Inhibition of T-Cell Inflammatory Cytokines, Hepatocyte NF-κB Signaling, and HCV Infection by Standardized Silymarin

Polyak, Stephen J.; Morishima, Chihiro; Shuhart, Margaret C.; Wang, Chia C.; Liu, Yanze; Lee, David Y.W.

doi:10.1053/j.gastro.2007.02.038

Cited by 211 publications

(188 citation statements)

References 83 publications

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“…Silymarin blocks NF-κB-dependent transcription from a canonical NF-κB promoter (9). Silymarin also blocked TNF-α activation of NF-κB dependent transcription from the positive regulatory domain (pRDII) domain of the IFN-B promoter, a key gene in antiviral defense (21) (Fig.…”

Section: Resultsmentioning

confidence: 89%

“…We previously showed that silymarin blocked HCVcc infection of human hepatoma cultures, inhibited TNF-α and TCR induced NFκB-dependent transcription, and suppressed TCR-mediated proliferation and inflammatory cytokine production from T cells (9,12). Thus, silymarin displays antiviral, anti-inflammatory, and immunomodulatory functions in human liver and immune cells.…”

mentioning

confidence: 97%

“…Although silymarin has been described to possess antioxidant, immunomodulatory, antiproliferative, antifibrotic, and antiviral activities (8,9), its mechanisms of action remain to be fully defined. 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).…”

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confidence: 99%

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Identification of hepatoprotective flavonolignans from silymarin

Polyak

Morishima

Lohmann

et al. 2010

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

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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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Section: Resultsmentioning

confidence: 89%

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confidence: 97%

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confidence: 99%

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Identification of hepatoprotective flavonolignans from silymarin

Polyak

Morishima

Lohmann

et al. 2010

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

Self Cite

282

217

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“…Silymarin's hepatoprotective effects are accomplished via several mechanisms including antioxidation, free radical scavenging properties and stabilisation of cell membrane [20,21,24,27], inhibition of lipid peroxidation [28,29], protection of glutathione depletion [30]. Recently, studies have shown silymarin exhibits several anti-inflammatory effects [31,32]. Silymarin has also promotes hepatic tissue regeneration through increasing hepatocyte protein synthesis [33].…”

Section: Resultsmentioning

confidence: 99%

Total Polyphenolic Content and Antioxidant Activity of Silybum Marianum Cultures Grown on Different Growth Regulators

Mekky

Sohafy

El-khair

et al. 2017

Int J Pharm Pharm Sci

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Objective: The present study was designed to study the effect of supplementing Silybum marianum cultures with different combinations and concentrations of growth regulators on the total phenolic content and the antioxidant activity of the produced cultures. Methods:The total polyphenolic content of 23 extracts of calli was calculated as µg of gallic acid/mg of dry weight extract (DWE) using FolinCiocalteu reagent. The antioxidant activity was calculated as trolox equivalent antioxidant capacity using 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) assay for extracts containing more than 10 µg gallic acid/mg DWE.Results: Most of the combinations showed an increase in the total polyphenolic concentration compared to the wild plant. However, cultures grown on media supplemented with combinations of benzyl aminopurine (BAP) and gebberellic acid (Gb), adenine (Ad) and kinetin (Kin), BAP and indole acetic acid (IAA) possessed the highest total polyphenolic contents 20.5, 13.09 and 12.15 µg gallic acid/mg DWE, respectively. However, only (BAP+Gb), (BAP+1-Naphthaleneacetic acid (NAA), IAA, kin and (BAP+Ad) showed a significant increase in the antioxidant activity calculated as trolox equivalent with 2.65, 1.56, 1.56, 1.35 and 1.22 folds increase over the wild plant, respectively. Conclusion:The results obtained clearly indicated that changing the growth regulator system of Silybum marianum cultures serves as an easy and reliable method for increasing the total phenolic content and the antioxidant activity of cultures.

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“…In another study, Polyak et al 17 suggested that silymarin exerted anti-inflammatory and antiviral effects, and it might assist in the management of patients with chronic hepatitis C.…”

Section: Discussionmentioning

confidence: 99%

Effect of sılymarın on oxıdatıve stress and lıver hıstopathology ın experımental obstructıve jaundıce model

Onalan¹,

Tuncal²,

Kılıçoğlu³

et al. 2016

Acta Cir. Bras.

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PURPOSE:To investigate the effect of silymarin on oxidative stress and hepatic injury induced by obstructive jaundice in an experimental model. METHODS:Thirty Wistar-Albino type female rats were divided into 3 groups each including 10 rats. Only laparotomy was performed in group 1. Bile duct ligation was performed in group 2. In group 3, bile duct ligation was performed and orogastic silymarin 300 mg/ kg/day dose was given for seven days. At the end of seven days, rats were sacrificed. The blood and liver tissue samples were taken to be examined biochemically and histopathologically. RESULTS:The plasma and liver levels of malondialdehyde were significantly lower in silymarin group than in the bile duct ligated group. Although liver levels of GSH were significantly higher in silymarin group than in the bile duct ligated group, there was no significant difference between the plasma GSH levels of these groups. In silymarin group; the enlargement of hepatocytes, dilatation of canaliculi and the edema were regressed. CONCLUSION:Silymarin diminished the harmful effects of obstructive jaundice on liver.

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Inhibition of T-Cell Inflammatory Cytokines, Hepatocyte NF-κB Signaling, and HCV Infection by Standardized Silymarin

Cited by 211 publications

References 83 publications

Identification of hepatoprotective flavonolignans from silymarin

Identification of hepatoprotective flavonolignans from silymarin

Total Polyphenolic Content and Antioxidant Activity of Silybum Marianum Cultures Grown on Different Growth Regulators

Effect of sılymarın on oxıdatıve stress and lıver hıstopathology ın experımental obstructıve jaundıce model

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