Silibinin Is a Potent Antiviral Agent in Patients With Chronic Hepatitis C Not Responding to Pegylated Interferon/Ribavirin Therapy

Ferenci, Péter; Scherzer, Thomas–Matthias; Kerschner, Heidrun; Rutter, Karoline; Beinhardt, Sandra; Hofer, Harald; Schöniger–Hekele, Maximilian; Holzmann, Heidemarie; Steindl–Munda, Petra

doi:10.1053/j.gastro.2008.07.072

Cited by 212 publications

(186 citation statements)

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“…In our animal model, silibinin was able to decrease both isoprostanes, which are sensitive markers of lipoperoxidation [29], and 8-OHG, a marker of DNA damage, which is increased in NAFLD patients in relation to degree of liver injury [30] and in patients with obesity/diabetes cardiomyopathy [17]. The used dose is higher than in the commercially available oral formulations of silymarin/silibinin, but the safety for comparable dosage of silibinin has been showed both in healthy volunteers [31] and in patients with chronic liver disease [32,33]. Previous findings reported the efficacy of a silibinin/vitamin E oral formulation on surrogate serum markers of liver injury in NAFLD patients [34] and the inhibitory effect of silibinin on human hepatic stellate cells activation in vitro [35].…”

Section: Discussionmentioning

confidence: 99%

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Salamone¹,

Galvano²,

Marino³

et al. 2012

Digestive and Liver Disease

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a b s t r a c tBackground: Nonalcoholic fatty liver disease is a chronic metabolic disorder with significant impact on cardiovascular and liver mortality. Aims: In this study, we examined the effects of silibinin on liver and myocardium injury in an experimental model of nonalcoholic fatty liver disease. Methods: A four-week daily dose of silibinin (20 mg/kg i.p.) was administrated to db/db mice fed a methionine-choline deficient diet. Hepatic and myocardial histology, oxidative stress and inflammatory cytokines were evaluated. Results: Silibinin administration decreased HOMA-IR, serum ALT and markedly improved hepatic and myocardial damage. Silibinin reduced isoprostanes, 8-deoxyguanosine and nitrites/nitrates in the liver and in the heart of db/db fed the methionine-choline deficient diet, whereas glutathione levels were restored to lean mice levels in both tissues. Consistently, liver mitochondrial respiratory chain activity was significantly impaired in untreated mice and was completely restored in silibinin-treated animals. TNF-␣ was increased whereas IL-6 was decreased both in the liver and heart of db/db fed methionine-choline deficient diet. Silibinin reversed heart TNF-␣ and IL-6 expression to control mice levels. Indeed, liver JNK phosphorylation was reduced to control levels in treated animals. Conclusions: This study demonstrates a combined effectiveness of silibinin on improving liver and myocardial injury in experimental nonalcoholic fatty liver disease.

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Section: Discussionmentioning

confidence: 99%

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Salamone¹,

Galvano²,

Marino³

et al. 2012

Digestive and Liver Disease

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“…52 Second, the liberal use of poorly standardized crude extracts or complex mixtures of botanicals poses an increased risk of hepatotoxicity. 54 As a result, only a few botanicals are currently in recognized clinical trials, including the flavonoids silymarin or silibinin from milk thistle for patients with chronic hepatitis C or nonalcoholic steatohepatitis 55 (see http://clinicaltrials-.gov/ for a complete list). Drug Repositioning.…”

Section: Antifibrotic Drug Developmentmentioning

confidence: 99%

Targeting liver fibrosis: Strategies for development and validation of antifibrotic therapies

2009

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We have made striking progress in our understanding of the biochemistry and cell biology that underlies liver fibrosis and cirrhosis, including the development of strategies and agents to prevent and reverse fibrosis. However, translation of this knowledge into clinical practice has been hampered by (1) the limitation of many in vitro and in vivo models to confirm mechanisms and to test antifibrotic agents, and (2) the lack of sensitive methodologies to quantify the degree of liver fibrosis and the dynamics of fibrosis progression or reversal in patients. Furthermore, whereas cirrhosis and subsequent decompensation are accepted hard clinical endpoints, fibrosis and fibrosis progression alone are merely plausible surrogates for future clinical deterioration. In this review we focus on an optimized strategy for preclinical antifibrotic drug development and highlight the current and future techniques that permit noninvasive assessment and quantification of liver fibrosis and fibrogenesis. The availability of such noninvasive methodologies will serve as the pacemaker for the clinical development and validation of potent antifibrotic agents. (HEPATOLOGY 2009;50:1294-1306

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“…Although its clinical efficacy is currently uncertain (8,10), interest in this botanical medicine has been piqued by studies showing silymarin blocks HCV cell culture (HCVcc) infection (9). Intravenous administration of silibinin, composed of a 1:1 mixture of silybin A and silybin B, causes dose-dependent reduction of viral load in patients with chronic hepatitis C (11).…”

mentioning

confidence: 99%

Identification of hepatoprotective flavonolignans from silymarin

Polyak

Morishima

Lohmann

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

282

217

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Silymarin, also known as milk thistle extract, inhibits hepatitis C virus (HCV) infection and also displays antioxidant, anti-inflammatory, and immunomodulatory actions that contribute to its hepatoprotective effects. In the current study, we evaluated the hepatoprotective actions of the seven major flavonolignans and one flavonoid that comprise silymarin. Activities tested included inhibition of: HCV cell culture infection, NS5B polymerase activity, TNF-α-induced NF-κB transcription, virus-induced oxidative stress, and T-cell proliferation. All compounds were well tolerated by Huh7 human hepatoma cells up to 80 μM, except for isosilybin B, which was toxic to cells above 10 μM. Select compounds had stronger hepatoprotective functions than silymarin in all assays tested except in T cell proliferation. Pure compounds inhibited JFH-1 NS5B polymerase but only at concentrations above 300 μM. Silymarin suppressed TNF-α activation of NF-κB dependent transcription, which involved partial inhibition of IκB and RelA/p65 serine phosphorylation, and p50 and p65 nuclear translocation, without affecting binding of p50 and p65 to DNA. All compounds blocked JFH-1 virus-induced oxidative stress, including compounds that lacked antiviral activity. The most potent compounds across multiple assays were taxifolin, isosilybin A, silybin A, silybin B, and silibinin, a mixture of silybin A and silybin B. The data suggest that silymarin-and silymarin-derived compounds may influence HCV disease course in some patients. Studies where standardized silymarin is dosed to identify specific clinical endpoints are urgently needed.hepatitis C | liver disease | milk thistle | botanical medicine | hepatoprotection C hronic hepatitis C virus (HCV) is a major global medical problem. In the United States, millions of people are affected, the number of patients with HCV-induced end-stage liver disease is growing (1), and this condition is already the leading indication for liver transplantation (2). The current standard of care for chronic hepatitis C, pegylated IFN-α and ribavirin, results in sustained elimination of virus in 55% of treated patients (3, 4). However, significant numbers of patients do not clear the virus and are intolerant to, have contraindications to, or opt out of therapy. Furthermore, because emerging specifically targeted antiviral therapy for HCV therapies need to be administered with pegylated IFN plus ribavirin (5), it is likely that many patients will not tolerate this therapy. Thus, there are many patients who have no other Food and Drug Administration-approved options to eliminate HCV and prevent progression of liver disease. As a result, many individuals have opted for complementary and alternative medicine-based approaches, including botanicals, to treat their chronic hepatitis C. Indeed, as many as 13 to 23% of American patients with chronic liver disease use botanical medicines, with silymarin being the most popular (6, 7).Silymarin, an extract from the seeds of the milk thistle plant, Silybum marianum, has been used fo...

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Silibinin Is a Potent Antiviral Agent in Patients With Chronic Hepatitis C Not Responding to Pegylated Interferon/Ribavirin Therapy

Cited by 212 publications

References 25 publications

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Targeting liver fibrosis: Strategies for development and validation of antifibrotic therapies

Identification of hepatoprotective flavonolignans from silymarin

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