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| Title: |
Effects on gene expression and viral load of a medicinal extract from Agaricus blazei in patients with chronic hepatitis C infection. |
| Author(s): |
Grinde B, Hetland G, Johnson E. |
| Extracts from the mushroom Agaricus blazei Murill (AbM) are used extensively as a non-prescription remedy against cancer and infections, including hepatitis. We previously demonstrated a potent immunomodulating effect of a particular preparation on monocytes in vitro, and a protective effect on bacterial infections in mice. Here we report the effect on gene expression in peripheral blood cells from four chronic hepatitis C patients, using global (29 k) oligo-based, single channel microarrays. The viral load was slightly, but not significantly, decreased after 1 week of AbM treatment. The cytokine genes most strongly induced in vitro were not induced in vivo. The more notable changes in mRNA levels were related to genes involved in the G-protein coupled receptor signalling pathway, in cell cycling, and in transcriptional regulation. The results suggest that the beta-glucans of the extract, which presumably are responsible for cytokine induction, did not readily enter the blood, while other components, such as substances proposed to have anticancer effects, were active in the blood. |
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Apoptosis induced by the Tibetan herbal remedy PADMA 28 in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2. |
| Author(s): |
Jenny M, Schwaiger W, Bernhard D, Wrulich OA, Cosaceanu D, Fuchs D, Ueberall F. |
| The Tibetan herbal remedy PADMA 28 revealed promising results to support treatment of atherosclerosis, Charot syndrome (intermittent claudication), chronic active hepatitis and infection of the respiratory tract. The remedy was confirmed to be closely linked with anti- and pro-oxidative properties in vitro. In this study, apoptogenic and survival effects of PADMA 28 were investigated in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2. PADMA 28 led to a concentration-dependent inhibition of cell proliferation accompanied by the accumulation of CEM-C7H2 cells in subG1 phase, fragmentation of poly (ADP-ribose) polymerase (PARP) and nuclear body formation. Treatment with PADMA 28 rescued to some extent cells over-expressing Bcl-2 from apoptosis. This finding suggests that the mechanism of action of PADMA 28 may be via interference with Bcl-2 triggered survival pathways. |
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Licorice compounds, glycyrrhizin and 18beta -glycyrrhetinic acid, are potent modulators of bile acid-induced cytotoxicity in rat hepatocytes. |
| Author(s): |
Gumpricht E, Dahl R, Devereaux MW, Sokol RJ. |
| The accumulation of hydrophobic bile acids results in cholestatic liver injury by increasing oxidative stress, mitochondrial dysfunction and activation of cell signaling pathways. Licorice root and its constituents have been utilized as anti-hepatotoxic agents against hepatitis C. The purpose of this study was to evaluate the potential modulation by a primary component of licorice root, glycyrrhizin (GL), and its metabolite, 18beta-glycyrrhetinic acid (GA) in a hepatocyte model of cholestatic liver injury. Preincubation of fresh rat hepatocyte suspensions with GL or GA reduced glycochenodeoxycholic acid (GCDC)-dependent reactive oxygen species (ROS) generation, with GA more potent than GL. Interestingly, GL and GA had opposing effects toward GCDC-induced cytotoxicity: GA prevented both necrosis and apoptosis, whereas GL enhanced apoptosis. GCDC promoted activation of caspase 10, caspase 3, and PARP; all were inhibited by GA, but not GL. Induction of apoptosis by GCDC was also associated with activation of JNK, which was prevented by GA. Activation of caspase 9 and dissipation of mitochondrial membrane potential were prevented by GA, but not GL. In liver mitochondrial studies, GL and GA were both potent inhibitors of the mitochondrial permeability transition, ROS generation, and cytochrome c release at submicromolar concentrations. Results from this study suggest that GL exhibits pro-apoptotic properties, whereas GA is a potent inhibitor of bile acid-induced apoptosis and necrosis in a manner consistent with its antioxidative effect. |
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Serum and liver micronutrient antioxidants and serum oxidative stress in patients with chronic hepatitis C. |
| Author(s): |
Yadav D, Hertan HI, Schweitzer P, Norkus EP, Pitchumoni CS. |
| OBJECTIVES: The exact pathogenesis of liver injury and fibrosis in chronic hepatitis C (CHC) is unclear. Free radicals play a role in CHC liver damage. Antioxidants (AO) (enzymatic and nonenzymatic) scavenge free radicals and prevent tissue injury. The aims of our study were to estimate serum levels of malondialdehyde (MDA), serum and liver levels of nonenzymatic fat-soluble AO, and to correlate the liver AO levels with the degree of inflammation and fibrosis on biopsy. METHODS: AO levels were estimated by high-pressure liquid chromatography in the pretreatment serum and liver biopsy specimen of 20 treatment-naive patients with CHC who were not on vitamin supplements. Serum levels of MDA were measured as a marker of increased oxidative stress. Twenty-two healthy individuals with no history of vitamin supplementation served as controls. AO analyzed were: retinol, alpha- and gamma-tocopherol, lutein, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene. RESULTS: Twenty CHC patients (11 men, nine women, mean age 48.5 +/- 7.9 yr) were studied. Patients and controls were comparable in age and sex. Serum MDA levels were significantly higher in CHC patients compared with controls (1.62 +/- 0.57 vs 0.23 +/- 0.15 micromol/L, p = < 0.0000). Serum levels of all AO except lutein were significantly decreased in CHC patients, and their levels were two to ten times lower than serum levels in controls. Liver levels of alpha-carotene (p = 0.0004), beta-carotene (p = 0.006), and lutein (p = 0.002) correlated with the serum levels, whereas the levels of retinol, alpha-tocopherol, lycopene, and beta-cryptoxanthin showed no correlation. Serum MDA levels were significantly higher in patients with moderate-to-severe inflammation or fibrosis compared with those with mild inflammation or fibrosis. The levels of all liver AO except alpha-carotene were significantly lower in patients with moderate-to-severe fibrosis. The severity of inflammation (portal or lobular) did not affect liver AO levels. CONCLUSIONS: Our findings suggest that increased oxidative stress is present in patients with CHC. Micronutrient AO are severely depleted in serum and liver tissue of patients with CHC, and liver levels of some AO appear to reflect serum levels. Increasing fibrosis is associated with decreased liver AO levels indicating that severe disease may be a consequence of AO depletion or decreased liver storage resulting from fibrosis. |
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Influence of Padma 28 on Patients with Chronic Active Hepatitis Type B |
| Author(s): |
Gladysz A, Juszczyk J, Brzosko WJ |
| 34 patients with chronic active hepatitis B (CAH-B) were treated with Padma 28 for 1 year. They were monitored by clinical and biochemical testing, as well as by serological, immunological and histological techniques. Among other results, 76.5% improved or normalized in biochemical parameters as well as in total T-cell count. The observations and results indicate that treatment with Padma 28 of patients with CAH-B fulfils two of the most important tasks for drug therapy of the disease, it influences the activity of genes of HBV and stops the progression of liver inflammation. |
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Padma 28 in patients with chronic hepatitis B - Clinical and immunological effects |
| Author(s): |
Brzosko WJ |
Since our first studies on the localization of the antigens (Hs Ag, Hbc Ag) of the hepatits B virus (HBV) there is now agreement that the inflammationary damage to the liver through chronically active hepatits B (CAH-B) is not the direct result of the virus but of the immune reaction of the organism against viral antigens. Thus chronic inflammatory reaction observed in the liver of patients with CAH-B means that the organism is unable to eliminate the viral infection of the hepatocytes through the immune reaction. This pathogenic viewpoint on CAH-B and other forms of chronic viral hepatitis (C,D) stimulated us to stop treating patients with immune-suppressive and anti-inflammatory medication.
After several years of attempting to treat patients with CAH-B with immuno-modulating compounds we came to the conclusion that the therapeutic use of the Padma 28 herbal remedy is the most suitable means of achieving a clinical, biochemical, immunological and histological benefit.
In the course of the past decade we have treated 126 adults and 52 children with CAH-B. Following a two-year treatment with Padma 28 (daily dose: 3 x 2 tablets) the following results were achieved: About 90% of the patients had their biochemical parameters normalized and the number of the T-lymphocyte subsets (CD3, CD4, CD8, CD4/CD8) improved. In about 15% of patients viral infection was eliminated. About 70% of patients seroconverted from Hbe-Ag positivity to anti-Hbe. In around 10% of the patients no clinical or serological improvement was observed following the treatment.
Padma 28 was well tolerated by the patients. Their appetite and general well being improved. Ultrasonographic tests of liver and spleen gave no indication of any cirrhotic lesions.
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PADMA 28 in the treatment of chronic active hepatitis |
| Author(s): |
Brzosko WJ, Gladysz A, Juszczyk J |
| In view of serious reservations as regards the effectiveness of traditional treatment of CAH by the immunosuppression method, investigations were undertaken, both clinical and experimental, with the preparation PADMA 28, a formula comprising of 20 herbs prepared according to traditional Tibetan lamaistic prescriptions. This formula was found to have an immunoregulatory action (favourable changes in the activity of T lymphocytes in various systems, stimulation of macrophage activity, increase of interferon synthesis and inhibition of blood platelet aggregation). In patients with active hepatitis treated for several months, a marked clinical and biochemical improvement as well as better immunological reactivity was obtained, and in some cases seroconversion in the e system with reduction of DNA HBV polymerase activity and decrease of HBsAg concentration occurred. In a morphological evaluation a regression of inflammatory changes in the liver was noted, with a recession of hepatocyte necrosis. |
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Significant reduction of viral activity in carriers of HBs after receiving an herbal drug with immunomodulant effect |
| Author(s): |
De Bac C, Taliani G, Furlan C, Bernaschi P |
| A drug consisting of a combination of oriental herbs, PADMA 28, has proved to have interferon-like and other favourable immunological effects. To verify its activity in improving HBV infection, 16 chronic carriers of HBs, of which 7 positive for Hbe and 9 for anti-Hbe, underwent a six months treatment with six tablets daily of PADMA 28. In these subjects and in as many untreated carriers ALT and HBs levels and routine HBV markers were followed up for 8-12 months. The quantity of HBs in serum was detected by ELISA and expressed as ng/ml. While in the control group no significant change of HBV markers were detected during the follow up, 11 out of the 16 treated patients showed a progressive decrease of HBs levels, ranging 5.000 to 50.000 ng/ml. That decrease appeared to be independent from Hbe and was the greatest in those subjects with the highest starting levels. Two Hbe-positive carriers seroconverted to anti-Hbe. After the drug was stopped, a moderate rise of HBs level was registered in 3 patients but the values never reached the starting ones. In some case there was a normalization of ALT levels. It is likely to conclude that PADMA 28 seems to be useful in reducing the activity and the infectivity of HB virus. |
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