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S DebRoy, N Hiraga, M Imamura, C N Hayes, S Akamatsu, L Canini, A S Perelson, R T Pohl, S Persiani, S L Uprichard, C Tateno, H Dahari, K Chayama
Legalon SIL (SIL) is a chemically hydrophilized version of silibinin, an extract of milk thistle (Silybum marianum) seeds that has exhibited hepatoprotective and antiviral effectiveness against hepatitis C virus (HCV) in patients leading to viral clearance in combination with ribavirin. To elucidate the incompletely understood mode of action of SIL against HCV, mathematical modelling of HCV kinetics and human hepatocyte gene expression studies were performed in uPA-SCID-chimeric mice with humanized livers. Chronically HCV-infected mice (n = 15) were treated for 14 days with daily intravenous SIL at 469, 265 or 61...
September 2016: Journal of Viral Hepatitis
Yusuf Ergün, Muhammed Üremiş, Metin Kılınç, Tuğrul Alıcı
PURPOSE: To evaluated the potential antioxidant agent Legalon (r) SIL (silibinin-C-2',3-bis(hydrogensuccinat)) in the skeletal muscle of rats. METHODS: IRI was achieved via tourniquet application in Wistar-albino rats. Experimental groups were chosen as (i) sham control, (ii) IRI (3+2 h), (iii) IRI and Legalon (r) SIL-50 (50 mg/kg/i.p.), (iv) IRI and Legalon (r) SIL-100 (100 mg/kg/i.p.), and (v) IRI and Legalon (r) SIL-200 (200 mg/kg/ i.p.). Muscle viability (evaluated by triphenyltetrazolium chloride dye method), malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase were assessed in muscle samples using a spectrophotometer...
April 2016: Acta Cirúrgica Brasileira
Anton Gillessen, Wolfgang A Herrmann, Markus Kemper, Helmut Morath, Klaus Mann
BACKGROUND: Many drugs are known to have hepatotoxic side effects. The effect of silymarin on liver function and liver-injury-impaired quality of life under daily practice conditions in patients with elevated values of liver enzymes was evaluated in the present non-interventional study. METHOD: Patients with drug-induced elevated aminotransferase levels and indication for silymarin (Legalon forte) treatment for 2 to 3 months were documented prospectively over 4 months...
December 15, 2014: MMW Fortschritte der Medizin
Abel Felipe Freitag, Gabriel Fernando Esteves Cardia, Bruno Ambrósio da Rocha, Rafael Pazzinatto Aguiar, Francielli Maria de Souza Silva-Comar, Ricardo Alexandre Spironello, Renata Grespan, Silvana Martins Caparroz-Assef, Ciomar Aparecida Bersani-Amado, Roberto Kenji Nakamura Cuman
This study was aimed to investigate the effect of Silymarin (SLM) on the hypertension state and the liver function changes induced by acetaminophen (APAP) in spontaneously hypertensive rat (SHR). Animals normotensive (N) or hypertensive (SHR) were treated or not with APAP (3 g/kg, oral) or previously treated with SLM. Twelve hours after APAP administration, plasmatic levels of liver function markers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), gamma glutamyl transferase (γ-GT), and alkaline phosphatase (ALP) of all groups, were determined...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
S E Fomenko, N F Kushnerova, V G Sprygin, T V Momot
We have studied the effects of the extract from the dry pomace of honeysuckle fruits Lonicera edulis Turcz. and commercial reference preparation Legalon on weight and biochemical liver indexes in rats upon carbon tetrachloride intoxication. The extract of honeysuckle fruits favored a decrease in the total lipid content, reduced specific liver weight, and facilitated restoration of the activity of serum alanine aminotransferase and liver lysosomal enzymes. It the blood of rats, the extract increased superoxide dismutase activity, decreased glutathione level, enhanced antiradical activity, and reduced the level of malonic dialdehyde...
2014: Eksperimental'naia i Klinicheskaia Farmakologiia
Pilar Pais, Massimo D'Amato
INTRODUCTION: A subcategory of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is characterized by accumulation of fat accompanied by inflammatory infiltration and hepatocellular damage. The active complex of milk thistle is a lipophilic extract from its seeds, comprising three isomers, collectively known as silymarin. Silymarin has demonstrated antioxidant, anti-inflammatory, and antifibrotic properties, and has been extensively studied in the treatment of liver diseases...
December 2014: Drugs in R&D
Hélida M L Maranhão, Carlos F B Vasconcelos, Larissa A Rolim, Pedro J Rolim Neto, Jacinto da C Silva Neto, Reginaldo C da Silva Filho, Mariana P Fernandes, João H Costa-Silva, Alice V Araújo, Almir G Wanderley
Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE) on CCl4-induced hepatic damage in rats. SAAE was evaluated by high performance liquid chromatography. The animals were divided into six groups (n = 6/group). Groups I (vehicle-corn oil), II (control-CCl4), III, IV, V and VI were pretreated during 10 consecutive days, once a day p...
October 31, 2014: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
N F Kushnerova, S A Fedoreev, S E Fomenko, V G Sprygin, N I Kulesh, N P Mishchenko, M V Veselova, T V Momot
Hepatoprotective properties of ethanol extract from the roots of Maackia amurensis Ruper et Maxim have been studied on the model of toxic hepatitis induced by carbon tetrachloride damage. It is established that the extract contains daidzein, 7-O-gentobiosides of isoflavonoids genistein, formononetin, pseudobabtige-nin, and 5-O-methylgenistein, and 3-O-gentobiosides of pterocarpans (6aR, 11aR)-maakiain and (6aR, 11aR)-medicarpin. The administration of extract facilitates the restoration of antioxidant protection enzymes activity and reduced glutathione level, decreases the formation of toxic peroxidation products, produces normalizing impact on liver phospholipid pattern, and improves the erythrocyte tolerance to hemolytic agents...
2014: Eksperimental'naia i Klinicheskaia Farmakologiia
Janela McClure, Daciana H Margineantu, Ian R Sweet, Stephen J Polyak
In this report, we further characterized the effects of silibinin (SbN), derived from milk thistle extract, and Legalon-SIL (SIL), a water-soluble derivative of SbN, on T cell metabolism and HIV infection. We assessed the effects of SbN and SIL on peripheral blood mononuclear cells (PBMC) and CEM-T4 cells in terms of cellular growth, ATP content, metabolism, and HIV infection. SIL and SbN caused a rapid and reversible (upon removal) decrease in cellular ATP levels, which was associated with suppression of mitochondrial respiration and glycolysis...
January 20, 2014: Virology
Federica Sala, Pablo Albares, Milena Colovic, Stefano Persiani, Lucio C Rovati
To investigate the pharmacokinetics of silibinin and silibinin hemisuccinate in human plasma, two high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods were developed and validated. The methods require a small volume of sample (100μL), and the recovery of the analytes was complete with a good reproducibility (CV% 1.7-9.5), after a simple protein precipitation. Naringenin was used as internal standard. The chromatographic methods provided a good separation of diastereoisomers A and B of both silibinin and silibinin hemisuccinate onto a Chromolith Performance RP18e 100mm×3mm column, with a resolution of peaks from plasma matrix in less than 6min...
January 15, 2014: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Mingzhu Shangguan, Yi Lu, Jianping Qi, Jin Han, Zhiqiang Tian, Yunchang Xie, Fuqiang Hu, Hailong Yuan, Wei Wu
The main purpose of this study was to prepare binary lipids-based nanostructured lipid carriers to improve the oral bioavailability of silymarin, a poorly water-soluble liver protectant. Silymarin-loaded nanostructured lipid carriers were prepared by the method of high-pressure homogenization with glycerol distearates (Precirol ATO-5) and oleic acid as the solid and liquid lipids, respectively, and lecithin (Lipoid E 100) and Tween-80 as the emulsifiers. The silymarin-nanostructured lipid carrier prepared under optimum conditions was spherical in shape with mean particle size of ∼78...
February 2014: Journal of Biomaterials Applications
Paula Cordero-Pérez, Liliana Torres-González, Marcelino Aguirre-Garza, Carlos Camara-Lemarroy, Francisco Guzmán-de la Garza, Gabriela Alarcón-Galván, Homero Zapata-Chavira, Ma de Jesús Sotelo-Gallegos, Cipactli Nadjedja Torres-Esquivel, Ethel Sánchez-Fresno, Daniel Cantú-Sepúlveda, Gerardo González-Saldivar, Judith Bernal-Ramirez, Linda E Muñoz-Espinosa
BACKGROUND: Various hepatoprotective herbal products from plants are available in Mexico, where up to 85% of patients with liver disease use some form of complementary and alternative medicine. However, only few studies have reported on the biological evaluation of these products. OBJECTIVE: Using a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, we evaluated the effects of commercial herbal extracts used most commonly in the metropolitan area of Monterrey, Mexico...
July 2013: Pharmacognosy Research
Marjan Gharagozloo, Mehran Karimi, Zahra Amirghofran
OBJECTIVE: Silymarin, a flavonolignan complex isolated from milk thistle, is a cytoprotective, antioxidant, and hepatoprotective agent. The present study was designed to investigate the immunomodulatory effects of orally administered silymarin in patients with β-thalassemia major. METHODS: The immunomodulatory effects of silymarin were investigated in a 12-week clinical trial in two groups of patients. In combined therapy group (n=25), patients continued desferrioxamine at the dose of 40mg/kg/day and Legalon® tablets (420mg daily) were added to desferrioxamine...
June 2013: International Immunopharmacology
Behjat Moayedi, Marjan Gharagozloo, Nafiseh Esmaeil, Mohammad R Maracy, Hamid Hoorfar, Mohsen Jalaeikar
OBJECTIVE: Thalassemia is one of the most common genetic disorders worldwide. Chronic blood transfusions treat the underlying anemia but may lead to iron toxicity. Effective iron chelation remains one of the main targets of clinical management of thalassemia major. In this study, iron-chelating activity of silymarin, a flavonolignan isolated from silybum marianum, was examined in β-thalassemia major. METHODS: Patients were treated with the combination of desferrioxamine and silymarin (Legalon(®) ; n = 49) or desferrioxamine plus placebo (n = 48) for 9 months...
March 2013: European Journal of Haematology
Naira J N Brito, Jorge A López, Maria Aparecida do Nascimento, José B M Macêdo, Gabriel Araujo Silva, Cláudia N Oliveira, Adriana Augusto de Rezende, José Brandão-Neto, Aline Schwarz, Maria das Graças Almeida
The present study aimed to determine whether the leaves of Turnera ulmifolia Linn. var. elegans extract exert significant antioxidant activity. The antioxidant activity of its hydroethanolic extract (HEETU) was evaluated by assessing (a) its radical scavenging ability in vitro, and (b) its in vivo effect on lipid peroxidation and antioxidant enzyme activities. The in vitro antioxidant assay (DPPH) clearly supported HEETU free radical scavenging potential. Moreover, glutathione content and antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase and catalase) were significantly enhanced in CCl(4)-treated rats due to oral HEETU-treatment (500 mg/kgb...
December 2012: Food and Chemical Toxicology
Bryan J Brinda, Hao-Jie Zhu, John S Markowitz
Silymarin, an extract of crushed achenes of the milk thistle plant Silybum marianum is a multi-constituent mixture, 70-80% of which consists of a complex assortment containing the flavonolignans silybin A and B, isosilybin A and B, silydianin, and silychristin, and the flavonoid taxifolin. To date, numerous pharmacological actions of the silymarin extract have been documented in the biomedical literature, including hepatoprotective, anti-inflammatory, anti-tumor, and anti-fibrotic activities. The present study describes a novel liquid chromatographic-tandem mass spectrometric method for simultaneous analysis of silychristin, silydianin, silybin A and silybin B, isosilybin A and isosilybin B, and taxifolin in human plasma employing liquid-liquid extraction...
August 1, 2012: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Ulrich Mengs, Ralf-Torsten Pohl, Todd Mitchell
More than 90% of all fatal mushroom poisonings worldwide are due to amatoxin containing species that grow abundantly in Europe, South Asia, and the Indian subcontinent. Many cases have also been reported in North America. Initial symptoms of abdominal cramps, vomiting, and a severe cholera-like diarrhea generally do not manifest until at least six to eight hours following ingestion and can be followed by renal and hepatic failure. Outcomes range from complete recovery to fulminant organ failure and death which can sometimes be averted by liver transplant...
August 2012: Current Pharmaceutical Biotechnology
Jeremie Guedj, Harel Dahari, Ralf T Pohl, Peter Ferenci, Alan S Perelson
BACKGROUND & AIMS: Legalon® SIL (SIL) is a chemically hydrophilized version of silibinin that has exhibited high antiviral effectiveness against hepatitis C virus (HCV). Its main mode of action (MOA) remains unclear, with contradicting in vitro studies supporting either suppression of entry and cell-to-cell spread or suppression of viral RNA synthesis as the main MOA. We sought to provide new insights into SIL's MOA in HCV genotype-1/4 patients receiving intravenous SIL monotherapy for 7 days via mathematical modeling...
May 2012: Journal of Hepatology
Karoline Rutter, Thomas-Matthias Scherzer, Sandra Beinhardt, Heidrun Kerschner, Albert F Stättermayer, Harald Hofer, Theresia Popow-Kraupp, Petra Steindl-Munda, Peter Ferenci
BACKGROUND: Intravenous silibinin (ivSIL) is a potent antiviral agent against HCV. In vitro silibinin (SIL) inhibits viral replication, possibly by inhibiting HCV RNA polymerase. In this proof-of-concept study, ivSIL was tested in on-treatment non-responders to full-dose of pegylated interferon-α2a/ribavirin (standard of care [SOC]). METHODS: A total of 27 treatment-naive patients with <2 log drop in viral load after 12 weeks or still detectable HCV RNA after 24 weeks of SOC treatment (mean age 54...
2011: Antiviral Therapy
Ruyue Lian, Yi Lu, Jianping Qi, Yanan Tan, Mengmeng Niu, Peipei Guan, Fuqiang Hu, Wei Wu
Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle, is used clinically as a hepatoprotector to treat liver injuries and chronic hepatitis. However, its therapeutic effect is compromised by its poor oral bioavailability due to the poor solubility and low permeability across intestinal epithelia. The main purpose of this study was to prepare silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) to improve the oral bioavailability of silymarin. GMO/P407 LCMs were prepared by a melting/congealing method...
December 2011: AAPS PharmSciTech
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