The leaves of Perilla frutescens BRITTON var. acuta KUDO (Labiatae) are found in Hangekoubokuto, Saibokuto, and other traditional Chinese herbal remedies which are primarily used to treat inflammatory diseases, clinical depression, and anxiety-related disorders such as anxiety neurosis and anxiety hysteria. [1][2][3][4] One of the goals in our laboratory is to characterize the bioactive compounds of Perilla frutescens. Although many components such as essential oils, 5,6) flavones, 7-9) and phenylpropanoids 10,11) have been identified in Perilla frutescens, to our knowledge, the bioactive compounds for the traditional use of the herbal medicine are still unidentified.In most cases, traditional medicines are prepared by extraction with hot water and are orally administered so that the components present in the aqueous extract may be metabolized by gut flora before being absorbed into the body. Accordingly, to evaluate the bioactive compounds in the herbal medicines, investigation of the compounds actually absorbed into the body is necessary. In a preliminary work, we reported that apigenin and 2,4,5-trimethoxycinnamic acid (TMCA) (Fig. 1) were detected in the plasma and urine when an aqueous extract of P. frutescens was administered to humans. 12) Moreover, it has been reported that apigenin possesses a variety of pharmacological actions on the central nervous system, such as anxiolytic and sedative properties, [13][14][15] while to our knowledge, the effect of TMCA is not well characterized.The purpose of the present study was to examine the effect of treatment with apigenin and TMCA on immobility in the forced swimming test, which has been a useful experimental method for screening antidepressant activity, as a wide range of antidepressants, including tricyclics, monoamine oxidase inhibitors, atypicals, by reducing the duration of immobility. 16,17) Moreover, in addition to the behavioral change in the forced swimming test, the levels of norepinephrine (NE), dopamine (DA), 5-hydroxytriptamine (5-HT), and their metabolites in the striatum, hippocampus, amygdala, frontal cortex, thalamus, hypothalamus, and midbrain were used as parameters for evaluating antidepressant activity of apigenin and TMCA, and the effect of dopaminergic blockade on the anti-immobility action of apigenin in the forced swimming test was also investigated. MATERIALS AND METHODS AnimalsMale ddY mice (Japan SLC, Inc.) weighting 26-30 g were used for all the experimental. Animals were housed 5 per cage in a temperature (22Ϯ2°C), humidity (55Ϯ10%), and light (8:00-20:00) controlled room with free access to distilled water and commercial rodent chow (CE-2, Clea Japan Inc., Tokyo). All Experiments were carried out between 14:00 and 17:00 h and performed according to the Guide for Care and Use of Laboratory Animals at Tohoku Pharmaceutical University.Drugs Apigenin (Funakoshi Co., Ltd., Tokyo, Japan), TMCA (Tokyo Chemical Industry Co., Ltd., Tokyo, Japan), and haloperidol (Wako Pure Chemical Industries, Ltd., Tokyo, Japan) were uniformly dispersed...

As a part of our studies on the metabolism of natural compounds, gallic acid was orally administered to rats. The urinary metabolites were analyzed by high-performance liquid chromatography, and their structures were determined to be pyrogallol (M1), pyrogallol-1-O-beta-D-glucuronide (M2), 4-O-methylgallic acid-3-O-sulfate (M3), 2-O-methylpyrogallol-1-O-beta-D-glucuronide (M4), 2-O-methylpyrogallol (M5), 4-O-methylgallic acid (M6), and unchanged gallic acid on the basis of chemical and spectral data. The radical scavenging effects of gallic acid and its urinary metabolites were evaluated using 1,1-diphenyl-2-picrylhydrazyl radical.

Examination was made of the urinary and biliary excretion of the metabolites of genistein and genistein, the major components of Glycine and Sophora genus in rats. The urine of rats administered genistein orally contained eight metabolites. Three of these metabolites, genistein 4'-O-sulfate (M-1), genistein 7-O-beta-D-glucuronide (M-3), genistein 4'-O-sulfate 7-O-beta-D-glucuronide (M-6), were identified from spectroscopic and chemical data. The bile of rats administered genistein orally contained M-2, M-3 and M-6. M-6, a major biliary metabolite, was isolated and identified from spectroscopic and chemical data. The urine or bile of rats treated with genistein, the glycoside of genistein, contained M-1-M-8 or M-2, M-3, M-6 in the above metabolites. These findings suggest that genistein is absorbed as genistein after hydrolysis in the gastrointestinal tract. The total cumulative amounts of the two metabolites and genistein excreted in the urine during 48h, or of M-6 excreted in the bile during 36h following the oral administration of genistein, were approximately 5.7% or 16.0% of the doses administered, respectively. The result show that M-1, M-3 and M-6, having a free hydroxyl, glucuronide- or sulfate-conjugated hydroxyls at the C-7 or C-4' position, are excreted in the urine and bile as parts of the metabolites of genistein.

As a part of our search for the active metabolite from the bark of Magnolia officinalis (Magnoliaceae), the aqueous extract was orally administered to rats, and metabolites in the urine were analysed by a high-performance liquid chromatograph equipped with a photodiode array detector. When the extract was given to rats, five metabolites (sinapic acid-4-O-sulfate (1), sinapic acid-4-O-beta-glucuronide (2), sinapic acid (3), 3-[2',6-dihydroxy-5'-(2-propenyl)[1,1'-biphenyl]-3-yl]-(E)-2-propenoic acid (4), and an unchanged form, magnolol (5)) were detected in the urine. It was revealed that metabolites 1-3 and 4 were respectively derived from syringin and magnolol contained in the extract. In a human urine sample, metabolites 3-5 and dihydroxydihydromagnolol (6) were detected. These structures were identified by a combination of spectral methods and/or by comparison with authentic compounds obtained by synthesis. Among these free form metabolites (3-6), acute treatments with magnolol and dihydroxydihydromagnolol (50-100 mg kg(-1), i.p.) attenuated the forced swim-induced experimental depression in mice. The results indicated that magnolol and dihydroxydihydromagnolol were the antidepressant constituents of Magnolia officinalis.