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  • articleNo Access

    Protective Effects of HV-P411 Complex Against D-Galactosamine-Induced Hepatotoxicity in Rats

    This study examined the hepatoprotective effect of the HV-P411 complex, an herbal extract mixture from the seeds of Vitis vinifera, Schisandra chinensis and Taraxacum officinale, against D-galactosamine (D-GalN)-induced hepatitis. Hepatotoxicity was induced by D-GalN (700 mg/kg, i.p.), and the HV-P411 complex was administered orally 48, 24, and 2 h before and 6 h after D-GalN injection. Increases in serum aminotransferase activity and lipid peroxidation and a decrease in hepatic glutathione content were attenuated by the HV-P411 complex 24 h after D-GalN treatment. The HV-P411 complex attenuated the increases in serum tumor necrosis factor-α, interleukin (IL)-6 level and cyclooxygenase-2 protein production and their mRNA expressions, while increases in serum IL-10 level and heme oxygenase-1 protein production and their mRNA expressions were augmented by the HV-P411 complex. The increased translocation of nuclear factor-κB and c-Jun phosphorylation were attenuated by treatment with the HV-P411 complex. Our results suggest that the HV-P411 complex prevents D-GalN-induced hepatotoxicity via antioxidative and anti-inflammatory activities.

  • articleNo Access

    AP-1-Targeted Inhibition of Macrophage Function and Lipopolysaccharide/D-Galactosamine-Induced Hepatitis by Phyllanthus acidus Methanolic Extract

    Traditionally, Phyllanthus acidus (Phyllanthaceae) has been used for the treatment of rheumatism, bronchitis, asthma, respiratory disorders, and hepatitis. Recently, we showed that a methanol extract of Phyllanthaceae (Pa-ME) has a potent anti-inflammatory activity in RAW264.7 cells and strongly ameliorates HCl/EtOH-induced gastric ulcers in mice by targeting the Src/Syk of NF-κB. In the present study, we explored the molecular mechanism of Pa-ME on the AP-1 activation pathway and evaluated its potential hepatoprotective effects. To do this, we employed lipopolysaccharide (LPS)-stimulated RAW264.7 cells and U937 cells and an LPS/D-galactosamine (D-GaIN)-induced acute hepatitis mouse model. We utilized a multitude of assays, including immunoblotting analysis, reporter gene assays, and mRNA expression analysis, to determine the effect of Pa-ME on the AP-1 pathway. Pa-ME strikingly suppressed the production of LPS-induced pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, Pa-ME also strongly inhibited activator protein-1 (AP-1) activation and mitogen-activated protein kinase (MAPK) phosphorylation in LPS-stimulated RAW264.7 macrophages cells and the U937 monocyte like human cell line. Moreover, pre-treatment with Pa-ME exhibited strong hepatoprotective and curative effects in an LPS/D-Gal-induced mouse hepatitis model as evidenced by a decrease in elevated serum AST and ALT levels and the amelioration of histological damage. Taken together, our data suggest that Pa-ME might play a crucial ethnopharmacological role as a hepatoprotective herbal remedy by suppressing MAPK signaling and the activity of the downstream transcription factor AP-1.

  • articleNo Access

    Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) Attenuates Inflammatory Symptoms of Gastritis, Hepatitis and Arthritis

    Korean Red Ginseng (KRG) is an herbal medicine prescribed worldwide that is prepared from Panax ginseng C.A. Meyer (Araliaceae). Out of ginseng’s various components, ginsenosides are regarded as the major ingredients, exhibiting anticancer and anti-inflammatory activities. Although recent studies have focused on understanding the anti-inflammatory activities of KRG, compounds that are major anti-inflammatory components, precisely how these can suppress various inflammatory processes has not been fully elucidated yet. In this study, we aimed to identify inhibitory saponins, to evaluate the in vivo efficacy of the saponins, and to understand the inhibitory mechanisms. To do this, we employed in vitro lipopolysaccharide-treated macrophages and in vivo inflammatory mouse conditions, such as collagen (type II)-induced arthritis (CIA), EtOH/HCl-induced gastritis, and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-triggered hepatitis. Molecular mechanisms were also verified by real-time PCR, immunoblotting analysis, and reporter gene assays. Out of all the ginsenosides, ginsenoside Rc (G-Rc) showed the highest inhibitory activity against the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferons (IFNs). Similarly, this compound attenuated inflammatory symptoms in CIA, EtOH/HCl-mediated gastritis, and LPS/D-galactosamine (D-GalN)-triggered hepatitis without altering toxicological parameters, and without inducing gastric irritation. These anti-inflammatory effects were accompanied by the suppression of TNF-α and IL-6 production and the induction of anti-inflammatory cytokine IL-10 in mice with CIA. G-Rc also attenuated the increased levels of luciferase activity by IRF-3 and AP-1 but not NF-κB. In support of this phenomenon, G-Rc reduced TBK1, IRF-3, and ATF2 phosphorylation in the joint and liver tissues of mice with hepatitis. Therefore, our results strongly suggest that G-Rc may be a major component of KRG with useful anti-inflammatory properties due to its suppression of IRF-3 and AP-1 pathways.

  • articleNo Access

    Hepatoprotective Effect of Wedelolactone against Concanavalin A-Induced Liver Injury in Mice

    Eclipta prostrata L. is a traditional Chinese herbal medicine that has been used in the treatment of liver diseases. However, its biological mechanisms remain elusive. The current study aimed to investigate the hepatoprotective effect of wedelolactone, a major coumarin ingredient of Eclipta prostrata L., on immune-mediated liver injury. Using the well-established animal model of Concanavalin A (ConA)-induced hepatitis (CIH), we found that pretreatment of mice with wedelolactone markedly reduced both the serum levels of transaminases and the severity of liver damage. We further investigated the mechanisms of the protective effect of wedelolactone. In mice treated with wedelolactone prior to the induction of CIH, increases of serum concentrations of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-6 were dramatically attenuated. Additionally, expressions of the interferon-inducible chemokine (C-X-C motif) ligand 10 gene CXCL10 and intercellular adhesion molecule 1 gene ICAM1 were lower in livers of the treated mice. Moreover, wedelolactone-treated CIH mice exhibited reduced leukocyte infiltration and T-cell activation in liver. Furthermore, wedelolactone suppressed the activity of nuclear factor-kappa B (NF-κB), a critical transcriptional factor of the above-mentioned inflammatory cytokines by limiting the phosphorylation of I kappa B alpha (IκBα) and p65. In conclusion, these findings demonstrate the inhibitory potential of wedelolactone in immune-mediated liver injury in vivo, and show that this protection is associated with modulation of the NF-κB signaling pathway.

  • articleNo Access

    CLINICAL DATA ANALYSIS AND MATHEMATICAL MODELING OF MIXED INFECTIONS

    Quantitative analysis data describing course of viral hepatitis show that concominal viral respiratory infection did not influence hepatitis severity and the rate of recovery after it. In the groups of hepatitis patients with different severity we also found the upper respiratory infections increasing proportional to the hepatitis severity. The rhinoviral infection initiation model in healthy and in hepatitis patients was obtained. Using this model allowed us to describe the phenomenon of upper respiratory infection incidence increasing in viral hepatitis dynamics.

  • articleNo Access

    Research News

      Implantable Contact Lens Developed.

      Study Shows GM-free Zones Unnecessary.

      Melbourne Scientists Grow Thymus Organ.

      Artificial Livers to Cure Hepatitis.

      University of Tokyo Selects Olympus SNP Typing System for Research.

      Chronic Fatigue Linked to Low Serotonin.

      Tanabe Seiyaku and GSK to Collaborate on Genome Drug Discovery.

      Anti-alcoholic Gene in Polynesians Shows Asia-pacific Ancestry.

      Tooth Minerals Replenished by Milk.

    • articleNo Access

      Industry Watch

        AustCancer Acquires Galenica Pharmaceuticals Inc.

        New Approved National New Drugs.

        Hepatitis Blockbuster?

        Antithrombotics Market in China.

        Win-win Partnership between Orchid and Par Pharma.

        Japan Tobacco Inc. Launches HIV Drug in Japan.

        Daiichi Markets Ototopical Antibiotic in Single-dispensing Container.

        IP: Eye on Singapore’s Biomedical Science Industry.

        Singapore’s Biomedical Science Industry’s 2003 Performance.

      • articleNo Access

        Industry Watch

          Aspect Medical Systems and Brain Resource Company Partners in MCI Study.

          Mesoblast and Cordis Collaborate on Adult Stem Cell Heart Trial.

          Apollo Life Sciences Begins Sale of Human Cell-Expressed Proteins Globally.

          Workhardt Introduces Hepatitis A Vaccine into Indian Market.

          Transgene Biotek Develops Oral Delivery of Insulin and Hepatitis B Vaacine.

          Japan's Bioventures Today - Peruseus Proteomics Inc.

        • articleNo Access

          BIOBOARD

            INDIA – Lack of access to technology ‘hampers detection of substandard drugs’.

            JAPAN – Daiichi Sankyo announces development of nucleic acid treatment for Duchenne muscular dystrophy utilizing proprietary technology.

            SINGAPORE – IBN creates unlimited source of human kidney cells.

            SINGAPORE – Dyesol and Singapore's NTU sign agreement.

            THE PHILIPPINES – Global biotech/GM crop plantings increase 100-fold from 1996.

            AUSTRALIA – Phosphagenics further expands pain portfolio.

            AUSTRALIA – Primary Health Care signs Australia distribution agreement for iGeneScreen™ prenatal test.

            AUSTRALIA – Folic acid in pregnancy linked with reduced autism risk.

            AUSTRALIA – Phylogica and Bio-Link collaborate to commercialize anti-inflammatory Phylomers.

            AUSTRALIA – ABRAXANE® plus gemcitabine improves survival in Phase III study of patients with advanced pancreatic cancer.

            CANADA – Verisante Technology, Inc. announces first sales of aura, a revolutionary medical device for the detection of skin cancer.

            EUROPE – Project eyes robust medical technology for poor countries.

            UNITED KINGDOM – Asthma sufferers have more lung fungi.

            UNITED KINGDOM – Pioneering drug discovery gets major funding to move to next stage.

            UNITED STATES – Gilead's sofosbuvir for hepatitis C meets primary endpoint in fourth pivotal Phase III study.

            UNITED STATES – Eleven Biotherapeutics publishes data on EBI-005, a novel IL-1 inhibitor protein for topical treatment of dry eye disease.

            UNITED STATES – Phase I/II trial of ADXS-HPV in anal cancer conducted by Brown University Oncology Group.

            UNITED STATES – Scopolamine: An old drug with new psychiatric applications.

            UNITED STATES – New bioengineered ears look and act like the real thing.

            UNITED STATES – To trap a rainbow, slow down light.

            UNITED STATES – AB SCIEX responds to milk contamination concerns with new method to detect dicyandiamide.

          • articleNo Access

            BIOBOARD

              AUSTRALIA – Potential of Anisina to become major new chemotherapy.

              AUSTRALIA – Phylogica peptide fusion kills aggressive breast cancer cells.

              INDIA – South Asia running out of groundwater.

              JAPAN – Fruit fly studies shed light on adaptability.

              KOREA – Hanmi Pharm begins phase 2 clinical trials on new long-acting human growth hormone drug.

              MALAYSIA – Researchers discover breakthrough treatment for depression.

              MALAYSIA – New diagnosis tool pushed to cope with diabetes in Asia.

              SINGAPORE – Scientists discover gene that allows a peek into the future on eye disease.

              SINGAPORE – Babies from moms with hepatitis have better immune systems.

              THE PHILIPPINES – Debate persists on pneumonia vaccine in the Philippines.

              VIETNAM – Second hookworm genome hoped to lead to vaccines.

              AFRICA – Shop-based malaria kit boosts testing for disease.

              BRAZIL – Prospective Chagas vaccine proves effective in trials.

              EUROPE – Vaccine against placental malaria to start human tests in Germany and Benin.

              SRI LANKA – Sri Lankan farmers told to adapt to changing climate.

              UNITED STATES – Genetic markers play a role in who benefits from aspirin, NSAIDs to lower colon cancer risk.

              UNITED STATES – Potential Ebola treatment mechanism discovered.

              UNITED STATES – Researchers develop new potential drug for rare leukemia.

              UNITED STATES – Researchers find new link between neurodegenerative diseases and abnormal immune responses.

            • articleNo Access

              EMPIRICAL DATA AND MATHEMATICAL STRUCTURES IN THE EPIDEMIC MODELING OF PARENTERAL HEPATITIS IN ITALY

              Viral liver infections with parenteral transmission in Western countries are mostly caused by hepatitis B and hepatitis C viruses (HBV and HCV). This paper presents a mathematical model that describes the history of the spread of HBV and HCV infections in the general population in Italy. The analysis of the model and the results also provide some new insight into the mechanisms of the epidemics. The model structure is based on an underlying analysis of the various effects of the infection progression in the host, in order to incorporate into its parameters most of the information available from the literature. Moreover, incidence and prevalence curves of both HBV and HCV infections and of HBV/HCV co-infections are generated and qualitative aspects of the epidemic, such as possible endemic steady states and the basic reproduction number, are also analyzed.

            • chapterNo Access

              METALLOTHIONEINS AND LIVER DISEASES

              Metallothioneins (MTs) are cysteine-rich proteins capable of scavenging free radicals and sequestering metal ions. In the liver, these proteins are involved in copper and zinc metabolism, in the chelation of heavy metals, and in protection against oxidative damage. Because of their properties, MTs are involved in many liver diseases, which can be sorted into the following:

              1. Metal storage liver diseases. Zinc, which is an important anticopper agent for Wilson's disease, acts by increasing the concentration of MTs in the enterocytes, thereby reducing metal absorption. Copper also accumulates in the liver in cholestatic diseases, in which MTs are reportedly overexpressed and induced by ursodeoxycholic acid (UDCA), the main drug used to treat cholestasis. The role of MTs in hemochromatosis, an iron-accumulating disease, has yet to be established; but in animal models, it has been suggested that zinc, by increasing MT concentration, could exert a beneficial effect.

              2. Toxic liver diseases. By sequestering metal ions and scavenging free radicals, MTs protect against damage caused by exogenous toxic substances, such as cadmium and arsenic, and by the toxic effects on hepatocytes of ethanol and at in alcoholic and nonalcoholic liver diseases.

              3. Chronic viral hepatitis. By lowering the inflammatory injury, MTs have a protective action against chronic liver damage; a relationship has also been described between MTs and the severity of liver disease and the response to therapy.

              4. Hepatocellular carcinoma. MTs are downexpressed and inversely correlated with tumor stage; an inverse correlation has also been reported between MT concentrations and response to platinum chemotherapy.

              Given the ability of zinc to strongly induce MT synthesis, zinc supplementation could be useful not only in Wilson's disease, but also in other liver diseases in which MTs exert a protective effect.

            • chapterNo Access

              Reduction of post-transfusion hepatitis by exclusion of Australia antigen from donor blood in an urban public hospital

              Post-transfusion hepatitis occurred in ten of 56 (17.9 per cent) patients in 1963-1964, and in 14 of 78 (17.9 per cent) patients in 1968-1969 at Philadelphia General Hospital (PGH). Since November 1969 all donor blood has been tested for Australia antigen (Au) by immunodiffusion and later by counterelectrophoresis, and no positive units have been transfused. All patients were screened by stringent criteria to exclude any pre-existing liver disease and had repeated follow-up examinations after transfusion, including clinical examination, as well as serial serum glutamic pyruvic transaminase (SGPT) and Au determinations. Among 204 patients receiving Au-negative donor blood who could be followed adequately for six months, 12 (5.9 per cent) hepatitis patients (four icteric) were detected. These results indicate a two thirds reduction from the 18 per cent incidence in post-transfusion hepatitis at PGH found on two previous studies. Au testing to exclude positive donors and administering only Au-negative blood, and the changes in composition of the donor population which resulted, were effective in reducing the incidence of post-transfusion hepatitis.