Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-9) on interleukin-12 production in patients with HCV-positive liver cirrhosis.
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Interleukin-12 (IL-12) is an important cytokine for maintenance of normal systemic defense and bioregulation. The Japanese herbal medicine Sho-saiko-to (TJ-9) has been administered to 1.5 million Japanese patients with chronic liver diseases. TJ-9 is known to significantly suppress cancer development in the liver and has macrobiotic effects. In the present study, we examined the in vitro production of IL-12 by circulating mononuclear cells from liver cirrhosis patients and the effects of TJ-9 on IL-12 production. The monocyte/macrophage fraction and the lymphocyte fraction of peripheral blood were obtained from 11 HCV-positive liver cirrhosis patients and 12 healthy subjects. Interleukin-12 levels in the supernatants were measured using ELISA kits. The levels of IL-12 produced by the patients' fractions were significantly lower than those produced by healthy subjects (p < 0.01, p < 0.05). However, when TJ-9 was added to the cultures, the IL-12 production levels in both cell fractions increased approximately three fold, and the levels from the monocyte/macrophage fraction were almost the same as those from healthy subjects. This effect of TJ-9 was attributable to two of its seven herb components, that is, scutellaria root and glycyrrhiza root. One possible mechanism for the macrobiotic effects of TJ-9 on liver cirrhosis patients may be the improvement in IL-12 production. (+info)
Inhibitory effects of combined administration of antibiotics and anti-inflammatory drugs on lung tumor development initiated by N-nitrosobis(2-hydroxypropyl)amine in rats.
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The effects of antibiotics and anti-inflammatory drugs on the promotion stage of lung carcinogenesis initiated with N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats were investigated in two experiments with a similar protocol. In experiment 1, rats received tap water containing 2000 p.p.m. BHP for 12 weeks followed by basal diet or basal diet containing 0.02% erythromycin (EM), 0. 04% ampicillin (ABPC), 1.5% sho-saiko-to, 0.02% EM plus 1.5% sho-saiko-to or 0.04% ABPC plus 1.5% sho-saiko-to for 8 weeks after BHP administration. The development of adenocarcinomas (AC), squamous cell carcinomas (SqC) and adenosquamous carcinomas (ASqC) was completely inhibited in rats given ABPC plus sho-saiko-to and the numbers of lung lesions including alveolar hyperplasias, adenomas and carcinomas were decreased in rats given EM plus sho-saiko-to or ABPC plus sho-saiko-to. Neutrophil and macrophage infiltration into alveolar spaces of the lung were also markedly suppressed. In experiment 2, rats received BHP in the same manner as in experiment 1 and basal diet or basal diet containing 0.04% ABPC, 0.006% piroxicam, 0.04% ABPC plus 0.006% piroxicam and 0.04% ABPC plus 0.75% ougon for 8 weeks. The incidence and number of carcinomas, including ACs, SqCs and ASqCs were decreased in rats given ABPC plus piroxicam or ABPC plus ougon. Bacteria, mainly Escherichia coli, were detected in broncho-alveolar lavage of rats receiving BHP. The results suggest that chronic inflammation might be involved in the progression of lung carcinogenesis by BHP in rats and its suppression may therefore be useful as a chemopreventive strategy in lung cancer clinics. (+info)
Antibacterial activities of cryptotanshinone and dihydrotanshinone I from a medicinal herb, Salvia miltiorrhiza Bunge.
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Cryptotanshinone and dihydrotanshinone I, constituents of a medicinal plant, Salvia miltiorrhiza Bunge, had antibacterial activity against a broad range of Gram positive bacteria. These compounds generated superoxide radicals in Bacillus subtilis lysates. A recombination-deficient mutant strain of B. subtilis was 2- to 8-fold more sensitive than a wild strain, and this hypersensitivity was reduced in the presence of dithiothreitol as an antioxidant. DNA, RNA, and protein syntheses in B. subtilis were non-selectively inhibited by these compounds. These results suggest that superoxide radicals are important in the antibacterial actions of the agents. (+info)
Antagonistic effects of Ginkgo biloba extract on adhesion of monocytes and neutrophils to cultured cerebral microvascular endothelial cells.
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AIM: To study the action of Ginkgo biloba extract (GbE) on tumor necrosis factor (TNF-alpha)-induced adhesion of monocytes (Mon) and neutrophils (Neu) to cultured cerebral microvascular endothelial cells. METHODS: TNF-alpha-induced endothelial adhesivity toward Mon and Neu was studied using bovine cerebral microvascular endothelial cells (BCMEC) in vitro. The number of Mon and Neu adhering to the BCMEC monolayers was determined by flow cytometry. RESULTS: Pretreatment of BCMEC with TNF-alpha increased Mon and Neu adhesion to BCMEC from 12.5% +/- 0.2% to 31.3% +/- 0.5% and from 13.8% +/- 0.4% to 32.1% +/- 0.5%, respectively. GbE (1-100 mg.L-1) inhibited the effect of TNF-alpha in a concentration-dependent manner. E-selectin mAb (1 mg.L-1) blocked Mon and Neu adhesion to BCMEC induced by TNF-alpha. CONCLUSION: The inhibition of GbE on Mon and Neu adhesion to BCMEC was mediated through the suppression of E-selection expression. (+info)
Protective effects of Ginkgo biloba extract on cultured rat cardiomyocytes damaged by H2O2.
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AIM: To investigate the influence of Ginkgo biloba extract (GbE) on cardiomyocytes damaged by H2O2. METHODS: Cultured rat cardiomyocytes were divided into 3 groups randomly: control group; H2O2 (2.5 mmol.L-1) group; H2O2 2.5 mmol.L-1 + GbE 150 mg.L-1 group. The cardiomyocytes were cultured in MEM (Eagle's) at 37 degrees C in the presence of 5% CO2 for 4 h. Lactate dehydrogenase (LDH) was assayed by colorimetric method. Lipid peroxidation was determined by measuring thiobarbituric acid-reactive substances. Ultrastructure was viewed under transmission electron microscope. RESULTS: Compared with the control group, LDH leakage and malondialdehyde (MDA) content increased in H2O2 group, LDH increased from (2166 +/- 247) U.L-1 to (5180 +/- 648) U.L-1, MDA increased from (3.5 +/- 0.2) nmol/10(6) cells to (7.2 +/- 0.4) nmol/10(6) cells (P < 0.01). The ultrastructure was damaged seriously. GbE inhibited the increase of LDH leakage and MDA content induced by H2O2. In this group, LDH decreased from (5180 +/- 648) U.L-1 to (3496 +/- 386) U.L-1, MDA decreased from (7.2 +/- 0.4) nmol/10(6) cells to (4.8 +/- 0.9) nmol/10(6) cells (P < 0.01). Ultrastructure of cells was also protected by GbE. CONCLUSION: GbE protected the cardiomyocyte against H2O2 injury, the protective action was attributed to its antiperoxidative effect. (+info)
Effects of antitumor compounds isolated from Pteris semipinnata L on DNA topoisomerases and cell cycle of HL-60 cells.
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AIM: To study the effect of the antitumor compounds 5F, 6F, and A from Pteris semipinnata L on the activities of DNA topoisomerases and cell cycle of HL-60 cells, and the synergism of compound 6F in combination with genistein in vitro. METHODS: DNA topoisomerases were isolated from HL-60 cell lines, and supercoiled pBR322 DNA was used as substrate to determine the activities of DNA topoisomerase I and II. Cell cycle was analyzed by flow cytometry (FCM). Cytotoxicity assay was tested by MTT method. RESULTS: Compounds 5F, 6F, and A inhibited the activities of DNA topoisomerase I and II. After exposure of the cells to compound 6F, an increase in cells in the S and G2/M phases and a decrease in cells in the G0/G1 phase of the cell cycle were observed. At low concentrations (57.8 and 115.6 nmol.L-1), compound 6F enhanced the cytotoxicity against HL-60 cell line in combination with genistein, q values were > 1.15. The enhancement times of 57.8 and 115.6 nmol.L-1 of 6F by genistein were 2.60 and 4.65, respectively. CONCLUSION: Compounds 5F, 6F, and A inhibited the activities of DNA topoisomerases of HL-60 cells. Compound 6F increased the number of cells in S and G2/M phases, decreased the population of G0/G1 phase cells, and enhanced the cytotoxicity of genistein, which had synergism with 6F in antitumor action. (+info)
Hematotoxicity of the chinese herbal medicine Tripterygium wilfordii hook f in CD34-positive human bone marrow cells.
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T2, a chloroform/methanol extract of the herb Tripterygium wilfordii Hook f, has been used in China for the treatment of autoimmune and inflammatory diseases for many years. Recent experimental evidence has confirmed that T2 has potent anti-inflammatory and immunosuppressive activity, and a United States Food and Drug Administration-approved clinical trial is currently exploring the efficacy of T2 in the treatment of rheumatoid arthritis. Despite the potential therapeutic benefits of T2, there is ample documentation that T2 is toxic, targeting, among other things, the hematopoietic system, and its use has resulted in cases of leukopenia, thrombocytopenia, and aplastic anemia. This investigation was undertaken to characterize the in vitro effects of T2 on primary human CD34-positive (CD34+) bone marrow cells. Our results demonstrate that T2 has a potent inhibitory effect on the clonogenic response of human bone marrow cells to exogenously added hematopoietic growth factors. The inhibition of colony formation by T2 is not the result of direct cytotoxicity or increased apoptosis and indicates a functional suppression of hematopoiesis. Additional experiments demonstrate that T2 also alters transcriptional regulation in bone marrow cells by inhibiting nuclear factor-kappaB. This transcription factor is found in CD34+ bone marrow cells and has been recently shown to be a requirement for colony formation. These results demonstrate that therapeutic concentrations of T2 exert a significant hematotoxic effect by inhibiting growth factor response in CD34+ bone marrow cells and suggest that inhibition of nuclear factor-kappaB may play a role in the blood dyscrasias encountered with the use of this drug. (+info)
Effects of the Chinese medicine, TSJN on insulin resistance and hypertension in fructose-fed rats.
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The aim of this study was to determine the effect of Tang-Shen-Jiao-Nang (TSJN), a Chinese medicine used to treat diabetes mellitus, on insulin resistance and hypertension in fructose-fed rats (FFR). Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or a fructose-rich chow (FFR) for 6 wk. For the last 2 or 4 wk of a 6-wk period of either diet, the rats were treated by gavage with gum arabic solution as a vehicle (control or FFR) or TSJN (800 mg/kg/d; FFR+TS), and then we performed the euglycemic hyperinsulinemic glucose clamp technique to estimate insulin sensitivity. Systolic blood pressure was measured weekly for 6 wk. At the end of the glucose clamp, the soleus muscle was dissected out for determination of muscle fiber composition by ATPase methods. Systolic blood pressure was elevated at 2 wk after the start of the fructose-rich chow feeding and persisted thereafter throughout the study. Systolic blood pressure during the glucose clamp in the FFR group was significantly higher than that in the control group. Although there was no effect on systolic blood pressure in rats treated with TSJN for the last 2 wk of their 6-wk diet, those treated with TSJN for the last 4 wk of their 6-wk diet had lower systolic blood pressure than did the rats in the FFR group. The average rate of glucose infusion during the glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR than in the controls (10.9 +/- 0.6 and 15.4 +/- 0.4, mg/kg/min, for FFR and controls, respectively; p< 0.01). Treatment with TSJN for 2 wk significantly improved the M value compared to that of the control level (15.1 +/- 0.5 mg/kg/min). The composite ratio of type I fibers in the soleus muscle was significantly decreased in the FFR compared to controls (75.0 +/- 1.7 and 81.7 +/- 1.5%, for FFR and controls, respectively; p< 0.01), and treatment with TSJN for 2 wk led to a recovery composite ratio of type I fiber to the same level as that of the control group (78.7 +/- 1.7% in FFR + TS). The M value was significantly correlated with the compositions of type I and type II fibers (for type I fibers, r= 0.45, p < 0.01, for type II fibers, r= -0.44, p< 0.05). These results suggest that the Chinese medicine TSJN may improve insulin resistance, lower the systolic blood pressure, and modulate muscle fiber composition in hypertensive and insulin-resistant fructose-fed rats. (+info)