Hepatoprotective and antiviral functions of silymarin components in HCV infection.

Departments of Laboratory Medicine, University of Washington, Seattle, WA
Hepatology (Impact Factor: 11.19). 03/2013; 57(3). DOI: 10.1002/hep.26179
Source: PubMed
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    ABSTRACT: Background&AimsIntravenous silibinin (SIL) is a potent antiviral agent against hepatitis C virus (HCV) genotype-1. In this proof of concept case-study we tested: (i) whether interferon-alfa (IFN)-free treatment with SIL plus ribavirin (RBV) can achieve sustained virological response (SVR), (ii) whether SIL is safe and feasible for prolonged duration of treatment, and (iii) whether mathematical modeling of early on-treatment HCV kinetics can guide duration of therapy to achieve SVR.MethodsA 44 year-old female HCV-(genotype-1)-infected patient who developed severe psychiatric adverse events to a previous course of pegIFN+RBV, initiated combination treatment with 1200 mg/day of SIL, 1200 mg/day of RBV and 6000 u/day vitamin D. Blood samples were collected frequently till week 4, thereafter every 1 to 12 weeks until the end of therapy. The standard-biphasic-mathematical model was used to predict the duration of therapy to achieve SVR.ResultsBased on modeling the observed viral kinetics during the first 3 weeks of treatment, SVR was predicted to be achieved within 34 weeks of therapy. Provided with this information, the patient agreed to complete 34 weeks of treatment. IFN-free treatment with SIL+RBV was feasible, safe, and achieved SVR (week-33).Conclusions We report, for the first time, the use of real-time mathematical modeling of HCV kinetics to individualize duration of IFN-free therapy and to empower a patient to participate in shared decision making regarding length of treatment. SIL-based individualized therapy provides a treatment option for patients who do not respond to or cannot receive other HCV agents and should be further validated.This article is protected by copyright. All rights reserved.
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    ABSTRACT: Recent outbreaks of highly pathogenic and occasional drug-resistant influenza strains have highlighted the need to develop novel anti-influenza therapeutics. Here we report computational and experimental efforts to identify influenza neuraminidase inhibitors from among the 3000 natural compounds in the Malaysian-Plants Natural-Product (NADI) database. These 3000 compounds were first docked into the neuraminidase active site. The five plants with the largest number of top predicted ligands were selected for experimental evaluation. Twelve specific compounds isolated from these five plants were shown to inhibit neuraminidase, including two compounds with IC50 values less than 92 μM. Furthermore, four of the twelve isolated compounds had also been identified in the top 100 compounds from the virtual screen. Together, these results suggest an effective new approach for identifying bioactive plant species that will further the identification of new pharmacologically active compounds from diverse natural-product resources.
    Journal of Chemical Information and Modeling 01/2015; 55(2). DOI:10.1021/ci500405g · 4.07 Impact Factor
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    ABSTRACT: Herbal products have been used for centuries among indigenous peoples to treat symptoms and illnesses. Recently, their use in western countries has grown significantly, rivaling that of prescription medications. Currently, they are used mainly for weight loss and bodybuilding purposes, but also to improve well being and symptoms of chronic diseases. Many people believe that because they are natural, they must be effective and safe-these beliefs are erroneous. Few herbals have been studied in well-designed controlled trials of patients with liver or other diseases, despite testimony to the contrary. Moreover, current highly effective antiviral drugs makes efforts to treat hepatitis C with herbals redundant. Herbals are no safer than conventional drugs and have caused liver injury severe enough to require transplantation or cause death. Furthermore, their efficacy, safety, and claims are not assessed by regulatory agencies, and there is uncertainty about their reported and unreported contents. We review the history of commonly used herbals, as well as their purported efficacies and mechanisms, and their side effects. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Gastroenterology 12/2014; 148(3). DOI:10.1053/j.gastro.2014.12.004 · 13.93 Impact Factor