General pharmacological properties of Sho-seiryu-to (TJ-19) extracts.

The general pharmacological properties of TJ-19 extracts were orally investigated in various experimental animals. TJ-19 extracts showed no effect on general behavior and on central nervous system such as spontaneous locomotor activity, proconvulsant and anti-convulsant responses, analgesic activity, body temperature and hexobarbital sleeping time at all doses of 0.5, 1 and 2 g/kg in mice. Further, TJ-19 extracts showed no effect on contractile responses of isolated guinea pig ileum induced by acetylcholine, histamine and BaCl2 at concentrations of 10(-6), 10(-5), and 10(-4) g/ml. TJ-19 extracts, however, increased the respiratory rate, heart rate, blood pressure, systolic pressure, diastolic pressure, and decreased the blood flow in dogs at all doses of 0.5, 1 and 2 g/kg via duodenal administration. Further, TJ-19 extracts decreased the interval of PR and QT of EKG parameters in dogs at doses of 1 and 2 g/kg. TJ-19 extracts increased the intestinal transport of charcoal meal in rats at doses of 1 and 2 g/kg. TJ-19 increased the urinary Na+ excretion at all doses of 0.5, 1, and 2 g/kg, and increased the urinary K+ and Cl- excretion at 1 and 2 g/kg, although it showed no effect on urine volume output in rats. These data suggest that TJ-19 stimulates the sympathetic nervous system function at a pharmacological dose of under 0.5 g/kg, and has possibility to increase the intestinal peristalsis and urinary electrolyte excretion at higher doses.

The structure of physalin T from Physalis alkekengi var. franchetti.

A new steroidal constituent named physalin T (3) was isolated from the aqueous extract of Physalis alkekengi var. francheti. Based on 1H and 13C NMR spectral studies the structure was assigned as 2,3-dihydrophysalin D, i.e., 5alpha,6beta-dihydroxy-2,3,5,6-tetrahydrophysalin B, which is the first example of a natural physalin possessing a saturated ring A moiety. The structure was confirmed by the chemical transformation from the known physalin D (2) to physalin T.

Relationship between the antidiarrhoeal effects of Hange-Shashin-To and its active components.

This study was designed to examine the relationship between the antidiarrhoeal effects of Hange-Shashin-To (TJ-14) and its active components. Oral treatment with TJ-14 at 1000 mg/kg significantly inhibited castor oil-induced diarrhoea. Both the 50% methanol eluate fraction (fraction III) and the methanol eluate fraction (fraction IV) showed antidiarrhoeal effects at oral doses of 68 mg/kg and 63 mg/kg, respectively, corresponding to 1000 mg/kg of TJ-14. TJ-14 (1000 mg/kg, p.o.) showed a significant increase in blood corticosterone levels. Increased blood corticosterone was noted after the oral administration of 63 mg/kg of fraction IV. The inhibitory activity of TJ-14 on cyclooxygenase-2 (COX-2) was also observed in fractions III and IV. The main component of fraction III was Scutellariae Radix-derived baicalin. Fraction IV contained Glycyrrhizae Radix-derived glycyrrhizin and isoliquiritin, Coptidis Rhizoma-derived berberine, coptisine and palmitine. Ginseng Radix-derived saponins were also present in fraction IV. These compounds inhibited castor-oil induced diarrhoea at oral doses of 10 or 30 mg/kg. Thus, the present results indicate that Scutellariae Radix, Glycyrrhizae Radix, Ginseng radix and Coptidis Rhizoma-derived components are involved in the antidiarrhoeal action of TJ-14.

Quantitative analysis of aristolochic acids, toxic compounds, contained in some medicinal plants.

The amounts of aristolochic acid I and II in four groups of medicinal plants from the Aristolochiaceae and some related plants were determined by high-pressure liquid chromatography, for Aristolochia was reported to produce interstitial nephritis caused by aristolochic acids during chronic use for the treatment of rheumatism, diuretic and analgesic. They were detected in all the plants that originated from the genus Aristolochia (Aristolochiaceae) and in some of the plants from the genus Asarum (Aristolochiaceae). The present results suggest that these medicinal plants should be prohibited to use for remedy due to the harmful effects attributed to aristolochic acids.

[Sairei-to inhibits the production of endothelin-1 by nephritic glomeruli(2): alisols, possible candidates as active compounds].

We have previously reported that Sairei-to (TJ-114), a Japanese herbal medicine, prevented the production of endothelin-1 in anti-GBM nephritic rats, and that Alismatis Rhizoma (Takusha in Japanese), one of the twelve herbs composing TJ-114, might be responsible for the action. In order to further clarify the antinephritic components of TJ-114, we investigated the effects of Takusha extracts on various parameters, including endothelin-1 production of glomeruli in vitro and in vivo using anti-GBM nephritic rats. MeOH-100% MeOH and MeOH-50% MeOH fractions (31.3 microgram/ml or higher) strongly inhibited an increase in endothelin-1 concentration in culture medium when they were added to a culture of glomerular cells derived from nephritic rats. In addition, oral administration of the MeOH-100% MeOH fraction (30 mg/kg) ameliorated the proteinuria, increase in systolic blood pressure and changes in histopathological parameters in nephritic rats. Oral administration of the MeOH-100% MeOH fraction inhibited increase in endothelin-1 expression in the glomeruli of nephritic rats and in endothelin-1 production by a culture of glomerular cells derived from the nephritic rats. Alisols A and B, the main constituents of the MeOH-100% MeOH fraction, inhibited in vitro endothelin-1 production by glomerular cells derived from the nephritic rats. Oral administration of alisol B (30 mg/kg) prevented the endothelin-1 expression by glomeruli and the increase in endothelin-1 production by cultured nephritic glomerular cells. Oral administration of alisol B also ameliorated the proteinuria, the increase in systolic blood pressure and the changes in histopathological parameters in the nephritic rats. These results indicate that the antinephritic action of TJ-114, resulting from the inhibition of endothelin-1 production, may be attributed to the alisols in Takusha.

Inhibitory effects of Dai-saiko-to (Da-Chai-Hu-Tang) on the progression of atherosclerotic lesions in Kurosawa and Kusanagi-hypercholesterolemic rabbits.

The inhibitory effects of the traditional herbal medicine Dai-saiko-to (Da-Chai-Hu-Tang) on the progression of the atherosclerotic lesions were studied using the spontaneous familial hypercholesterolemia (FH) model, Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Changes in blood chemistry, pathology and low-density lipoprotein (LDL) oxidation were measured in a control group and a Dai-saiko-to-treated group. In the control group, the area of atheromatous plaques of the aorta progressed between week 12 (29.1%) and 26 (51.5%). This progression of atherosclerotic lesions did not happen in the Dai-saiko-to-treated group between week 12 (26%) and 26 (27.4%). Antioxidative effects on LDL were seen in the Dai-saiko-to-treated group in weeks 16 and 18. Dai-saiko-to did not improve the hypercholesterolemia in the KHC rabbits. These results suggest that Dai-saiko-to has inhibitory effects on the development of atheromatous plaque formation in spontaneous FH model rabbits. It is possible that the antioxidative effects of Dai-saiko-to on LDL led to the beneficial effects observed in this study.