Silymarin Ascending Multiple Oral Dosing Phase I Study in Noncirrhotic Patients With Chronic Hepatitis C

Hawke, Roy L.; Schrieber, Sarah J.; Soule, Tedi A.; Zhao, Wen; Smith, Philip C.; Reddy, K. Rajender; Wahed, Abdus S.; Belle, Steven H.; Afdhal, Nezam H.; Navarro, Victor J.; Berman, Josh; Liu, Qi‐Ying; Doo, Edward; Fried, Michael

doi:10.1177/0091270009347475

Cited by 131 publications

(150 citation statements)

References 38 publications

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“…Chronic inflammation occurs in patients with hepatic damage. Thus, for patients with compensatory cirrhosis, hepatitis C, and non-alcoholic hepatic steatosis, the bioavailability of compounds present in silymarin may be affected, which may also explain the low effectiveness of treatment with flavonoids in these patients [12,13] . Sy-Cordero et al [14] isolated four key flavolignans and diastereoisomers (silybin A, silybin B, isosilybin A, and isosilybin B) from S. marianum on a gram-scale.…”

Section: Overviewmentioning

confidence: 99%

Hepatoprotective effect of silymarin

Vargas-Mendoza

Madrigal-Santillán

Morales-González

et al. 2014

WJH

332

171

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The use of medicinal plants in treating illnesses has been reported since ancestral times. In the case of hepatic diseases, several species such as Silybum marianum , Phyllanthus niruri, and Panus giganteus (Berk.) have been shown to ameliorate hepatic lesions. Silymarin is a natural compound derived from the species Silybum marianum , which is commonly known as Milk thistle. This plant contains at least seven flavoligands and the flavonoid taxifolin. The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol, acetaminophen, and carbon tetrachloride. The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation. Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver. It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity. A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Silybum marianum ; Hepatoprotector; Lipoperoxidation; Silymarin Core tip: One of the mechanisms of liver damage caused by alcohol is the generation of free radicals formed by the metabolism of this xenobiotic. Silymarin is an antioxidant that protects the liver from the free radical damage produced by alcohol metabolism. Silymarin is the most used natural compound for the treatment of hepatic diseases worldwide due to its antioxidant, anti-inflammatory, and anti-fibrotic activities. Silymarin functions by stabilizing biological membranes and increasing protein synthesis.

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Section: Overviewmentioning

confidence: 99%

Hepatoprotective effect of silymarin

Vargas-Mendoza

Madrigal-Santillán

Morales-González

et al. 2014

WJH

332

171

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“…It has been shown that HCV modifies antioxidant defense mechanisms yielding a cellular oxidative imbalance [29,31,41] . Several authors, including our research group, have demonstrated that HCV effectively modifies gene expression regulatory proteins of oxidative stress as SOD and catalase [26,31,33] .…”

Section: Antioxidant Therapymentioning

confidence: 99%

“…As an example a phase Ⅰ trial assessing the efficacy of oral doses of silymarin in non-responders HCV infected patients demonstrated no adverse effects but also showed no antiviral efficacy against HCV [41] . However, in other report the administration of intravenous (iv) silibilin in non-responders HCV infected patients decreased HCV-RNA levels in a dose-dependent manner [58] .…”

Section: Silymarin Complexmentioning

confidence: 99%

Oxidative stress modulation in hepatitis C virus infected cells

Lozano-Sepúlveda

Bryan-Marrugo

Córdova-Fletes

et al. 2015

WJH

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“…We have previously reported on the ascending multiple dose pharmacokinetics of silymarin in noncirrhotic patients with chronic HCV infection (Hawke et al, 2010) obtained from a double-blind, placebocontrolled phase 1 trial that was conducted in patients with either HCV or NAFLD. An unexpected finding was that dose proportionality in the pharmacokinetics of parent silymarin flavonolignans was not observed in HCV patients with well compensated liver disease at silymarin doses greater than 560 mg when administered orally every 8 h (Hawke et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Differences in the Disposition of Silymarin between Patients with Nonalcoholic Fatty Liver Disease and Chronic Hepatitis C

Schrieber¹,

Hawke²,

Zhao³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Silymarin, derived from the milk thistle plant Silybum marianum and widely used for self-treatment of liver diseases, is composed of six major flavonolignans including silybin A and silybin B, which are the predominant flavonolignans quantified in human plasma. The single-and multiple-dose pharmacokinetics of silymarin flavonolignans were examined in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis C virus (HCV) to determine whether the disposition of silymarin and therefore its potential efficacy vary among liver disease populations. Cohorts of eight subjects with noncirrhotic liver disease were randomized 3:1 to oral silymarin or placebo (280 or 560 mg) every 8 h for 7 days. Forty-eight-hour blood sampling was conducted after the first and final doses. In general, plasma concentrations of silybin A and silybin B were higher, whereas concentrations of conjugates were lower in NAFLD compared with HCV. After adjustment of the area under plasma concentration-time curve from 0 to 8 h (AUC 0-8 h ) for weight and dose, only silybin B and silybin B conjugates differed significantly between disease types. For NAFLD, the adjusted mean AUC 0-8 h was higher for silybin B (p < 0.05) but lower for silybin B conjugates (p < 0.05) compared with that for HCV. At the 280-mg dose, steady-state plasma concentrations of silybin B conjugates for NAFLD subjects were characterized by 46% lower AUC 0-8 h (p < 0.05) and 42% lower C max (p < 0.05) compared with HCV subjects. Evidence of enterohepatic cycling of flavonolignans was only observed in NAFLD subjects. In summary, the efficacy of silymarin may be more readily observed in NAFLD patients because of their higher flavonolignan plasma concentrations and more extensive enterohepatic cycling compared with those in HCV patients.

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Silymarin Ascending Multiple Oral Dosing Phase I Study in Noncirrhotic Patients With Chronic Hepatitis C

Cited by 131 publications

References 38 publications

Hepatoprotective effect of silymarin

Hepatoprotective effect of silymarin

Oxidative stress modulation in hepatitis C virus infected cells

Differences in the Disposition of Silymarin between Patients with Nonalcoholic Fatty Liver Disease and Chronic Hepatitis C

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