Silymarin: A Review of its Clinical Properties in the Management of Hepatic Disorders

Wellington, Keri; Jarvis, Blair

doi:10.2165/00063030-200115070-00005

Cited by 412 publications

(291 citation statements)

References 32 publications

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“…Similar or possibly identical transport mechanism inhibited by silibinin was described for amanitin (Wellington and Jarvis, 2001). Therefore, silymarin is able to reduce the cellular absorption of noxious xenobiotics other than mushroom poisons, thereby exerting cell-protection.…”

Section: Phalloidin (A Bicyclic Heptapeptide) and Antamanide (A Monocsupporting

confidence: 66%

Milk thistle in liver diseases: past, present, future

Abenavoli

Capasso²,

Milić

et al. 2010

Phytotherapy Research

503

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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Section: Phalloidin (A Bicyclic Heptapeptide) and Antamanide (A Monocsupporting

confidence: 66%

Milk thistle in liver diseases: past, present, future

Abenavoli

Capasso²,

Milić

et al. 2010

Phytotherapy Research

503

350

View full text Add to dashboard Cite

show abstract

“…Silymarin possesses hepatoprotective properties and has been widely used for decades to treat patients with liver disease (8). Recent studies have shown that silibinin and silymarin inhibits growth of many cancers including breast, lung, colon, pancreas, and prostate cancer cells (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Combined Treatment with Silibinin and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Overcomes Drug Resistance Caused by T790M Mutation

Rho

Choi

Jeon

et al. 2010

Molecular Cancer Therapeutics

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Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) produce an initially dramatic response in lung cancer patients harboring a mutation in the EGFR gene, development of acquired resistance is almost inevitable. A secondary mutation of threonine 790 (T790M) is associated with approximately half of the cases of acquired resistance. This study investigated whether the addition of silibinin to therapy with gefitinib or erlotinib could overcome T790M-mediated drug resistance considering that silibinin has various antitumor effects, including EGFR modulation. Silibinin selectively reduced the activity of the EGFR family (EGFR, ErbB2, and ErbB3) through the inhibition of receptor dimerization in lung cancer cells with EGFR mutations, but not in those harboring the wild type. In primary and acquired resistant cells with T790M, addition of silibinin enhanced the ability of EGFR-TKIs to downregulate EGFR signals and to inhibit cell growth. Similarly, the combination of silibinin and erlotinib effectively suppressed tumor growth in erlotinib resistance-bearing PC-9 xenografts. The results indicate that the addition of silibinin to EGFR-TKIs is a promising strategy to overcome T790M-mediated drug resistance. Mol Cancer Ther; 9(12); 3233-43. Ó2010 AACR.

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“…seeds, and is widely known for its hepatoprotective and cancer chemopreventive action (Wellington and Jarvis, 2001;Agarwal, 2002, 2006;Deep et al, 2006). Recently, we have isolated and purified from silymarin seven distinct flavonolignans namely silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, isosilychristin and one flavonoid taxifolin ; and assessed their biological effects on many antiproliferative end points in human PCA cell lines (Davis-Searles et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Isosilybin B causes androgen receptor degradation in human prostate carcinoma cells via PI3K-Akt-Mdm2-mediated pathway

et al. 2008

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The identification and development of novel nontoxic phytochemicals that target androgen and androgen receptor (AR) signaling remains a priority for prostate cancer (PCA) control. In the present study, we assessed the antiandrogenic efficacy of isosilybin B employing human PCA LNCaP (mutated AR), 22Rv1 (mutated AR) and LAPC4 (wild-type AR) cells. Isosilybin B (10-90 lM) treatment decreased the AR and prostate specific antigen (PSA) levels in LNCaP, 22Rv1 and LAPC4 cells, but not in non-neoplastic human prostate epithelial PWR-1E cells. Isosilybin B treatment also inhibited synthetic androgen R1881-induced nuclear localization of AR, PSA expression and cell growth, and caused G 1 arrest. In mechanistic studies identifying AR degradation, isosilybin B caused increased phosphorylation of Akt (Ser-473 and Thr-308) and Mdm2 (Ser-166), which was linked with AR degradation as pretreatment with PI3K inhibitor (LY294002)-restored AR level. Further, overexpression of kinase-dead Akt largely reversed isosilybin B mediated-AR degradation suggesting a critical role of Akt in AR degradation. Antibody pull-down results also indicated that isosilybin B treatment enhances the formation of complex between Akt, Mdm2 and AR, which promotes phosphorylation-dependent AR ubiquitination and its degradation by proteasome. Together, present findings identify a novel mechanism for isosilybin B-mediated anticancer effects in human PCA cells.

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Silymarin: A Review of its Clinical Properties in the Management of Hepatic Disorders

Cited by 412 publications

References 32 publications

Milk thistle in liver diseases: past, present, future

Milk thistle in liver diseases: past, present, future

Combined Treatment with Silibinin and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Overcomes Drug Resistance Caused by T790M Mutation

Isosilybin B causes androgen receptor degradation in human prostate carcinoma cells via PI3K-Akt-Mdm2-mediated pathway

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