin layer chromatography (TLC) or high-performance liquid chromatography (HPLC). Biliary and urinary excretion rates of3H-cephaeline were 57.5% and 16.5% of the dose, respectively. Cephaeline-6′-O-glucuronide was comprised 79.5% of biliary radioactivity and 84.3% of urinary radioactivity. Unchanged cephaeline was detected in 42.4% of the dose in feces. Biliary excretion rate of3H-emetine was 6.9% of the dose. Emetine, cephaeline and 9-O-demethylemetine comprised 5.8%, 43.2% and 13.6% in hydrolyzed bile, respectively. There were no emetine-derived metabolites in urine or feces. The occurrence of unchanged emetine was 6.8% and 19.7% of the dose in urine and feces, respectively.