Hepatoprotective and antiviral functions of silymarin components in HCV infection
Departments of Laboratory Medicine, University of Washington, Seattle, WAHepatology (Impact Factor: 11.06). 03/2013; 57(3). DOI: 10.1002/hep.26179
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- "Its antiviral effectiveness against Hepatitis B and especially Hepatitis C viruses is well defined. However, there are limited data about its antibacterial activity (Gordon et al. 2006; Tamayo and Diamond 2007; Wagoner et al. 2010; Polyak et al. 2013; Wei et al. 2013). "
ABSTRACT: Limited treatment options in infectious diseases caused by resistant microorganisms created the need to search new approaches. Several herbal extracts are studied for their enormous therapeutic potential. Silymarin extract, from Silybum marianum (milk thistle), is an old and a new remedy for this goal. The purpose of this study is to evaluate the antibacterial and antiadherent effects of silymarin besides biofilm viability activity on standard bacterial strains. Minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), antiadherent/antibiofilm activity, and effects on biofilm viability of silymarin were evaluated against standard bacterial strains. MIC values were observed between 60 and >241 μg/mL (0.25->1 mmol/L). Gram-positive bacteria were inhibited at concentrations between 60 and 120 μg/mL. Gram-negative bacteria were not inhibited by the silymarin concentrations included in this study. MBC values for Gram-positive bacteria were greater than 241 μg/mL. Adherence/biofilm formations were decreased to 15 μg/mL silymarin concentration when compared with silymarin-untreated group. Silymarin reduced the biofilm viabilities to 13 and 46 % at 1 and 0.5 mmol/L concentrations, respectively. We demonstrated that silymarin shows antibacterial and antiadherent/antibiofilm activity against certain standard bacterial strains which may be beneficial when used as a dietary supplement or a drug.
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- "In addition to its well-known hepatoprotective effects, a panel of other pharmacological activities of silybin, such as anti-cancer, has been recently reported (Zhou et al., 2008; Rajamanickam et al., 2010; Ravichandran et al., 2010; Ramasamy et al., 2011). Although silymarin and silybin are known to be safe and well-tolerated (Rutter et al., 2011; Marino et al., 2013; Zhu et al., 2013), hyperbilirubinemia caused by repressed UGT1A1 enzyme activity has been notified as a potential toxic effect (Flaig et al., 2007; Parveen et al., 2011; Rutter et al., 2011; Polyak et al., 2013; Sumida et al., 2013). Moreover, a critical concern about the use of silybin is the potential drug-drug interactions (DDI) because silybin is in most cases used in combination with a variety of other pharmaceutics. "
ABSTRACT: Silybin, a major pharmacologically active compound in silymarin, has been widely used in combination with other prescriptions in the clinic to treat hepatitis and a host of other diseases. Previous studies suggested that silybin is a potential inhibitor of multiple drug-metabolizing enzymes (DMEs); however, the in vitro to in vivo translation and the mechanisms involved remain established. The aim of this study was to provide a mechanistic understanding of the regulatory effects of silybin on principle DMEs. Silybin (50 or 150 mg/kg/day) was administered to mice for a consecutive 14 days. The plasma and hepatic exposure of silybin were detected; the mRNA, protein levels, and enzyme activities of principle DMEs were determined. The results demonstrated that the enzyme activities of CYP1A2, CYP2C, CYP3A11, and UGT1A1 were significantly repressed while little alteration of the mRNA and protein levels was observed. Silybin inhibits these DMEs in a mechanism-based and/or substrate-competitive manner. More importantly, silybin was found to be a weak agonist of PPARα as evidenced from the molecular docking, reporter gene assay and the targeting gene expression analysis. However, silybin could significantly compromise the activation of PPARα by fenofibrate, characterized with significantly repressed expression of PPARα targeting genes including L-FABP, ACOX1 and UGT1A6. This study suggests that silybin, despite of its low bioavailability, may inhibit enzyme activities of multiple DMEs in a mechanism-based mode, and more importantly, may confer significant drug-drug interaction with PPARα agonists via the repression of PPARα activation in a competitive mode. The American Society for Pharmacology and Experimental Therapeutics.
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- "It is moderately absorbed (23-47%) at the gastrointestinal tract. The maximum plasma concentration is achieved at 1-2h after oral dosing of milk thistle extract in human (Polyak et al., 2013). Silymarin is primarily excreted through the bile while some are cleared via the kidneys with a clearance half-life of 6-8 hours. "
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.
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