[Effect of Kampo medicines on the peripheral blood flow rate of betamethason-induced Oketsu syndrome mice by laser Doppler flow meter].

Stagnation of peripheral blood flow is the cause of various diseases. Changes in peripheral blood flow after oral administration of Kampo medicines in mice with betamethasone-induced oketsu syndrome and normal mice were examined using a laser Doppler blood flow meter. The Kampo medicines used were: Toki-shakuyaku-san; Kami-shoyo-san; Keishi-bukuryo-gan; Daio-botanpi-to; Tokaku-joki-to; Goshuyu-to; and Hange-koboku-to. In the oketsu mice, blood flow was improved by single-dose administration of Toki-shakuyaku-san, Kami-shoyo-san, Keishi-bukuryo-gan, Daio-botanpi-to, Tokaku-joki-to, and Goshuyu-to, but only Toki-shakuyaku-san increased blood flow significantly in normal mice. In addition, blood flow decreased after single-dose administration of Keishi-bukuryo-gan, Daio-botanpi-to, and Tokaku-joki-to in normal mice.

Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test.

We studied the effects of apigenin and 2,4,5-trimethoxycinnamic acid (TMCA) on the behavioral despair test (forced swimming test), and the central noradrenergic, dopaminergic and serotonergic activities in mice. Apigenin at intraperitoneal doses of 12.5 and 25 mg/kg significantly decreased the duration of immobility in the forced swimming test in mice. At 100 mg/kg, the duration of immobility was returned to the control level in the test. On the other hand, TMCA treatment (25-200 mg/kg, i.p.) failed to significantly alter the duration of immobility. Based on the behavioral data, we examined changes in the monoamine turnover in mice having been subjected to forced swimming for 40 min. The monoamine turnover was measured in seven brain regions. Forced swimming exposure induced a significant decrease in dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) in the striatum and amygdala and in 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytriptamine (5-HT) in the hypothalamus, and a significant increase in DOPAC/DA in the thalamus and hypothalamus and in 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG)/norepinephrine (NE) in the amygdala, frontal cortex, hypothalamus, and midbrain. Apigenin (25 mg/kg) treatment produced attenuation of forced swim test-induced decrease of DA turnover in the amygdala and increase of DA turnover in the hypothalamus. Furthermore, intraperitoneal administration of haloperidol (0.2 mg/kg), a dopamine D(2) antagonist, blocked the apigenin (25 mg/kg)-induced decrease in immobility in the forced swimming test. These behavioral and biochemical results indicate the antidepressant properties of apigenin, which may be mediated by the dopaminergic mechanisms in the mouse brain.

Inhibitory effects of urinary metabolites on platelet aggregation after orally administering Shimotsu-To, a traditional Chinese medicine, to rats.

Shimotsu-To, which consists of four herbal extracts, has been used clinically for improving abnormal blood coagulation, fibrinolysis, atherosclerosis and chronic inflammation in Japan and China. We have investigated the pharmacological relationship between the effects and chemical components of Shimotsu-To after oral administration to rats. The urinary constituents were separated and identified by three dimensional (3D-) HPLC equipped with a photodiode array detector as a new tool and the chemical structures were determined by spectroscopic methods to be trans-ferulic acid-3-O-sulfate (1), vanillic acid (2), m-hydroxyphenylpropionic acid (3), trans-ferulic acid (4) and cis-ferulic acid (5). Of these compounds, 2-5 strongly inhibited platelet aggregation induced by ADP and arachidonic acid. Compound 1, the sulfate conjugate of 4, did not show any inhibitory effect, which suggested that the inhibitory effect on platelet aggregation was inactivated by sulfate conjugation. These results indicated that compounds 2-5 partly contributed to the anti-Oketsu effect of Shimotsu-To through the inhibition of platelet aggregation.