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Pharmacological and pathological studies on hepatic protective crude drugs from Taiwan (V): The effects of Bombax malabarica and Scutellaria rivularis.

Bombax malabarica DC and Scutellaria rivularis B. were extracted in boiling water and concentrated into 1g/ml solution to investigate their hepatoprotective effect. Carbon tertrachloride (CCL4) was injected into rat subcutaneously with a dose of 3.0 ml/kg to induce experimental acute hepatotoxicity in the animal. The activities of serum glumtamic-oxaloacetic transaminase (SGOT) and serum glutamicpyruvic transaminase (SGPT) were measured after 72 hours of CCL4 administration. The hepatopathological changes of the liver tissue were observed simultaneously with liver enzyme activities determination. The pharmacological effect of B. malabarica and S. rivularis of Taiwan was compared with that of the Bupleurum chinense from mainland China. B malabarica (p < 0.001), S. rivularis (p < 0.001) and B. chinense (p < 0.05) all demonstrated a significant reduction in the CCL4-induced SGOT and SGPT. Pathological studies of these three drugs extracts demonstrated a marked hepato-protective effects on CCL4-induced liver fatty degeneration and cell necrosis.

Alanine Transaminase↗

Hepatoprotective effects of Taiwan folk medicine: wedelia chinensis on three hepatotoxin-induced hepatotoxicity.

The hepatoprotective effects of a Taiwanese crude herb, Hwang-hua-mih-tsay (Wedelia chinensis (Osbeck) Merr.), were investigated. Acute hepatitis was induced by three hepatotoxins: carbon tetrachloride and acetaminophen in mice, and D(+)-galactosamine in rats. After treatment with W. chinensis (300 mg/kg, p.o.) at 2, 6 and 10 hours, a reduction in the elevation of serum glutamate oxaloacetic transaminase (SGOT) and glutamate pyruvic transaminase (SGPT) levels was observed at 24 hrs after hepatotoxins were administered. These serological observations were confirmed by histopathological examinations. A microscopic examination of the liver showed a marked improvement in groups receiving W. chinensis. In order to further confirm the hepatoprotective effect of W. chinensis, all pharmacological and histopathological effects were compared with Bupleurum chinense DC. (family Umbelliferae), a well documented antihepatotoxicity herb. It was concluded that W. chinensis has a definite hepatoprotective effect against liver injuries.

Acetaminophen↗

Hepatoprotective effects of Taiwan folk medicine: Ixeris chinensis (Thunb.) Nak. on experimental liver injuries.

The hepatoprotective effects of Ixeris chinensis (Thunb.) Nak. were studied on acute hepatitis induced in mice by a single dose of carbon tetrachloride (31.25 microliters/kg, ip) or acetaminophen (600 mg/kg, ip), and in rats by a single dose of beta-D-galactosamine (188 mg/kg, ip). Hepatoprotective activity was monitored by estimating the serum transaminases (SGOT and SGPT) levels and histopathological changes in the livers of experimental animals. The Ixeris chinensis (Thunb.) Nak. extracts significantly inhibited the acute elevation of serum transaminases. Histopathologically, the crude I. chinensis extract significantly ameliorated hepatotoxin-induced histopathological changes in the livers of experimental animals. All pharmacological and histopathological effects of Ixeris chinensis (Thunb.) Nak. were compared with Bupleurum chinense DC., which has been previously reported as a treatment herb for hepatitis.

Alanine Transaminase↗

The protective effect of Alstonia scholaris R. Br. on hepatotoxin-induced acute liver damage.

The hepatoprotective effect of Alstonia scholaris R. Br. on liver injuries induced by carbon tetrachloride (CCl4). beta-D-galactosamine, acetaminophen and ethanol were investigated by means of serum-biochemical and histopathological examinations. Post treatment of A scholaris reduced dose-dependently the elevation of serum transaminases level and histopathological changes such as cell necrosis, inflammatory cell infiltration, which were caused by the single administration of 32 microliters/kg CCl4 or 600 mg/kg acetaminophen in mice. A. scholaris significantly lowered 288 mg/kg beta-D-galactosamine induced serum transaminases elevation in the serum-biochemical analysis in rats. A tendency was also shown to inhibit cell necrosis and inflammatory cell infiltration caused by beta-D-galactosamine in histopathological examination. All serological and histopathological effects of A. scholaris were compared with those of Bupleurum chinense, which has been reported previously as a treatment criteria of hepatitis.

Acetaminophen↗

The hepatoprotective effects of Taiwan folk medicine ham-hong-chho in rats.

Bidens pilosa L. var minor (Blume) Sherff, B. pilosa L. and B. chilensis DC (compositae), commonly known as "Ham-hong-chho" in Taiwan, have been traditionally used for medicinal purposes. To clarify and compare the hepatoprotective effects of these three plants, we evaluated their potential effectiveness on CCl4- and acetaminophen-induced acute hepatic lesions in rats. The results indicated that the increase in SGOT and SGPT activities caused by CCl4 (3.0 ml/kg, s.c.) and acetaminophen administration (600 mg/kg, i.p.) could be significantly reduced by treating with the extracts of all the three kinds of "Ham-hong-chho" and the extract of B. chilensis exhibited the greatest hepatoprotective effects. These phenomena were also confirmed by histological observation. Liver damage induced by CCl4 and acetaminophen was markedly improved in the extract of B. chilensis treated groups, while groups treated with the extracts of B. pilosa var minor and B. pilosa demonstrated only moderate protective effects. The pharmacological and pathological effects of these three crude groups were compared with Bupleurum chinense, which has been reported previously as a treatment criteria in the CCl4 model, and with silymarin as a standard reference medicine in the acetaminophen model. The results suggest that B. pilosa var minor, B. pilosa and B. chilensis can protect liver injuries from various hepatotoxins and have potential as broad spectrum antihepatic agents.

Animals↗

Effects of lycopene and Sho-saiko-to on hepatocarcinogenesis in a rat model of spontaneous liver cancer.

The Long-Evans Cinnamon (LEC) rat is a well-characterized model of spontaneous hepatocarcinogenesis. It has been shown that dietary administration of lycopene or the herbal medicine Sho-saiko-to (TJ-9) has anticarcinogenic activity, although the mechanism by which these products protect against carcinogenesis is not well known. We investigated the outcome of administration of lycopene and TJ-9 on the occurrence of hepatic neoplasia in LEC rats. A diet containing 0.005% lycopene (originally the product of tomato oleoresin containing 13% lycopene) and 1% TJ-9 (crude extracts of 7 herbs: bupleurum root, pinellia tuber, scutellaria root, jujube fruit, ginseng root, glycyrrhiza root, and ginger rhizome) was administered from 6 weeks of age until the rats were sacrificed at 76 weeks of age, at which time most of the nontreated animals were known to have hepatocellular carcinoma (HCC). Development of HCC in treated groups was analyzed histologically by comparison with untreated controls. Glutathione S-transferase placental form (GST-P) was analyzed by an immunohistochemical method. Concentration of copper, iron, and zinc, which appear to play a role in hepatocarcinogenesis in LEC rats, was analyzed. The percent areas of HCC in the liver specimens of control, lycopene, and TJ-9 groups were 17.9 +/- 17.1%, 27.2 +/- 20.8%, and 27.6 +/- 18.4%, respectively. These intergroup differences were not significant. The percent area, number of areas, and mean size of area staining positively for GST-P revealed no significant differences between the groups. The number of GST-P-positive areas within the HCC lesions was greater in the TJ-9 group than in the control or lycopene group (p = 0.024 and p = 0.012, respectively). The study also demonstrated a lower concentration of iron in livers of the lycopene group than the control group (p = 0.019). There were no differences in serum alpha-fetoprotein levels or the cumulative survival rates between the groups. In conclusion, long-term administration of lycopene or TJ-9 did not reduce the risk of hepatocarcinogenesis in LEC rats.

Animals↗

The in-vivo effects of sho-saiko-to, a traditional Chinese herbal medicine, on two cytochrome P450 enzymes (1A2 and 3A) and xanthine oxidase in man.

The Chinese herbal medicine sho-saiko-to is a mixture of seven herbal components (Bupleurum root, Pinellia tuber, Scutellaria root, Jujube fruit, Ginseng root, Glycyrrhiza root and Ginger rhizome) that is widely administered to patients with chronic hepatitis in Japan. We assessed the effects of sho-saiko-to on the activity of cytochrome P450 (CYP) 1A2, CYP3A and xanthine oxidase (XO) in man. Twenty-six healthy subjects were studied to evaluate their baseline activity of CYP1A2 and XO by the respective urinary metabolic ratios of an 8-h urine sample after an oral 150-mg dose of caffeine and of CYP3A by a urinary excretion ratio of 6beta-hydroxycortisol (6beta-HC) to free cortisol (FC). Thereafter, the subjects received a twice-daily 2.5-g dose of sho-saiko-to for five days, and underwent the caffeine test on day 1 and day 5. The mean activity of CYP1A2 decreased by 16% on both day 1 and day 5 compared with the baseline (P=0.001). The mean activity of XO also significantly decreased by 25% on day 1 and 20% on day 5 (P<0.0001) compared with the baseline value. The activity of CYP3A tended to be lower on day 5 than the baseline (P=0.146). It is concluded that sho-saiko-to reduces CYP1A2 and XO activity in man.

Adult↗

Amplification and sequence of a 5s-rRNA gene spacer region from the crude drug "angelica root".

A 5S-ribosomal gene spacer region was amplified by the polymerase chain reaction using a DNA preparation from the crude drug "Angelica Root" as a template. The nucleotide sequence of the amplified product was identical to that of Angelica acutiloba, the source plant of "Angelica Root", but different from that of Bupleurum falcatum or Glehnia littoralis. The possibility of discriminating "Angelica Root" from other umbelliferous crude drugs based on a Hin dIII restriction site inside the spacer region was suggested.

Base Sequence↗

Antiproliferative constituents in Umbelliferae plants II. Screening for polyacetylenes in some Umbelliferae plants, and isolation of panaxynol and falcarindiol from the root of Heracleum moellendorffii.

Methanol extracts of 36 samples of 21 Umbelliferae plants were screened for polyacetylenic compounds using the ELISA for panaxytriol, and their antiproliferative activity was checked by MTT assay using the tumor cell lines MK-1, HeLa and B16F10. The presence of antiproliferative polyacetylenes was suggested in Angelica acutiloba (fruit), Anethum graveolens (root), Bupleurum rotundifolium (fruit), Carum carvi (fruit and root), Coriandrum sativum (fruit), Cryptotaenia japonica (leaf), Glehnia littoralis (fruit), Heracleum moellendorffii (root) and Torilis japonica (fruit). Panaxynol and falcarindiol were successfully isolated from the root of Heracleum moellendorffii as antiproliferative polyacetylenes.

Acetylene↗

Corticosterone secretion-inducing activity of saikosaponin metabolites formed in the alimentary tract.

The corticosterone secretion-inducing activities of saikosaponin a, saikosaponin c and saikosaponin d, isolated from the root of Bupleurum falcatum L., and 27 metabolites formed in the murine alimentary tract were studied in mice. Serum corticosterone was determined by high-performance liquid chromatography (HPLC). Intraperitoneal administration of saikosaponin a and its intestinal metabolite, prosaikogenin F, showed corticosterone secretion-inducing activity at a dose of 0.1 mmol/kg, and maximally increased it at a dose of 0.4 mmol/kg. On the other hand, the genuine sapogenin, saikogenin F, was inactive. Saikosaponin b1 and saikosaponin g, gastric metabolites of saikosaponin a, and their intestinal metabolites, prosaikogenin A, prosaikogenin H, saikogenin A and saikogenin H, were also inactive. Serum corticosterone was increased by the administration of saikosaponin d and its intestinal metabolite, prosaikogenin G, at a dose of 0.04 mmol/kg, and it reached the maximal level at the dose of 0.1 mmol/kg. Saikogenin G also showed a slight activity. A gastric metabolite of saikosaponin d, saikosaponin b2, and its intestinal metabolites, prosaikogenin D and saikogenin D, were inactive. In the experiments on saikosaponin c and its metabolites, saikosaponin c was inactive but its intestinal metabolites, especially prosaikogenin E-2, showed activity almost equal to that of saikosaponin a. Saikosaponin h and saikosaponin i, gastric metabolites of saikosaponin c, were also inactive, but their prosaikogenins showed slight activities. When these compounds were orally administered, their corticosterone secretion-inducing activities were similar to those obtained in the intraperitoneal experiment. These results suggest that a proper polar balance between the sugar moiety and the aglycone is important for the corticosterone secretion-inducing activity of saikosaponins and their metabolites.

Animals↗

Enhancement of the mutagenicity of Trp-P-1, Trp-P-2 and benzo[a]pyrene by bupleuri radix extract.

Boiling-water extract of Korean-Saiko (Bupleuri Radix, from South Korea, Bupleurum falcatum L.) enhanced the mutagenic activity of Trp-P-1, Trp-P-2 and benzo[a]pyrene with S9mix. The boiling-water extract was fractionated with ether and then n-BuOH. Both the ether and the n-BuOH fractions also enhanced mutagenicity of Trp-P-1, respectively. The n-BuOH fraction was separated into seven fractions by silica gel chromatography and the chloroform eluate had the strongest enhancing effect on the mutagenic activity of Trp-P-1 with S9mix. The chloroform eluate fraction was further separated into five spots by thin-layer chromatography. Two of the spots had the strongest enhancing effect on the mutagenic activity of Trp-P-1. Since saikosaponin is a well known component in Bupleuri Radix, the effects of its existence were tested and saikosaponins a and c were found. The enhancement activity of saikosaponin a was very weak. The effective components are now being studied.

Animals↗

[Effects of extract from a herbal drug, cnidium rhizome (senkyu), on contraction, heart rates and membrane potentials of isolated guinea pig atria].

Effects of extract from a herb, Cnidium rhizome (Senkyu), on isolated guinea pig atria were investigated pharmacologically and electrophysiologically. The methanol extract from Cnidium rhizome decreased the contraction and slightly increased the heart rates of the isolated atria. Extracts from five other herbs, such as Japanese anglica root (Toki), Peony root (Shakuyaku), Moutan bark (Botanpi), Glycyrrhiza (Kanzo), Bupleurum (Saiko), affected neither the contraction nor the heart rates. The methanol extract from Cnidium rhizome was fractionated with chloroform and water fractions. The chloroform fraction exerted potent negative inotropic and chronotropic effects in isolated atria. The contraction was attenuated by two major components in the chloroform fraction, ligustilide and senkyunolide, but the heart rates were scarcely affected by these components. The chloroform fraction induced changes in resting potentials and configurations of normal action potentials recorded in the isolated left atria: the resting potentials were depolarized, and the upstroke velocity of the action potentials decreased. Neither ligustilide nor senkyunolide exerted such effects. The upstroke velocity of action potentials recorded in partially depolarized atria was reduced by the chloroform fraction as well as ligustilide and senkyunolide. The mechanisms underlying the effects of the extract from Cnidium rhizome were discussed.

Animals↗

[Studies on antinephritic effects of plant components in rats (1). Effects of saikosaponins original-type anti-GBM nephritis in rats and its mechanisms].

This study was designed to clarify the anti-nephritic effects of the saikosaponins that are contained in Bupleurum falcatum L. crude saikosaponin at 1.0 mg and 5.0 mg/kg, i.p. prevented urinary protein excretion and elevation of serum cholesterol content on the 10th day after the injection of anti-GBM serum. Moreover, crude saikosaponin at 1.0 mg and 5.0 mg/kg, i.p. significantly inhibited histopathological changes such as hypercellularity and adhesion. On the other hand, saikosaponin a (5.0 mg/kg, i.p.) and d (1.0 mg and 5.0 mg/kg, i.p.) also prevented urinary protein excretion, elevation of serum cholesterol content, and histopathological changes. In the second study, to clarify the anti-nephritic mechanisms of saikosaponins on this model, we investigated the effect of saikosaponins on platelet aggregation, release of corticosterone and reactive oxygen species scavengers activity. Crude saikosaponin and saikosaponin d significantly inhibited the increase in platelet aggregation, and saikosaponin d enhanced the serum and intra-adrenal corticosterone levels. Crude saikosaponin and saikosaponin a inhibited the decrease in activity of scavengers (SOD, catalase, glutathione peroxidase). These results indicate that saikosaponins were effective on this model, and anti-nephritic mechanisms of saikosaponins were party due to anti-platelet, corticosterone releasing and enhancing action on the activity of reactive oxygen species scavengers.

Animals↗

The effects of saikosaponin-d on yeast phagocytosis and degradation in peritoneal macrophages: related increase in Fc receptor expression and altered cytoplasmic organization.

The effects of saikosaponin-d (ssd), isolated from Bupleurum radix, on phagocytic functions of mouse peritoneal macrophages were investigated in macrophage cultures after treatment in vivo. We also compared the ultrastructural appearances of macrophages from ssd-treated mice with those from control mice. The macrophages from ssd-treated mice showed a significant increase in phagocytosis, intracellular killing of yeast and acid phosphatase activity. Treatment of mice with ssd also induced the Fc receptor expression in macrophages. The macrophages from ssd-treated mice showed more intense spreading on a glass surface than those from the control mice after a 60 min-incubation. Furthermore, the macrophages from ssd-treated mice seemed to possess a well-developed Golgi apparatus and the large vacuoles. The data suggest that the functional changes in the macrophages from ssd-treated mice are brought about by a modification in the surface membrane and the intracellular distribution.

Acid Phosphatase↗

Treatment of complications due to peritoneal dialysis for chronic renal failure with traditional Chinese medicine.

In this paper, the experience in the treatment of complications due to continuous ambulatory peritoneal dialysis for chronic renal failure with traditional Chinese medicine (TCM) is reported. Modified Renshen Yangrong Tang (Ginseng Nutrition Decoction) was used for anorexia and hypoproteinemia; modified Xiangsha Liujunzi Tang (Decoction of Cyperus and Amomum with Six Noble Ingredients) for abdominal pain and distension; modified Da Chaihu Tang (Major Bupleurum Decoction) for peritonitis; modified Shenling Baizhu San (Powder of Ginseng, Poria and Atractylodes) for diarrhea due to insufficiency of the spleen with abundance of dampness; Lizhong Tang (Decoction for Regulating the Function of Middle-jiao) and modified Sishen Wan (Pills of Four Miraculous Drugs) for insufficiency of both the spleen and the kidney; Siwu Tang (Decoction of Four Ingredients) added with other drugs for cutaneous pruritus, and Guishao Sijunzi Tang (Decoction of Four Noble Drugs added with Chinese Angelica Root and white Peony Root) for renal anemia. The therapeutic principles of invigorating the liver and kidney, strengthening the bones and muscles, and promoting blood circulation to eliminate blood stasis were adopted in the treatment of renal osteopathy, and the therapeutic principles of invigorating the liver and kidney, expelling phlegm and resolving dampness, and promoting blood circulation to eliminate blood stasis in the treatment of hyperlipemia. Shen Tekang capsules (capsules for improving the renal function) was administered to patients for strengthening the viability and improving the nutrition state, and the recipe for treating renal function failure (both formulated by the authors) for improving the renal function so as to decrease the frequency and duration of dialysis.

Anorexia↗

Seasonal patterns of terpene content and emission from seven Mediterranean woody species in field conditions.

The seasonal pattern of terpene content and emission by seven Mediterranean woody species was studied under field conditions. Emission rates were normalized at 30°C and 1000 μmol·m·s PFD (photosynthetic photon flux density). Bupleurum fruticosum, Pinus halepensis, and Cistus albidus stored large amounts of terpenes (0.01-1.77% [dry matter]) with maximum values in autumn and minimum values in spring. They emitted large amounts of terpenes (2-40 μg·g DM·h), but with no clear seasonal trend except for Cistus albidus, which had maximum values in spring and minimum values in autumn. The nonstoring species Arbutus unedo, Erica arborea, Quercus coccifera and Quercus ilex also emitted large amounts of terpenes (0-40 μg·g DM·h) and also tended to present maximum emission rates in spring, although this trend was significant only for A. unedo. At the seasonal scale, emission rates did not follow changes in photosynthetic rates; instead, they mostly followed changes in temperature. From autumn to spring, the least volatile monoterpenes such as limonene were emitted at highest rates, whereas the most volatile monoterpenes such as α-pinene and β-pinene were the most emitted in summer. The monoterpene emission rates represented a greater percentage of the photosynthetic carbon fixation in summer (from 0.51% in Arbutus unedo to 5.64% in Quercus coccifera) than in the rest of the seasons. All these seasonality trends must be considered when inventorying and modeling annual emission rates in Mediterranean ecosystems.

Journal Article↗

[Studies on the medicinal plant in the "Sambutsu-cho" of Bungo Province possessed by the Kumamoto Clan (II); studies on the medicinal herbs].

In the previous report, I studied the medicinal trees contained in the Sambutsu-cho of the Kumamoto clan in Bungo Province. In this report, I studied the medicinal herbs contained in the same book. There were 259 names in the herbal part. I identified 156 species and found 103 species as the medicinal plants. The ratio of the medicinal plants was 66%. The famous medicinal plants were as follows: Atractilodes japonica, Platycodon gradiflorum, Mentha arvensis var. piperascens, Lisospermum erythrorizon, Pharbitis nil, Gentiana scabra var. buergeri, Cnidium officianal, Angelica acutiloba, Bupleurum falcatum, Pueraria lobata, Paeonia lactiflora, Paeonia suffruticosa, Achyranthes fauriei, Asarum dimidiatum, Ophiopogon japonica, Pinellia ternata and Cyperus rotundus.

Botany↗

[Uses of duck hepatitis B virus polymerase and reverse transcriptase in the evaluation of anti-hepatitis B virus drugs].

The method of DHBV replication complexes (RCs) purification was modified. In order to screen anti-HBV drugs from Chinese medicinal herbs, the inhibitory effects of the extracts of 14 Chinese recipes and herbs, 30 compounds isolated from Chinese herbs on DHBV DNA polymerase (DNAP) and reverse transcriptase (RT) have been studied. The results showed that extracts of Xiao Chai Hu Tang (small Bupleurum decoction) inhibited DHBV DNAP and RT in less extent. Of the 7 herbs, the components of Xiao Chai Hu Tang, the extracts of S. baicalensis and P. ternata potently inhibited DHBV RT, their concentration of reducing enzyme activity by 50% (IC50) was 1.25 and 1.6 mg/ml respectively. Furthermore, it has been proved that S. baicalensis inhibited DHBV DNA replication in ducklings. It also was found the extract of P. cuspidatum inhibited DHBV RT with IC50 of 1.76 mg/ml. Nine of thirty isolated compounds inhibited both DHBV DNAP and RT in less extent under high concentration, while other did not.

Animals↗