SILYMARIN (MILK THISTLE 80%EXT)
Silybin and silymarin--new and emerging applications in medicine
1: Curr Med Chem. 2007;14(3):315-38.
Silybin and silymarin--new and emerging applications in medicine.
Laboratory of Biotransformation, Institute of Microbiology, Academy of Sciences of the Czech Republic, Videzska 1083, CZ-142 20 Prague, Czech Republic.
This review critically surveys the literature published mainly within this millennium on the new and emerging applications of silybin (pure, chemically defined substance) and silymarin (flavonoid complex from Silybum marianum - milk thistle seeds). These compounds used so far mostly as hepatoprotectants were shown to have other interesting activities, e.g. anticancer and canceroprotective and also hypocholesterolemic activity. These effects were demonstrated in a large variety of illnesses of different organs, e.g. prostate, lungs, CNS, kidneys, pancreas and also in the skin protection. Besides the cytoprotective activity of silybin mediated by its antioxidative and radical-scavenging properties also new functions based on the specific receptor interaction were discovered. These were studied on the molecular level and modulation of various cell-signaling pathways with silybin was disclosed--e.g. NF-kappaB, inhibition of EGFR-MAPK/ERK1/2 signaling, activity upon Rb and E2F proteins, IGF-receptor signaling. Proapoptotic activity of silybin in pre- and/or cancerogenic cells and anti-angiogenic activity of silybin are other important findings that bring silymarin preparations closer to respective application in the cancer treatment. Discovery of the inhibition and modulation of drug transporters, P-glycoproteins, estrogenic receptors, nuclear receptors by silybin and some of its new derivatives contribute further to the better understanding of silybin activity on the molecular level. Silymarin application in veterinary medicine is reviewed as well. Recent works using optically pure silybin diastereomers clearly indicate extreme importance of the use of optically active silybin namely in the receptor studies. Significance of silymarin and its components in the medicine is clearly indicated by an exponential growth of publications on this topic--over 800 papers in the last 5 years.
PMID: 17305535 [PubMed - indexed for MEDLINE]
Milk Thistle and Prostate Cancer: Differential Effects of Pure Flavonolignans from Silybum marianum on Antiproliferative End Points in Human Prostate Carcinoma Cells
Milk Thistle and Prostate Cancer: Differential Effects of Pure Flavonolignans from Silybum marianum on Antiproliferative End Points in Human Prostate Carcinoma Cells
Paula R. Davis-Searles1, Yuka Nakanishi1, Nam-Cheol Kim1, Tyler N. Graf1, Nicholas H. Oberlies1, Mansukh C. Wani1, Monroe E. Wall1, Rajesh Agarwal2 and David J. Kroll1
1 Natural Products Laboratory, Research Triangle Institute, Research Triangle Park, North Carolina and 2 Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado
Abstract
Extracts from the seeds of milk thistle, Silybum marianum, are known commonly as silibinin and silymarin and possess anticancer actions on human prostate carcinoma in vitro and in vivo. Seven distinct flavonolignan compounds and a flavonoid have been isolated from commercial silymarin extracts. Most notably, two pairs of diastereomers, silybin A and silybin B and isosilybin A and isosilybin B, are among these compounds. In contrast, silibinin is composed only of a 1:1 mixture of silybin A and silybin B. With these isomers now isolated in quantities sufficient for biological studies, each pure compound was assessed for antiproliferative activities against LNCaP, DU145, and PC3 human prostate carcinoma cell lines. Isosilybin B was the most consistently potent suppressor of cell growth relative to either the other pure constituents or the commercial extracts. Isosilybin A and isosilybin B were also the most effective suppressors of prostate-specific antigen secretion by androgen-dependent LNCaP cells. Silymarin and silibinin were shown for the first time to suppress the activity of the DNA topoisomerase II
gene promoter in DU145 cells and, among the pure compounds, isosilybin B was again the most effective. These findings are significant in that isosilybin B composes no more than 5% of silymarin and is absent from silibinin. Whereas several other more abundant flavonolignans do ultimately influence the same end points at higher exposure concentrations, these findings are suggestive that extracts enriched for isosilybin B, or isosilybin B alone, might possess improved potency in prostate cancer prevention and treatment.
http://cancerres.aacrjournals.org/cgi/content/full/65/10/4448
Anticancer potential of silymarin: from bench to bed side
1: Anticancer Res. 2006 Nov-Dec;26(6B):4457-98.
Anticancer potential of silymarin: from bench to bed side.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Silymarin consists of a family of flavonoids (silybin, isosilybin, silychristin, silydianin and taxifoline) commonly found in the dried fruit of the milk thistle plant Silybum marianum. Although silymarin's role as an antioxidant and hepatoprotective agent is well known, its role as an anticancer agent has begun to emerge. Extensive research within the last decade has shown that silymarin can suppress the proliferation of a variety of tumor cells (e.g., prostate, breast, ovary, colon, lung, bladder); this is accomplished through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors (such as p15, p21 and p27), down-regulation of anti-apoptotic gene products (e.g., Bcl-2 and Bcl-xL), inhibition of cell-survival kinases (AKT, PKC and MAPK) and inhibition of inflammatory transcription factors (e.g., NF-kappaB). Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (cyclin D1, EGFR, COX-2, TGF-beta, IGF-IR), invasion (MMP-9), angiogenesis (VEGF) and metastasis (adhesion molecules). The antiinflammatory effects of silymarin are mediated through suppression of NF-kappaB-regulated gene products, including COX-2, LOX, inducible iNOS, TNF and IL-1. Numerous studies have indicated that silymarin is a chemopreventive agent in vivo against a variety of carcinogens/tumor promoters, including UV light, 7,12-dimethylbenz(a)anthracene (DMBA), phorbol 12-myristate 13-acetate (PMA) and others. Silymarin has also been shown to sensitize tumors to chemotherapeutic agents through down-regulation of the MDR protein and other mechanisms. It binds to both estrogen and androgen receptors, and down-regulates PSA. In addition to its chemopreventive effects, silymarin exhibits antitumor activity against human tumors (e.g., prostate and ovary) in rodents. Various clinical trials have indicated that silymarin is bioavailable and pharmacologically safe. Studies are now in progress to demonstrate the clinical efficacy of silymarin against various cancers.
PMID: 17201169 [PubMed - indexed for MEDLINE]
Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine
1: Indian J Med Res. 2006 Nov;124(5):491-504.
Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine.
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research, Pondicherry, India. scpradhan@jipmer.edu
Silymarin, a flavonolignan from 'milk thistle' (Silybum marianum) plant is used almost exclusively for hepatoprotection and amounts to 180 million US dollars business in Germany alone. In this review we discuss about its safety, efficacy and future uses in liver diseases. The use of silymarin may replace the polyherbal formulations and will avoid the major problems of standardization, quality control and contamination with heavy metals or bacterial toxins. Silymarin consists of four flavonolignan isomers namely--silybin, isosilybin, silydianin and silychristin. Among them, silybin being the most active and commonly used. Silymarin is orally absorbed and is excreted mainly through bile as sulphates and conjugates. Silymarin offers good protection in various toxic models of experimental liver diseases in laboratory animals. It acts by antioxidative, anti-lipid peroxidative, antifibrotic, anti-inflammatory, membrane stabilizing, immunomodulatory and liver regenerating mechanisms. Silymarin has clinical applications in alcoholic liver diseases, liver cirrhosis, Amanita mushroom poisoning, viral hepatitis, toxic and drug induced liver diseases and in diabetic patients. Though silymarin does not have antiviral properties against hepatitis virus, it promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation and protects against glutathione depletion. Silymarin may prove to be a useful drug for hepatoprotection in hepatobiliary diseases and in hepatotoxicity due to drugs. The non traditional use of silymarin may make a breakthrough as a new approach to protect other organs in addition to liver. As it is having a good safety profile, better patient tolerability and an effective drug at an affordable price, in near future new derivatives or new combinations of this drug may prove to be useful.
PMID: 17213517 [PubMed - indexed for MEDLINE]
Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver
1: Indian J Biochem Biophys. 2006 Oct;43(5):306-11.
Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver.
Department of Biochemistry, Amrita Institute of Medical Sciences, Cochin 682 026, Kerala, India. subirkumardas@aims.amrita.edu
The production of reactive oxygen species (ROS) is considered to be a major factor in oxidative cell injury. The antioxidant activity or the inhibition of the generation of free radicals is important in providing protection against such hepatic damage. Silymarin, derived from the milk thistle plant, Silybium marianum, has been used in traditional medicine as a remedy for diseases of the liver and biliary tract. In the present study, the effect of hepatoprotective drug silymarin on body weight and biochemical parameters, particularly, antioxidant status of ethanol-exposed rats was studied and its efficacy was compared with the potent antioxidant, ascorbic acid as well as capacity of hepatic regeneration during abstention. Ethanol, at a dose of 1.6 g/kg body wt/day for 4 wks affected body weight in 16-18 week-old male albino rats (Wistar strain weighing 200-220 g). Thiobarbituric acid reactive substance (TBARS) level, superoxide dismutase (SOD), and glutathione-s-transferase (GST) activities were significantly increased, whereas GSH content, and catalase, glutathione reductase (GR) and GPx (glutathione peroxidase) activities significantly reduced, on ethanol exposure. These changes were reversed by silybin and ascorbic acid treatment. It was also observed that abstinence from ethanol might help in hepatic regeneration. Silybin showed a significant hepatoprotective activity, but activity was less than that of ascorbic acid. Furthermore, preventive measures were more effective than curative treatment.
PMID: 17133738 [PubMed - indexed for MEDLINE]
