Toward the Definition of the Mechanism of Action of Silymarin: Activities Related to Cellular Protection From Toxic Damage Induced by Chemotherapy

Comelli, Maria Cristina; Mengs, U.; Schneider, Carl Christoph; Prosdocimi, Marco

doi:10.1177/1534735407302349

Cited by 118 publications

(91 citation statements)

References 56 publications

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“…Evidence in support of both modes of action was provided in the present study. These data extend silymarin's previously documented antioxidant functions (28) to the context of HCV infection. Because silymarin inhibits oxidative stress independently of suppression of virus, it is possible that the hepatoprotective actions of the botanical may be extended to liver diseases of nonviral origin.…”

Section: Discussionsupporting

confidence: 69%

“…Although silibinin, which is a mixture of silybin A and silybin B, has been largely touted to contain many of the hepatoprotective functions (28,29), we are unique in showing that there are other flavonolignans in silymarin that are equal to, if not more potent, than silibinin. The best examples are isosilybin A and taxifolin, which have antiviral activities that were superior to silibinin.…”

Section: Discussionmentioning

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.

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: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Identification of hepatoprotective flavonolignans from silymarin

Polyak

Morishima

Lohmann

et al. 2010

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

282

217

View full text Add to dashboard Cite

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“…The differences in the AST and ALT reductions were statistically significant. Therefore, the combination of silymarin with such potentially hepatotoxic drugs may prevent such adverse reactions (Comelli et al, 2007).…”

Section: Toxic and Iatrogenic Liver Diseasementioning

confidence: 99%

Milk thistle in liver diseases: past, present, future

Abenavoli

Capasso²,

Milić

et al. 2010

Phytotherapy Research

489

350

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Silybum marianum or milk thistle (MT) is the most well‐researched plant in the treatment of liver disease. The active complex of MT is a lipophilic extract from the seeds of the plant and is composed of three isomer flavonolignans (silybin, silydianin, and silychristin) collectively known as silymarin. Silybin is a component with the greatest degree of biological activity and makes up 50% to 70% of silymarin. Silymarin is found in the entire plant but it is concentrated in the fruit and seeds. Silymarin acts as an antioxidant by reducing free radical production and lipid peroxidation, has antifibrotic activity and may act as a toxin blockade agent by inhibiting binding of toxins to the hepatocyte cell membrane receptors. In animals, silymarin reduces liver injury caused by acetaminophen, carbon tetrachloride, radiation, iron overload, phenylhydrazine, alcohol, cold ischaemia and Amanita phalloides. Silymarin has been used to treat alcoholic liver disease, acute and chronic viral hepatitis and toxin‐induced liver diseases. Copyright © 2010 John Wiley & Sons, Ltd.

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“…The main isomeric flavonoids of SIL are silydianin, silychristine, silibinin and isosilibinin (Comelli et al, 2007). It is widely used for the treatment of different symptoms including jaundice, hepatitis and cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

Inulin nanoparticles and silymarin counteract chlorpromazine-induced injury in the liver and kidney of rats

Abdel-Wahhab¹,

Eid²,

Ahmed³

et al. 2017

J App Pharm Sci

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The aim of the current study was to evaluate the protective role of inulin nanoparticles (INPs) prepared by the emulsion method alone or plus silymarin (SIL) against chlorpromazine (CPZ)-induced hepatonephrotoxicity in rats. Eleven groups of female Sprague-Dawley rats were treated orally for 3 weeks as follow: control group, the group treated with CPZ (38.7 mg/kg. b.w in 1 ml saline each 72 h), the groups treated with INPs at low (100 mg/kg b.w) or high (200 mg/ kg b.w) dose, the group treated with SIL (50 mg/kg b.w), the groups treated with SIL plus INPs at the two doses and the groups treated with CPZ plus SIL and INPs at the two tested doses. At the end of the treatment period, blood and tissue samples were collected for different biochemical and histological analyses. The results indicated that CPZ induced significant disturbances in liver and kidney function indices, oxidative stress markers, lipid profile, antioxidant enzyme activity and DNA fragmentation as well as the histological changes in the liver and kidney. SIL alone or plus INPs alone at the low or high dose induce insignificant changes in all the tested parameters or pathological changes in the liver and kidney. SIL and INPs at the two doses could induce a pronounced protection in liver and kidney of CPZ-treated animals due to their antioxidant activity and the role of INPs in the enhancement of SIL solubility. It could be concluded that INPs is a promise drug delivery for SIL and could prevent the liver and kidney injury induced by CPZ.

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Toward the Definition of the Mechanism of Action of Silymarin: Activities Related to Cellular Protection From Toxic Damage Induced by Chemotherapy

Cited by 118 publications

References 56 publications

Identification of hepatoprotective flavonolignans from silymarin

Identification of hepatoprotective flavonolignans from silymarin

Milk thistle in liver diseases: past, present, future

Inulin nanoparticles and silymarin counteract chlorpromazine-induced injury in the liver and kidney of rats

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