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The Official Milk Thistle / Silymarin Thread


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#1 VespeneGas

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Posted 26 February 2010 - 09:11 AM


As a mechanism to distract myself from my studies, I did a little digging into our heretofore lightly discussed friend, milk thistle (active constituent blend: silymarin, most studied single constituent: silibinin). WOW. There's been an explosion of research on this herb over the past decade.

It seems to protect against just about any toxin you can think of, partly by upregulating endogenous antioxidant production (but it also appears to stimulate protein synthesis and repair in the liver and kidneys, slow the rate at which toxins enter liver cells... etc etc). Additionally, it appears to decrease LDL, oxLDL, trigylcerides, fasting glucose, hemoglobin glycation, and inflammation, and may reduce cancer risk. It appears to be exceptionally safe, with GI complaints and rashes being the primary ADR's, and appears to have few drug interactions. And it activates SIRT1, if you're into that sort of thing!

I am very excited to follow this suite of compounds over the next few years. I'm sure it has its limitations and risks, sorry for the rather uncharacteristic enthusiasm. Also, sorry for the wall-o-studies, I just thought I might compile some resources for common perusal and discussion.

GENERAL

An Updated Systematic Review of the Pharmacology of Silymarin

R. Sallera; J. Melzera; J. Reichlingb; R. Brignolic; R. Meierd
Recent years have seen an explosion of scientific papers that deal with drugs from the fruits of milk thistle and its active substances silymarin (standardized mixture of flavonolignanes), thus justifying an updated systematic review. Methods: Electronic databases identified silymarin, silibinin, silicristin or milk thistle as descriptors in >700 papers (34% published in last 5 years; 92% dealt with animal pharmacological). Only papers adequately reporting on experimental conditions, dosing, variables tested and statistics were analysed. Results: Silymarin was found to modify specifically the functions related to various transporters and receptors located in the cell membranes; that is, organic anion uptake transporter peptides (OATP), ABC transporters (P-gp), bile salt export pump, as well as TNF-a-dependent and possibly selectin-dependent phenomena. In the cytoplasm, some antioxidant properties and the inhibition of the lipoxygenase pathway seem quite selective and could concur to the antitoxic effects. Some effects like the inhibition of inducible nitric-oxide synthase, of nuclear factor B, and reduction of collagen synthesis are indicative of DNA/RNAmediated effects. Several studies using ‘in vitro’ and ‘in vivo’ cancer models suggest a potential of silymarin in such diseases. Topical and systemic silymarin has skin protective properties against UV-induced damage in epidermis and causes an up-regulation of tumour-suppressor genes p53- and p21CIP1. There were no data on hepatic viral replication, viremia or spontaneous tumours in the data examined. Conclusions: Data presented here do not solve the question about the complex mechanism(s) of action of the medicinal herbal drug silymarin. Silymarin may be a natural multi-functional and multi-target drug.
Copyright © 2007 S. Karger GmbH, Freiburg

Integr Cancer Ther. 2007 Jun;6(2):146-57.
Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.).
Tamayo C, Diamond S.
Research and Development at Flora Inc, Bethesda, MD 20817, USA. ctamayo2@comcast.net
Milk thistle extracts have been used as traditional herbal remedies for almost 2000 years. The extracts are still widely used to protect the liver against toxins and to control chronic liver diseases. Recent experimental and clinical studies suggest that milk thistle extracts also have anticancer, antidiabetic, and cardioprotective effects. This article reviews clinical trials of milk thistle conducted in the past 5 years including pharmacokinetic and toxicity studies, herb-drug interactions, and other safety issues. Several trials have studied the effects of milk thistle for patients with liver diseases, cancer, hepatitis C, HIV, diabetes, and hypercholesterolemia. Promising results have been reported in the protective effect of milk thistle in certain types of cancer, and ongoing trials will provide more evidence about this effect. In addition, new established doses and improvement on the quality and standardization of this herb will provide the much-awaited evidence about the efficacy of milk thistle in the treatment of liver diseases. Milk thistle extracts are known to be safe and well tolerated, and toxic or adverse effects observed in the reviewed clinical trials seem to be minimal. The future of milk thistle research is promising, and high-quality randomized clinical trials on milk thistle versus placebo may be needed to further demonstrate the safety and efficacy of this herb.
PMID: 17548793 [PubMed - indexed for MEDLINE]

Integr Cancer Ther. 2007 Jun;6(2):104-9.
Advances in the use of milk thistle (Silybum marianum).
Post-White J, Ladas EJ, Kelly KM.
University of Minnesota, Minneapolis, Minnesota 55403, USA. postw001@umn.edu

Milk thistle (Silybum marianum) is an herbal supplement used to treat liver and biliary disorders. Silymarin, a mixture of flavanoid complexes, is the active component that protects liver and kidney cells from toxic effects of drugs, including chemotherapy. Although milk thistle has not significantly altered the course of chronic liver disease, it has reduced liver enzyme levels and demonstrated anti-inflammatory and T cell-modulating effects. There is strong preclinical evidence for silymarin's hepatoprotective and anticarcinogenic effects, including inhibition of cancer cell growth in human prostate, skin, breast, and cervical cells. Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. More clinical trials of rigorous methodology, using standardized and well-defined products and dosages, are needed to evaluate the potential of silymarin against liver toxicity, chronic liver disease, and human cancers.
PMID: 17548789 [PubMed - indexed for MEDLINE]

LIVER

Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver
SUBIR KUMAR DAS ; VASUDEVAN D. M. ;

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 (TEARS) 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.

Indian journal of biochemistry & biophysics
J Clin Gastroenterol. 2003 Oct;37(4):336-9.
Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons.
Lieber CS, Leo MA, Cao Q, Ren C, DeCarli LM.
Section of Liver Disease & Nutrition, Bronx VA Medical Center & Mount Sinai School of Medicine, Bronx, New York 10468, USA. liebercs@aol.com
GOAL/BACKGROUND: Hepatoprotective effects of silymarin in patients with alcoholic liver disease are controversial. For strict control, this was assessed in non-human primates. STUDY Twelve baboons were fed alcohol with or without silymarin for 3 years with a nutritionally adequate diet. RESULTS: Silymarin opposed the alcohol-induced oxidative stress (assessed by plasma 4-hydroxynonenal) and the rise in liver lipids and circulating ALT. Alcohol also increased hepatic collagen type I by 50% over the 3 years with a significant rise in mRNA for alpha1 (I) procollagen, both prevented by silymarin. There were corresponding morphologic changes: at 36 months, 2 of 6 animals fed alcohol had cirrhosis and 2 septal fibrosis, with perivenular fibrosis in 2, whereas with alcohol + silymarin, there was only 1 cirrhosis and 1 septal fibrosis, with perivenular fibrosis in 2, and virtually no lesions in the remaining 2. CONCLUSIONS: Silymarin retards the development of alcohol-induced hepatic fibrosis in baboons, consistent with several positive clinical trials. The negative outcome observed in other trials possibly reflects poor compliance resulting in irregular or low silymarin intake. Thus, in view of the innocuity of silymarin, it might be advisable in future clinical studies to insure the controlled administration of sufficient amounts of silymarin.
PMID: 14506392 [PubMed - indexed for MEDLINE]

Nutr Metab (Lond). 2008 Jul 5;5:18.
Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals.
Eminzade S, Uraz F, Izzettin FV.
Department of Pharmacology, Marmara University, Faculty of Pharmacy, Haydarpasa, Istanbul, Turkey. seminzade@hotmail.com.
ABSTRACT: BACKGROUND: The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs. METHODS: Male Wistar albino rats weighing 250-300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg) and rifampicin (100 mg/kg); and intra-gastric administration of pyrazinamid (350 mg/kg) and silymarin (200 mg/kg). Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin. RESULTS: Treatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs. CONCLUSION: The active components of silymarin had protective effects against hepatotoxic actions of drugs used in the chemotherapy of tuberculosis in animal models. Since no significant toxicity of silymarin is reported in human studies, this plant extract can be used as a dietary supplement by patients taking anti-tuberculosis medications.
PMID: 18601745 [PubMed - in process]

Indian J Med Res. 2006 Nov;124(5):491-504.
Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine.
Pradhan SC, Girish C.
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]

Drugs. 2001;61(14):2035-63.
The use of silymarin in the treatment of liver diseases.
Saller R, Meier R, Brignoli R.
Abteilung Naturheilkunde, University Hospital Zurich, Switzerland.
The high prevalence of liver diseases such as chronic hepatitis and cirrhosis underscores the need for efficient and cost-effective treatments. The potential benefit of silymarin (extracted from the seeds of Silybum marianum or milk thistle) in the treatment of liver diseases remains a controversial issue. Therefore, the objective of this review is to assess the clinical efficacy and safety of silymarin by application of systematic approach. 525 references were found in the databases, of which 84 papers were retained for closer examination and 36 were deemed suitable for detailed analysis. Silymarin has metabolic and cell-regulating effects at concentrations found in clinical conditions, namely carrier-mediated regulation of cell membrane permeability, inhibition of the 5-lipoxygenase pathway, scavenging of reactive oxygen species (ROS) of the R-OH type and action on DNA-expression, for example, via suppression of nuclear factor (NF)-kappaB. Pooled data from case record studies involving 452 patients with Amanita phalloides poisoning show a highly significant difference in mortality in favour of silibinin [the main isomer contained in silymarin] (mortality 9.8% vs 18.3% with standard treatment; p < 0.01). The available trials in patients with toxic (e.g. solvents) or iatrogenic (e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered, do not enable any valid conclusions to be drawn on the value of silymarin. The exception is an improved clinical tolerance of tacrine. In spite of some positive results in patients with acute viral hepatitis, no formally valid conclusion can be drawn regarding the value of silymarin in the treatment of these infections. Although there were no clinical end-points in the four trials considered in patients with alcoholic liver disease, histological findings were reported as improved in two out of two trials, improvement of prothrombin time was significant (two trials pooled) and liver transaminase levels were consistently lower in the silymarin-treated groups. Therefore, silymarin may be of use as an adjuvant in the therapy of alcoholic liver disease. Analysis was performed on five trials with a total of 602 patients with liver cirrhosis. The evidence shows that, compared with placebo, silymarin produces a nonsignificant reduction of total mortality by -4.2% [odds ratio (OR) 0.75 (0.5 - 1.1)]; but that, on the other hand, the use of silymarin leads to a significant reduction in liver-related mortality of-7% [OR: 0.54 (0.3 - 0.9); p < 0.01]. An individual trial reported a reduction in the number of patients with encephalopathy of -8.7% (p = 0.06). In one study of patients with cirrhosis-related diabetes mellitus, the insulin requirement was reduced by -25% (p < 0.01). We conclude that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis. Silymarin is has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. This review does not aim to replace future prospective trials aiming to provide the 'final' evidence of the efficacy of silymarin.
PMID: 11735632 [PubMed - indexed for MEDLINE]

The list really goes on and on for the liver...


BRAIN

Food Chem Toxicol. 2009 Oct;47(10):2655-60. Epub 2009 Aug 6.
Effect of silymarin on biochemical parameters of oxidative stress in aged and young rat brain.
Galhardi F, Mesquita K, Monserrat JM, Barros DM.
Instituto de Ciências Biológicas, Universidade Federal do Rio GrandeRio Grande, RS, Brazil.
Silymarin (SM), the active complex of milk thistle, is a lipophilic fruit extract and is composed of several isomer flavonolignans. Flavonoids are antioxidants found molecules capable of intercepting reactive oxygen species (ROS). The oxidative stress (OS) is caused by imbalance between antioxidant defenses and production of ROS causing oxidative damage to macromolecules. Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. This study evaluated the effect of SM on biochemical parameters that evaluate OS in aged and young rat brain. For measures of OS were used measures of total oxyradical scavenging capacity (ACAP) through the concentration of ROS by fluorescence, lipid peroxidation (LPO), via FOX and TBARS, proteins oxidation by Western blot (WB). Rats were treated with SM at doses of 200 and 400mg/kg/day (SM200 and SM400). The LPO analyzed through FOX was increased in the hippocampus of aged animals treated with SM400, but in the cortex of young and aged, the highest dose of SM decreased LPO analyzed through TBARS. Both doses have seemed most effective in the reduction of oxidized proteins in aged brain. These results suggest that SM may contribute to the prevention of aged-related and pathological degenerative processes in the brain.
PMID: 19647779 [PubMed - indexed for MEDLINE]

Br J Pharmacol. 2009 Aug;157(7):1270-7. Epub 2009 Jun 22.
Silibinin prevents amyloid beta peptide-induced memory impairment and oxidative stress in mice.
Lu P, Mamiya T, Lu LL, Mouri A, Zou L, Nagai T, Hiramatsu M, Ikejima T, Nabeshima T.
Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Japan.
BACKGROUND AND PURPOSE: Accumulated evidence suggests that oxidative stress is involved in amyloid beta (Abeta)-induced cognitive dysfunction. Silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), has been shown to have antioxidative properties; however, it remains unclear whether silibinin improves Abeta-induced neurotoxicity. In the present study, we examined the effect of silibinin on the memory impairment and accumulation of oxidative stress induced by Abeta(25-35) in mice. EXPERIMENTAL APPROACH: Aggregated Abeta(25-35) (3 nmol) was intracerebroventricularly administered to mice. Treatment with silibinin (2, 20 and 200 mg.kg(-1), once a day, p.o.) was started immediately after the injection of Abeta(25-35). Locomotor activity was evaluated 6 days after the Abeta(25-35) treatment, and cognitive function was evaluated in a Y-maze and novel object recognition tests 6-11 days after the Abeta(25-35) treatment. The levels of lipid peroxidation (malondialdehyde) and antioxidant (glutathione) in the hippocampus were measured 7 days after the Abeta(25-35) injection. KEY RESULTS: Silibinin prevented the memory impairment induced by Abeta(25-35) in the Y-maze and novel object recognition tests. Repeated treatment with silibinin attenuated the Abeta(25-35)-induced accumulation of malondialdehyde and depletion of glutathione in the hippocampus. CONCLUSIONS AND IMPLICATIONS: Silibinin prevents memory impairment and oxidative damage induced by Abeta(25-35) and may be a potential therapeutic agent for Alzheimer's disease.
PMID: 19552690 [PubMed - indexed for MEDLINE]

J Pharmacol Exp Ther. 2009 Oct;331(1):319-26. Epub 2009 Jul 28.
Silibinin attenuates amyloid beta(25-35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice.
Lu P, Mamiya T, Lu LL, Mouri A, Niwa M, Hiramatsu M, Zou LB, Nagai T, Ikejima T, Nabeshima T.
Department of Chemical Pharmacology, Meijo University, Nagoya, Japan.
In Alzheimer's disease (AD), the deposition of amyloid peptides is invariably associated with oxidative stress and inflammatory responses. Silibinin (silybin), a flavonoid derived from the herb milk thistle, has potent anti-inflammatory and antioxidant activities. However, it remains unclear whether silibinin improves amyloid beta (Abeta) peptide-induced neurotoxicity. In this study, we examined the effect of silibinin on the fear-conditioning memory deficits, inflammatory response, and oxidative stress induced by the intracerebroventricular injection of Abeta peptide(25-35) (Abeta(25-35)) in mice. Mice were treated with silibinin (2, 20, and 200 mg/kg p.o., once a day for 8 days) from the day of the Abeta(25-35) injection (day 0). Memory function was evaluated in cued and contextual fear-conditioning tests (day 6). Nitrotyrosine levels in the hippocampus and amygdala were examined (day 8). The mRNA expression of inducible nitric-oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in the hippocampus and amygdala was measured 2 h after the Abeta(25-35) injection. We found that silibinin significantly attenuated memory deficits caused by Abeta(25-35) in the cued and contextual fear-conditioning test. Silibinin significantly inhibited the increase in nitrotyrosine levels in the hippocampus and amygdala induced by Abeta(25-35). Nitrotyrosine levels in these regions were negatively correlated with memory performance. Moreover, real-time RT-PCR revealed that silibinin inhibited the overexpression of iNOS and TNF-alpha mRNA in the hippocampus and amygdala induced by Abeta(25-35). These findings suggest that silibinin (i) attenuates memory impairment through amelioration of oxidative stress and inflammatory response induced by Abeta(25-35) and (ii) may be a potential candidate for an AD medication.
PMID: 19638571 [PubMed - indexed for MEDLINE]

Bull Exp Biol Med. 2007 Dec;144(6):806-9.
Effect of silimarin, succinic acid, and their combination on bioenergetics of the brain in experimental encephalopathy.
Khazanov VA, Vengerovsky AI.
Laboratory of Molecular Pharmacology, Institute of Pharmacology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences.
In rats with experimental encephalopathy caused by intoxication with 4-pentenoic acid inhibiting beta-oxidation of medium- and long-chain fatty acids, hepatoprotector silimarin inhibited LPO, prevented deenergization and maintained high respiratory activity of brain mitochondria, and increased the rate and coupling of oxidation and phosphorylation. Succinic acid improved oxidation of substrates in motochondria and promoted activation of succinate-dependent ATP generation. Silimarin and succinic acid used together produced a synergistic protective effect on brain mitochondria surpassing the protective effects of individual preparations and prevented LPO activation.
PMID: 18856206 [PubMed - indexed for MEDLINE]

J Surg Res. 2008 Apr;145(2):214-22. Epub 2007 Oct 22.
Silymarin, the antioxidant component of Silybum marianum, prevents sepsis-induced acute lung and brain injury.
Toklu HZ, Tunali Akbay T, Velioglu-Ogunc A, Ercan F, Gedik N, Keyer-Uysal M, Sener G.
Department of Pharmacology, School of Pharmacy, Marmara University, Istanbul, Turkey.
BACKGROUND: Sepsis is associated with enhanced generation of reactive oxygen species, which leads to multiple organ dysfunctions. Based on the potent antioxidant effects of silymarin, we investigated the putative protective role of silymarin against sepsis-induced oxidative damage in lung and brain tissues. MATERIALS AND METHODS: Sepsis was induced by cecal ligation and perforation (CLP). Sham and CLP groups received either vehicle or silymarin (50 mg/kg, p.o.) or 150 mg/kg i.p. N-acetylcysteine (NAC) for 10 days prior and immediately after the operation. Six hours after the surgery, rats were decapitated and blood was collected for the measurement of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta [IL-1 beta], and IL-6) levels, lactate dehydrogenase activity, and total antioxidant capacity. Lung and brain samples were taken for the measurement of malondialdehyde and glutathione levels, myeloperoxidase activity, thromboplastic activity, and also for histological assessment. Formation of reactive oxygen species in tissue samples was monitored by using chemiluminescence technique with luminol and lusigenin probe. RESULTS: Sepsis increased serum TNF-alpha, IL-1 beta, IL-6 levels, and lactate dehydrogenase activity and decreased total antioxidant capacity. On the other hand, tissue glutathione levels were decreased while malondialdehyde levels and myeloperoxidase activity were increased in both the lung and the brain tissues due to CLP. Furthermore, luminol and lucigenin chemiluminescence were significantly increased in the CLP group, indicating the presence of the oxidative damage. Silymarine and NAC treatment reversed these biochemical parameters and preserved tissue morphology as evidenced by histological evaluation. CONCLUSIONS: Silymarin, like NAC, reduced sepsis-induced remote organ injury, at least in part, through its ability to balance oxidant-antioxidant status, to inhibit neutrophil infiltration, and to regulate the release of inflammatory mediators.
PMID: 17950327 [PubMed - indexed for MEDLINE]

CANCER

Antioxid Redox Signal. 2002 Aug;4(4):655-63.
Flavonoid antioxidant silymarin and skin cancer.
Singh RP, Agarwal R.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Oxidative stress is one of the key players in skin carcinogenesis, and therefore identifying nontoxic strong antioxidants to prevent skin cancer is an important area of research. In both animal and cell culture studies, we have shown that silymarin, a naturally occurring polyphenolic flavonoid antioxidant, exhibits preventive and anticancer effects against skin cancer. For example, silymarin strongly prevents both photocarcinogenesis and skin tumor promotion in mice, in part, by scavenging free radicals and reactive oxygen species and strengthening the antioxidant system. We also found that this effect of silymarin is by inhibiting endogenous tumor promoter tumor necrosis factor alpha in mouse skin, a central mediator in skin tumor promotion. In mechanistic studies, silymarin inhibits mitogenic and cell survival signaling and induces apoptosis. Furthermore, silymarin effectively modulates cell-cycle regulators and check points toward inhibition of proliferation, and growth arrest in G0-G1 and G2-M phases of the cell cycle. Thus, due to its mechanism-based chemopreventive and anticancer effects in experimental models, silymarin is an important candidate for the prevention and/or therapy of skin cancer, as well as other cancers of epithelial origin in humans.
PMID: 12230878 [PubMed - indexed for MEDLINE]

Integr Cancer Ther. 2007 Jun;6(2):130-45.
Chemopreventive efficacy of silymarin in skin and prostate cancer.
Deep G, Agarwal R.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, CO 80262, USA.
Prevention and therapeutic intervention by phytochemicals are newer dimensions in the arena of cancer management. In this regard, the cancer chemopreventive role of silymarin (Silybum marianum) has been extensively studied and has shown anticancer efficacy against various cancer sites, especially skin and prostate. In skin cancer, silymarin treatment inhibits ultraviolet B radiation or chemically initiated or promoted carcinogenesis. These effects of silymarin against skin carcinogenesis have been attributed to its strong antioxidant and anti-inflammatory action as well as its inhibitory effect on mitogenic signaling. Similarly, silymarin treatment inhibits 3, 2-dimethyl-4-aminobiphenyl-induced prostate carcinogenesis and retards the growth of advanced prostate tumor xenograft in athymic nude mice. In prostate cancer, silymarin treatment down-regulates androgen receptor-, epidermal growth factor receptor-, and nuclear factor-kappaB- mediated signaling and induces cell cycle arrest. Extensive preclinical findings have supported the anticancer potential of silymarin, and now its efficacy is being evaluated in cancer patients.
PMID: 17548792 [PubMed - indexed for MEDLINE]

Int J Oncol. 2005 Jan;26(1):169-76.
Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects (Review).
Katiyar SK.
Department of Dermatology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA. skatiyar@uab.edu
Several environmental and genetic factors are involved in skin cancer induction, however exposure to chemical carcinogens and solar ultraviolet (UV) radiation are primarily responsible for several skin diseases including skin cancer. Chronic exposure of solar UV radiation to the skin leads to basal cell and squamous cell carcinoma, and melanoma. Chemoprevention of skin cancer by consumption of naturally occurring botanicals appears a practical approach and therefore world-wide interest is considerably increasing to use these botanicals. Sunscreens are useful but their protection is not ideal because of inadequate use, incomplete spectral protection and toxicity. Silymarin, a plant flavonoid isolated from the seeds of milk thistle (Silybum marianum), has been shown to have chemopreventive effects against chemical carcinogenesis as well as photocarcinogenesis in various animal tumor models. Topical treatment of silymarin inhibited 7,12-dimethylbenz(a)anthracene-initiated and several tumor promoters, like 12-O-tetradecanoylphorbol-13-acetate, mezerein, benzoyal peroxide and okadaic acid, induced skin carcinogenesis in mouse models. Similarly, silymarin also prevented UVB-induced skin carcinogenesis. Wide range of in vivo mechanistic studies indicated that silymarin possesses antioxidant, anti-inflammatory and immunomodulatory properties which may lead to the prevention of skin cancer in in vivo animal models. The available experimental information suggests that silymarin is a promising chemopreventive and pharmacologically safe agent which can be exploited or tested against skin cancer in human system. Moreover, silymarin may favorably supplement sunscreen protection and provide additional anti-photocarcinogenic protection.
PMID: 15586237 [PubMed - indexed for MEDLINE]

Anticancer Agents Med Chem. 2009 Dec 16. [Epub ahead of print]
Silibinin - A Promising New Treatment for Cancer.
Cheung CW, Gibbons N, Johnson DW, Nicol DL.
Departments of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Brisbane, Queensland, Australia. catherine_cheung@health.qld.gov.au.
Silymarin and its major constituent, Silibinin, are extracts from the medicinal plant Silybum marianum (milk thistle) and have traditionally been used for the treatment of liver diseases. Recently, these orally active, flavonoid agents have also been shown to exert significant anti-neoplastic effects in a variety of in vitro and in vivo cancer models, including skin, breast, lung, colon, bladder, prostate and kidney carcinomas. The aim of the present review is to examine the pharmacokinetics, mechanisms, effectiveness and adverse effects of silibinin's anti-cancer actions reported to date in pre-clinical and clinical trials. The review will also discuss the results of current research efforts seeking to determine the extent to which the effectiveness of silibinin as an adjunct cancer treatment is influenced by such factors as histologic subtype, hormonal status, stromal interactions and drug metabolising gene polymorphisms. The results of these studies may help to more precisely target and dose silibinin therapy to optimise clinical outcomes for oncology patients.
PMID: 20015009 [PubMed - as supplied by publisher]

Cancer Lett. 2008 Oct 8;269(2):352-62. Epub 2008 May 9.
Multitargeted therapy of cancer by silymarin.
Ramasamy K, Agarwal R.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, 4200 East Ninth Street, Box C238, Denver, CO 80262, USA.
Silymarin, a flavonolignan from milk thistle (Silybum marianum) plant, is used for the protection against various liver conditions in both clinical settings and experimental models. In this review, we summarize the recent investigations and mechanistic studies regarding possible molecular targets of silymarin for cancer prevention. Number of studies has established the cancer chemopreventive role of silymarin in both in vivo and in vitro models. Silymarin modulates imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis. In addition, silymarin also showed anti-inflammatory as well as anti-metastatic activity. Further, the protective effects of silymarin and its major active constituent, silibinin, studied in various tissues, suggest a clinical application in cancer patients as an adjunct to established therapies, to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity. This review focuses on the chemistry and analogues of silymarin, multiple possible molecular mechanisms, in vitro as well as in vivo anti-cancer activities, and studies on human clinical trials.
[attachment=7694:nihms_72463_f0002.jpg]
Free author's manuscript, a good read.

BJU Int. 2007 Aug;100(2):438-44.
Therapeutic value of orally administered silibinin in renal cell carcinoma: manipulation of insulin-like growth factor binding protein-3 levels.
Cheung CW, Taylor PJ, Kirkpatrick CM, Vesey DA, Gobe GC, Winterford C, Nicol DL, Johnson DW.
Department of Medicine, University of Queensland, Brisbane, Queensland, Australia.
OBJECTIVES: To investigate if the feeding of silibinin (an anticancer flavonoid) to mice inhibits in vivo renal cell carcinoma (RCC) growth via changes in insulin-like growth factor binding protein-3 (IGFBP-3) levels. MATERIALS AND METHODS: Male severe combined immunodeficiency disease (SCID) mice (7 weeks old), with left kidneys injected with 1 million SN12K1 cells, were fed a silibinin-containing diet (0.1%, 0.2% and 0.4% w/w) or control AIN-93G diet for 39 days from 1 day after tumour engraftment. RESULTS: There was a reduction in tumour deposits and tumour kidney weight in SCID mice fed with a 0.4% silibinin-containing diet compared to those fed the control diet. Mice with tumour injection (silibinin or control-diet group) had constant total body weight and food consumption. The mean plasma and tumourous kidney silibinin concentrations, as measured by high-pressure liquid chromatography-tandem mass spectrometry, increased with escalating doses of silibinin. Using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, the mean tissue IGFBP-3 mRNA (in SN12K1-implanted kidney) and plasma IGFBP-3 levels increased in mice fed with 0.1% silibinin (tumour IGFBP-3 mRNA levels, 156% higher vs control-diet group, P = 0.007; and plasma IGFBP-3 levels, 61% higher vs control-diet group, P = 0.002) but not in mice fed with the higher silibinin pellet strengths. CONCLUSION: Oral administration of silibinin suppressed local and metastatic tumour growth in vivo in an orthotopic xenograft model of RCC. This anti-neoplastic action of silibinin might involve IGFBP-3. The exact mechanism through which IGFBP-3 promotes silibinin's anticancer effects warrants further investigation.
PMID: 17617146 [PubMed - indexed for MEDLINE]

DIABETES/LIPIDS

J Med Food. 2007 Sep;10(3):543-7.
Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes.
Hussain SA.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq. saad_alzaidi@yahoo.com
Oxidative stress is increased postprandially and during long-term hyperglycemia in type 2 diabetic patients who present with poor response to glibenclamide. This study was designed to evaluate the effects of the antioxidant flavonoid silymarin in improving long-term and postprandial glycemic and weight control in type 2 diabetic patients treated with glibenclamide. Using a randomized, double-blind, placebo-controlled design, 59 type 2 diabetic patients, previously maintained on 10 mg/day glibenclamide and diet control, with poor glycemic control, were randomized into three groups: the first two groups were treated with either 200 mg/day silymarin or placebo as adjuncts to glibenclamide, and the third group was maintained on glibenclamide alone for 120 days. Fasting and 4-hour postprandial plasma glucose, glycated hemoglobin (HbA(1c)), and body mass index (BMI) were evaluated at baseline and after 120 days. Compared with placebo, silymarin treatment significantly reduced both fasting and postprandial plasma glucose excursions, in addition to significantly reducing HbA(1c) levels and BMI after 120 days. No significantly different effects were observed for placebo compared to glibenclamide alone. In conclusion, adjunct use of silymarin with glibenclamide improves the glycemic control targeted by glibenclamide, during both fasting and postprandially, an effect that may be related to increased insulin sensitivity in peripheral tissues.
PMID: 17887949 [PubMed - indexed for MEDLINE]

Phytother Res. 2006 Dec;20(12):1036-9.
The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial.
Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M.
Department of Pharmacology, Institute of Medicinal Plants, ACECR Tehran, Iran. huseini_fallah@yahoo.com
Oxidative stresses are increasingly implicated in the pathogenesis of diabetic complications which may either cause direct pancreatic beta-cell damage or lead to metabolic abnormalities that can induce or aggravate diabetes. The valuable effect of antioxidant nutrients on the glycemic control of diabetic patients has been reported in experimental and clinical studies. The present study was designed to investigate the effects of the herbal medicine, Silybum marianum seed extract (silymarin), which is known to have antioxidant properties on the glycemic profile in diabetic patients. A 4-month randomized double-blind clinical trial was conducted in 51 type II diabetic patients in two well-matched groups. The first group (n = 25) received a silymarin (200 mg) tablet 3 times a day plus conventional therapy. The second group (n = 26) received the same therapy but a placebo tablet instead of silymarin. The patients were visited monthly and glycosylated hemoglobin (HbA(1)c), fasting blood glucose (FBS), insulin, total cholesterol, LDL and HDL, triglyceride, SGOT and SGPT levels were determined at the beginning and the end of the study. The results showed a significant decrease in HbA(1)c, FBS, total cholesterol, LDL, triglyceride SGOT and SGPT levels in silymarin treated patients compared with placebo as well as with values at the beginning of the study in each group. In conclusion, silymarin treatment in type II diabetic patients for 4 months has a beneficial effect on improving the glycemic profile.
PMID: 17072885 [PubMed - indexed for MEDLINE]

Diabetes Nutr Metab. 2002 Aug;15(4):222-31.
Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent.
Lirussi F, Beccarello A, Zanette G, De Monte A, Donadon V, Velussi M, Crepaldi G.
Department of Medical and Surgical Sciences, University of Padova, Italy. flavio.lirussi@unipd.it
BACKGROUND AND AIMS: In patients with non-insulin dependent diabetes mellitus (T2DM) and associated chronic liver disease, plasma levels of glucose, insulin and triglycerides are high, lipid peroxidation is increased and natural antioxidant reserves are reduced. Thus, we hypothesised that the re-balancing of cell redox levels and amelioration of liver function could result in a better glucose and lipid metabolism. To study this, we assessed the effect of a new oral formulation of an antioxidant agent - silybin-beta-cyclodextrin (named IBI/S) - in patients with chronic alcoholic liver disease and concomitant T2DM. METHODS: Sixty outpatients were enrolled in a three-centre, double blind, randomised, IBI/S vs placebo study. Forty-two (21 in the group IBI/S - 135 mg/d silybin per os - and 21 in the placebo group) concluded the 6-month treatment period. The efficacy parameters included fasting and mean daily plasma glucose levels, glycosylated hemoglobin (HbA1c), basal, stimulated C-peptide and insulin levels, total-, HDL-cholesterol and triglycerides levels in addition to conventional liver function tests. Insulin sensitivity was estimated by HOMA-IR. Malondialdehyde (MDA) was also measured before and after treatment as an index of oxidative stress. RESULTS: Fasting blood glucose levels, which were similar at baseline in IBI/S group and in the placebo group (173.9 mg/dl and 177.1 mg/dl, respectively), decreased to 148.4 mg/dl (-14.7% vs baseline; p = 0.03) in the IBI/S group while they were virtually unchanged in the placebo group. The comparison between the groups at mo 6 (T6) also showed a significant reduction of glucose levels in the IBI/S group (p = 0.03). The same trend was observed in mean daily blood glucose levels, HbA1c and HOMA-IR, although differences were not significant. Basal and stimulated C-peptide values showed that only a few changes had occured in both groups. Such results indicate that insulin secretion was virtually unaffected, as confirmed also by the insulinemia data. Plasma triglycerides concentrations dropped from a baseline value of 186 mg/dl to 111 mg/dl (T6) in the IBI/S group, with significant differences at all instances with respect to baseline values. By contrast, triglycerides increased from 159 mg/dl at entry to 185 mg/dl (T6) in the placebo group. The difference between the groups at T6 was highly significant (p < 0.01). Total and HDL cholesterol as well as liver function tests did not change significantly during the study in both groups. MDA decreased significantly only in the group receiving IBI/S. No clinically relevant side effects were observed in either group. CONCLUSIONS: Oral administration silybin-beta-cyclodextrin in patients with T2DM and compensated chronic alcoholic liver disease causes a significant decrease in both glucose and triglyceride plasma levels. These effects may be due to the recovery of energy substrates, consistent with a reduced lipid peroxidation and an improved insulin activity.
PMID: 12416659 [PubMed - indexed for MEDLINE]

J Hepatol. 1997 Apr;26(4):871-9.
Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients.
Velussi M, Cernigoi AM, De Monte A, Dapas F, Caffau C, Zilli M.
Anti-Diabetes Centre, Monfalcone Hospital, Gorizia, Italy.
BACKGROUND/AIMS: Several studies have demonstrated that diabetic patients with cirrhosis require insulin treatment because of insulin resistance. As chronic alcoholic liver damage is partly due to the lipoperoxidation of hepatic cell membranes, anti-oxidizing agents may be useful in treating or preventing damage due to free radicals. The aim of this study was to ascertain whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis. METHODS: A 12-month open, controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis. One group (n=30) received 600 mg silymarin per day plus standard therapy, while the control group (n=30) received standard therapy alone. The efficacy parameters, measured regularly during the study, included fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria levels, glycosylated hemoglobin (HbA1c) and malondialdehyde levels. RESULTS: There was a significant decrease (p<0.01) in fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria and HbA1c levels already after 4 months of treatment in the silymarin group. In addition, there was a significant decrease (p<0.01) in fasting insulin levels and mean exogenous insulin requirements in the treated group, while the untreated group showed a significant increase (p<0.05) in fasting insulin levels and a stabilized insulin need. These findings are consistent with the significant decrease (p<0.01) in basal and glucagon-stimulated C-peptide levels in the treated group and the significant increase in both parameters in the control group. Another interesting finding was the significant decrease (p<0.01) in malondialdehyde/levels observed in the treated group. CONCLUSIONS: These results show that treatment with silymarin may reduce the lipoperoxidation of cell membranes and insulin resistance, significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration.
PMID: 9126802 [PubMed - indexed for MEDLINE]

KIDNEYS

Invest New Drugs. 2009 Jul 10. [Epub ahead of print]

Dietary supplementation of silymarin protects against chemically induced nephrotoxicity, inflammation and renal tumor promotion response.
Kaur G, Athar M, Alam MS.

Department of Chemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062, India, gurpreet6@yahoo.com.

Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxicant and a renal carcinogen that induces its effect by causing oxidative stress. The present study was undertaken to explore protective effect of silymarin, a flavonolignan from milk thistle (Silybum marianum), against Fe-NTA mediated renal oxidative stress, inflammation and tumor promotion response along with elucidation of the implicated mechanism(s). Administration of Fe-NTA (10 mg/kg bd wt, i.p.) to Swiss albino mice induced marked oxidative stress in kidney, evident from augmentation in renal metallothionein (MT) expression, depletion of glutathione content and activities of antioxidant and phase II metabolizing enzymes, and enhancement in production of aldehyde products such as 4-hydroxy-2-nonenal. Fe-NTA also significantly activated nuclear factor kappa B (NFkappaB) and upregulated the expression of downstream genes: cyclooxygenase 2 and inducible nitric oxide synthase and enhancing the production of proinflammatory cytokines: tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). However, feeding of 0.5% and 1% silymarin diet conferred a significant protection against Fe-NTA induced oxidative stress and inflammation. It further augmented MT expression, restored the antioxidant armory, ameliorated NFkappaB activation and decreased the expression of proinflammatory mediators. Silymarin also suppressed Fe-NTA induced hyperproliferation in kidney, ameliorating renal ornithine decarboxylase activity and DNA synthesis. From these results, it could be concluded that silymarin markedly protects against chemically induced renal cancer and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.

PMID: 19590824 [PubMed - as supplied by publisher

Food Chem Toxicol. 2008 Jul;46(7):2422-8. Epub 2008 Apr 7.

Silymarin prevents adriamycin-induced cardiotoxicity and nephrotoxicity in rats.
El-Shitany NA, El-Haggar S, El-desoky K.

Department of Pharmacology and Toxicology, College of Pharmacy, Tanta University, Tanta, Egypt. Nagla_fouad@yahoo.com

Adriamycin is a potent anticancer agent, its clinical use is limited for its marked cardiotoxicity and nephrotoxicity. The present study aimed to investigate the possible protective role of the natural antioxidant silymarin on ADR-induced heart and kidney toxicity. Studies were performed on four groups of rats. 1--control group, 2--silymarin group (50 mg/kg), 3--adriamycin group (10 mg/kg), 4--adriamycin+silymarin group. On the third day after ADR injection, plasma was separated for determination of LDH, CPK, cholesterol and total lipids. 30 days after ADR injection, plasma was separated for determination of creatinine and urea levels. Frozen heart specimens (72 h) and frozen kidney specimens (30days) were used for estimation of lipid peroxides and GSH contents. Histopathological examinations of heart and kidney sections were also done. Pretreatment of ADR-treated rats with silymarin resulted in a significant decrease in the plasma CPK, LDH, creatinine and urea. On the other hand silymarin pretreatment did not change ADR-induced hyperlipidemia. Silymarin pretreatment significantly decreased the myocardial MDA contents. In addition, silymarin pretreatment normalized renal tissue contents of MDA and GSH. Histopathological examination of heart and kidney sections revealed that ADR caused only mild myocardial injury in silymarin pretreated rats. Also, silymarin pretreatment inhibited ADR-induced renal tubular damage in rats. These results have suggested that, silymarin ameliorated ADR-induced cardiotoxicity and protected against ADR-induced nephrotoxicity in male albino rats. The mechanisms of silymarin induced protection against ADR-induced toxicities were proved to be due to inhibition of lipid peroxidation and protection against GSH depletion.

PMID: 18487002 [PubMed - indexed for MEDLINE

World J Urol. 2008 Aug;26(4):401-7. Epub 2008 Apr 12.
Silymarin attenuates the renal ischemia/reperfusion injury-induced morphological changes in the rat kidney.
Senturk H, Kabay S, Bayramoglu G, Ozden H, Yaylak F, Yucel M, Olgun EG, Kutlu A.
Faculty of Science, Department of Biology, Osmangazi University, Eskisehir, Turkey. hsenturk@ogu.edu.tr
OBJECTIVES: Renal ischemia/reperfusion (I/R) injury is associated with increased mortality and morbidity rates due to acute renal failure (ARF). Oxidative stress induced with renal I/R injury directly affects glomerular and tubular epithelium through reactive oxygen species. Several studies have been directed to the treatment of renal I/R injury. The aim of this study was to test the attenuation with silymarin (SM) treatment of renal I/R injury-induced morphological changes in the rat kidney. METHODS: A total of 32 adult male Sprague-Dawley rats were evaluated in four groups. Group I (sham), Group II (renal I/R), Group III (renal I/R injury + SM 50 mg per kg) and Group IV (renal I/R injury + SM 100 mg per kg) were designed to evaluate the dose-dependent effects of SM on the morphological changes of renal I/R injury. Renal I/R injury were induced with left renal pedicle occlusion for 45 min followed with reperfusion for 6 h under anesthesia. After induction of I/R injury, left nephrectomies were performed for histopathological examinations. RESULTS: After renal I/R injury, significant tubular dilatation, tubular vacuolization, pelvic inflammation, interstitial inflammation, perirenal adipose infiltration, tubular necrosis and glomerular necrosis (cortical necrosis) were observed. However, even with low dose SM in Group III (50 mg per kg SM), histopathological changes due to I/R injury were prevented. CONCLUSIONS: The results of this study have demonstrated that SM significantly prevents renal I/R injury-induced renal tubular changes in the rat. SM in 50 mg/kg was observed to be sufficient to significantly prevent renal tubular necrosis. Further, to our literature knowledge, this is the first specific study to demonstrate the preventive effect of SM on renal I/R injury.
PMID: 18408933 [PubMed - indexed for MEDLINE]

ok, it's in vitro I know, but,

Stimulatory Effects of Silibinin and Silicristin from the Milk Thistle Silybum marianum on Kidney Cells
1. Johann Sonnenbichler1,
2. Fortunato Scalera1,
3. Isolde Sonnenbichler1 and
4. Roland Weyhenmeyer2
1. 1Max Planck Institute for Biochemistry, Martinsried, Germany (J.S., F.S., I.S.); and 2Madaus AG, Köln, Germany (R.W.)
The biochemical influence of flavonolignans from the milk thistleSilybum marianum has been tested on kidney cells of African green monkeys. Two nonmalignant cell lines were selected, with the focus of the work on the fibroblast-like Vero line. Proliferation rate, biosynthesis of protein and DNA, and the activity of the enzyme lactate dehydrogenase (as a measure of the cellular metabolic activity) were chosen as parameters for the effect of the flavonolignans. Silibinin and silicristin show remarkable stimulatory effects on these parameters, mainly in Vero cells; however, isosilibinin and silidianin proved to be inactive. In vitro experiments with kidney cells damaged by paracetamol, cisplatin, and vincristin demonstrated that administration of silibinin before or after the chemical-induced injury can lessen or avoid the nephrotoxic effects. The results warrant in vivo evaluations of the flavonolignan derivatives.

OTHER

Cellular and Molecular Life Sciences
Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity
J. v. Scho¨ nfelda,*, B. Weisbrodb and M. K. Mu¨ llerc

Silymarin can be extracted from the milk thistle, and silibinin is the main component of the plant extract. Possibly due to their antioxidant and membrane-stabilizing properties, the compounds have been shown to protect different organs and cells against a number of insults. Thus liver, kidney, erythrocytes and platelets have been protected from the toxic effects of ethanol, carbon tetrachloride, cold ischemia and drugs, respectively. The effect of silibinin on endocrine and exocrine pancreas, however, has not been studied. We therefore investigated whether silibinin treatment attenuates cyclosporin A (CiA) toxicity on rat endocrine and exocrine pancreas. Groups of 15 male Wistar rats were treated for 8 days with CiA and/or silibinin. On day 9, endocrine and exocrine pancreatic functions were tested in vitro. At the end of the treatment period, blood glucose levels in vivo were significantly higher in rats treated with CiA, while silibinin did not affect glucose levels. In vitro, insulin secretion was inhibited after treatment with silibinin, but amylase secretion was not affected. After treatment with CiA both insulin and amylase secretion were reduced. Silibinin and CiA had an additive inhibitory effect on insulin secretion, but silibinin attenuated CiA-induced inhibition of amylase secretion. Despite CiA treatment, amylase secretion was in fact restored to normal with the highest dose of silibinin. Thus silibinin inhibits glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo. This combination of effects could be useful in the treatment of non-insulin-dependent diabetes mellitus. Furthermore, silibinin protects the exocrine pancreas from CiA toxicity. As this inhibitory effect is probably unspecific, silibinin may also protect the exocrine pancreas against other insult principles, such as alcohol.
Free full text.

Toxicol In Vitro. 2008 Apr;22(3):610-7. Epub 2007 Dec 8.
Assessment of drug-drug interaction for silymarin.
Doehmer J, Tewes B, Klein KU, Gritzko K, Muschick H, Mengs U.
GenPharmTox Biotech AG, Fraunhofer Str. 9, D-82152 Planegg/Martinsried, Germany. johannes.doehmer@genpharmtox.de
Silymarin was assessed for drug-drug interaction by permeability studies with Caco-2 cells, for cytochrome P450 induction with human primary hepatocytes and for cytochrome P450 inhibition with human liver microsomes. Studies with Caco-2 cells revealed no interference of silymarin with the permeability of nifedipine. Silymarin did not induce cytochromes P450 2C9 and 3A4 at concentrations of 0.1; 1; and 100 microM, measured as silibinin. The inhibitory effect was tested on the nine major cytochromes P450 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 at concentrations of 1 and 100 microM silymarin. At 1 microM concentration no or negligible inhibition of cytochromes P450 1A2, 2A6, 2B6, 2C8, 2C9, and 2E1, minor inhibition of 3A4 (<20%), and moderate inhibition of 2C19 and 2D6 (<40%) were observed. Inhibition constant Ki of silymarin was determined for cytochromes P450 3A4 with 12 microM, 2C19 with 2 microM, and 2D6 with 12 microM. Only at the high concentration of 100 microM silymarin, inhibition at >50% of the cytochromes P450 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4 was observed, and no or moderate inhibition was for the cytochromes P450 1A2, 2A6, and 2E1. However, in view of the clinically relevant plasma concentration of approx. 0.2 microM measured as silibinin, it is evident that there is no drug-drug interaction problem with silymarin.
PMID: 18249085 [PubMed - indexed for MEDLINE]

Effects of Silymarin on the Acute Stage of the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Torcuata Cruz, Julio Gálvez*, Esperanza Crespo, M. Angeles Ocete, Antonio Zarzuelo
Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spai
Abstract
The intestinal anti-inflammatory activity of several doses of silymarin was tested in the acute stage of the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. The results obtained show that oral pre-treatment with 50 mg/kg of silymarin significantly attenuated macroscopic colonic damage as well as reduced colonic myeloperoxidase activity compared to non-treated colitic animals. The beneficial effect was accompanied by an improvement in the colonic oxidative status, which was altered in colonic inflammation, by preventing glutathione depletion and reducing malonyldialdehyde production. This suggests that the well known antioxidant properties of silymarin can participate in its intestinal anti-inflammatory activity. In addition, a preservation in the colonic absorptive function was also observed, and this effect can also account for the colonic protective effect observed in this model of acute colitis.

Central European Journal of Biology
On the benefits of silymarin in murine colitis by improving balance of destructive cytokines and reduction of toxic stress in the bowel cells
Hadi Esmaily1, Azadeh Hosseini-Tabatabaei1, Reza Rahimian1, Reza Khorasani1, Maryam Baeeri1, Ahmadreza Barazesh-Morgani1, Nargues Yasa2, Yassaman Khademi1 and Mohammad Abdollahi1

Abstract Inflammatory bowel disease (IBD) is a multifactorial disease with an unknown etiology characterized by oxidative stress, leucocyte infiltration and a rise in inflammatory cytokines. In this study, we have investigated the effects of silymarin, a mixture of several flavonolignans with established antioxidant and anti-inflammatory properties, on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Experimental colitis was induced in male Wistar-albino rats by delivering TNBS to the distal colon. All the medicines were administered by gavage for seven days. Thirty-six male rats were divided into six groups containing six rats in each one. Control rats received only TNBS. In the treated groups, animals were given different doses of silymarin (40, 80, and 160 mg/kg). Dexamethasone (1 mg/kg) was used as the positive treatment. Colonic status was investigated seven days post induction of colitis through macroscopic, histological, and biochemical analyses. Amelioration of the morphological signs including macroscopic damage, necrotic area, and histology were seen subsequent to treating animals with silymarin. These observations were accompanied by a significant reduction in the degree of both neutrophil infiltration, indicated by decreased myeloperoxidase activity, and lipid peroxidation, as measured by a decline in malodialdehyde content in inflamed colon as well as a decrease in levels of inflammatory cytokines (TNF-α and IL-1β). The results of the present study reveal that the beneficial effect of silymarin in bowel cells is mediated through its anti-oxidant and anti-inflammatory potentials.

Edited by VespeneGas, 26 February 2010 - 09:13 AM.

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#2 hamishm00

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Posted 26 February 2010 - 10:03 AM

Great thread.

LEF have a pretty good product, which is the one I go for. Each pill:

900 mg - Milk Thistle Extract (Silybum marianum) [std. to 80% Silymarin (720 mg), 30% Silibinin (270 mg), and 4.5% Isosilybin B (40.5 mg)]

I take between 2 and 4 per day (currently 2, at night). 750mg Resveratrol in the morning, 1800mgs Silymarin at night. I take Milk Thistle because I drink alcohol (in moderation), and because of the SIRT1 activation.

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#3 ppp

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Posted 26 February 2010 - 08:40 PM

As a mechanism to distract myself from my studies, I did a little digging into our heretofore lightly discussed friend, milk thistle (active constituent blend: silymarin, most studied single constituent: silibinin). WOW. There's been an explosion of research on this herb over the past decade.

It's also great for people on chemo struggling with hepatoxicity...

Edit: Trimmed quote.

Edited by niner, 26 February 2010 - 09:11 PM.


#4 FunkOdyssey

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Posted 26 February 2010 - 08:55 PM

Its not good for your health if it keeps you up all night posting about it. :-D Supplement research at 4:11am, lol Vespene. Nice work though.

#5 Hedrock

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Posted 26 February 2010 - 09:12 PM

What about Siliphos?

Is it better than normal silibinin?

#6 Clarity

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Posted 27 February 2010 - 10:19 PM

I love milk thistle and have used it for blood sugar control mostly with success. My only issue with it - and it's a big one - is that I find it can be disruptive to hormones. Namely, interfering with ovulation. I know there's not a lot of women on this board, but thought I'd mention it. I only take it 2 weeks out of the month, and wonder what it's doing even then. My feeling is that it can lower estrogen too much if used on a regular basis. Or maybe it's just me. :-D

#7 Declmem

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Posted 27 February 2010 - 10:25 PM

I asked this question a little while ago, but I'll re-pose it here:

Is there any benefit to taking milk thistle only when you are ingesting something that can be harmful to your liver - i.e. alcohol, modafinil, etc. ?

In other words, is long-term use the only way to achieve benefits, or could I just pop a couple pills on friday and saturday?

Edited by Declmem, 27 February 2010 - 10:26 PM.


#8 pycnogenol

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Posted 27 February 2010 - 11:42 PM

I take 2 capsules daily of milk thistle extract (Paradise Herbs brand, 75:1 potency).

Edited by pycnogenol, 27 February 2010 - 11:42 PM.


#9 rwac

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Posted 27 February 2010 - 11:55 PM

So what is the hormonal effect of silymarin, does anyone know ?

#10 nameless

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Posted 28 February 2010 - 12:23 AM

Any drug interaction concerns? From what I have glanced over from a couple of sites, it may not be the safest thing to take with certain drugs:

http://www.hcvadvoca...ts/mthistle.pdf

#11 VespeneGas

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Posted 28 February 2010 - 01:28 AM

Any drug interaction concerns? From what I have glanced over from a couple of sites, it may not be the safest thing to take with certain drugs:

http://www.hcvadvoca...ts/mthistle.pdf


Reposted from above:

Toxicol In Vitro. 2008 Apr;22(3):610-7. Epub 2007 Dec 8.
Assessment of drug-drug interaction for silymarin.
Doehmer J, Tewes B, Klein KU, Gritzko K, Muschick H, Mengs U.
GenPharmTox Biotech AG, Fraunhofer Str. 9, D-82152 Planegg/Martinsried, Germany. johannes.doehmer@genpharmtox.de
Silymarin was assessed for drug-drug interaction by permeability studies with Caco-2 cells, for cytochrome P450 induction with human primary hepatocytes and for cytochrome P450 inhibition with human liver microsomes. Studies with Caco-2 cells revealed no interference of silymarin with the permeability of nifedipine. Silymarin did not induce cytochromes P450 2C9 and 3A4 at concentrations of 0.1; 1; and 100 microM, measured as silibinin. The inhibitory effect was tested on the nine major cytochromes P450 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 at concentrations of 1 and 100 microM silymarin. At 1 microM concentration no or negligible inhibition of cytochromes P450 1A2, 2A6, 2B6, 2C8, 2C9, and 2E1, minor inhibition of 3A4 (<20%), and moderate inhibition of 2C19 and 2D6 (<40%) were observed. Inhibition constant Ki of silymarin was determined for cytochromes P450 3A4 with 12 microM, 2C19 with 2 microM, and 2D6 with 12 microM. Only at the high concentration of 100 microM silymarin, inhibition at >50% of the cytochromes P450 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4 was observed, and no or moderate inhibition was for the cytochromes P450 1A2, 2A6, and 2E1. However, in view of the clinically relevant plasma concentration of approx. 0.2 microM measured as silibinin, it is evident that there is no drug-drug interaction problem with silymarin.
PMID: 18249085 [PubMed - indexed for MEDLINE]

The warning you posted cites only this study, which used 100, 250, and 500 microM respectively. This is apparently at least 200 times more silymarin than gets into the bloodstream with typical use (0.2 microM silibinin).

Milk Thistle, a Herbal Supplement, Decreases the Activity of CYP3A4 and Uridine Diphosphoglucuronosyl Transferase in Human Hepatocyte Cultures Milk thistle extract is one of the most commonly used nontraditional therapies, particularly in Germany. Milk thistle is known to contain a number of flavonolignans. We evaluated the effect of silymarin, on the activity of various hepatic drug-metabolizing enzymes in human hepatocyte cultures. Treatment with silymarin (0.1 and 0.25 mM) significantly reduced the activity of CYP3A4 enzyme (by 50 and 100%, respectively) as determined by the formation of 6-β-hydroxy testosterone and the activity of uridine diphosphoglucuronosyl transferase (UGT1A6/9) (by 65 and 100%, respectively) as measured by the formation of 4-methylumbelliferone glucuronide. Silymarin (0.5 mM) also significantly decreased mitochondrial respiration as determined by MTT reduction in human hepatocytes. These observations point to the potential of silymarin to impair hepatic metabolism of certain coadministered drugs in humans. Indiscriminate use of herbal products may lead to altered pharmacokinetics of certain drugs and may result in increased toxicity of certain drugs.

@Funkodyssey: yeah, you're right, I was pretty exhausted during class the following day! Sleep dep |= longevity :-D

@Hedrock: siliphos is better absorbed and way more expensive than regular 80% silymarin standardized products.

@ Declmem: see "Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals" above, it does acutely protect against the toxicity of certain drugs and deathcap mushrooms. I can't say it does so for every toxin against which it protects (not having read the ~800 studies on the herb :-D ) but it seems likely.

@Pycnogenol: I wonder how much silymarin is in a gram of 75:1 potency milk thistle...
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#12 Declmem

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Posted 28 February 2010 - 08:56 PM

@ Declmem: see "Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals" above, it does acutely protect against the toxicity of certain drugs and deathcap mushrooms. I can't say it does so for every toxin against which it protects (not having read the ~800 studies on the herb :-D ) but it seems likely.


Thanks! So in at least some studies it was useful in the short-term to protect against toxicity. Was it take concurrently with the toxins in most studies you've looked at, then?


This looks like a good brand: http://www.iherb.com...Vcaps/4545?at=0

Not sure how it differs from the other Nature's Way milk thistle, which is also 80%. More standardized and absorb-able perhaps.

#13 TigerMask

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Posted 14 July 2010 - 12:24 AM

I was thinking about how people say it is unwise to take NAC shortly after drinking--even the day after--and that it should be taken before drinking. Is it beneficial or harmful to take Milk Thistle extract shortly after drinking (an hour or so)? And the next day?

#14 hamishm00

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Posted 14 July 2010 - 09:12 PM

What about at the same time?

What is the reasoning / consequences of not taking NAC before drinking, but afterwards?

#15 hippocampus

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Posted 08 September 2011 - 06:39 PM

OCD

Comparison of Silybum marianum (L.) Gaertn. with fluoxetine in the treatment of Obsessive−Compulsive Disorder

Mehdi Sayyah, Hatam Boostania, Siroos Paksereshta and Alireza Malayeria

Jundishapoor University of Medical Sciences, Ahwaz, Iran
Received 5 September 2009; revised 17 December 2009; accepted 17 December 2009. Available online 24 December 2009.
Abstract

Obsessive−Compulsive Disorder (OCD) is a common neuropsychiatric condition. Although a variety of pharmaceutical agents is available for the treatment of OCD, psychiatrists often find that many patients cannot tolerate the side effects of these medications; do not respond properly to the treatment; or the medications lose their effectiveness after a period of treatment. Herbal medicine can be a solution to some of these problems. In fact many herbs with psychotropic effects exist which can have fewer side effects. They can provide an alternative treatment or be used to enhance the effectiveness of conventional anti-obsessive and compulsive symptoms. Silybum marianum (L.) Gaertn. is a well-known medicinal plant with a long history of usage in Iran. This plant is reported to be safe on humans. Our objective in this study was to compare the efficacy of the extract of S. marianum (L.) with fluoxetine in the treatment of OCD. The study was an 8-week pilot double-blind randomized trial. Thirty five adult outpatients who met the DSM-IV-TR criteria for OCD based on the structured clinical interview participated in the trial. The minimum score of Yale–Brown Scale for OCD was 21 for all patients. In this double-blind and randomized trial, patients were randomly assigned to receive either capsule of the extract (600 mg/day) or fluoxetine (30 mg/day) for 8 weeks. The results showed no significant difference between the extract and fluoxetine in the treatment of OCD. There was also no significant difference between the two groups in terms of observed side effects.

Keywords: Obsessive–Compulsive Disorder; Silybum marianum; Yale–Brown Scale

Abbreviations: OCD, Obsessive–Compulsive Disorder; Y-BOCS, Yale–Brown Scale

gonna try this, I'll report in few weeks :)

#16 hippocampus

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Posted 08 September 2011 - 09:06 PM

this is getting even more interesting, it may be even nootropic (at least mild):

Alterations in Regional Brain Neurotransmitters by Silymarin, a Natural Antioxidant Flavonoid Mixture, in BALB/c Mice

Marcin Osuchowski, Victor Johnson, Quanren He and Raghubir Sharma

Silymarin, a natural antioxidant flavonoid mixture, exerts anti-inflammatory effects in the liver and hinders tumor formation. The effect of this flavonoid mixture on the central nervous system is unknown, although antioxidants are considered beneficial. Brain amines and metabolites were studied after a short-term silymarin treatment. BALB/c mice were intraperitoneally treated with 0, 10, 50, or 250 mg/kg of silymarin per day for 5 days. High-performance liquid chromatography coupled with electrochemical detection was performed to determine concentrations of norepinephrine (NE), dopamine (DA), dioxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT, serotonin) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete brain regions. Analyses showed increased 5-HT levels in the cortex and increased DA and NE levels in the cerebellum in the highest dose group. Results indicated lack of general adverse effect on the brain amine metabolism and suggest that silymarin may have marginal serotonergic, dopaminergic, and noradrenergic effects.

Neurotrophic and neuroprotective effects of milk thistle (Silybum marianum) on neurons in culture

Smita Kittur, Skuntala Wilasrusmee, Ward A. Pedersen, Mark. P. Mattson, Karen Straube-West, Chumpon Wilasrusmee, Burk Jubelt and Dilip S. Kittur
Abstract
Herbal products are being increasingly used as dietary supplements and therapeutic agents. However, much more research must be performed in order to determine the biological basis for their putative clinical effects. We tested the effects of milk thistle (Silybum marianum) extract on the differentiation and survival of cultured neural cells. Milk thistle enhanced nerve growth factor (NGF)-induced neurite outgrowth in PC-12 neural cells and prolonged their survival in culture. Milk thistle extract also protected cultured rat hippocampal neurons against oxidative stress-induced cell death. Our data demonstrate that milk thistle extract can promote neuronal differentiation and survival, suggesting potential benefits of chemicals in this plant on the nervous system.

#17 hippocampus

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Posted 09 September 2011 - 10:56 AM

from wikipedia: Silipide (trade name Siliphos), a complex of silymarin and phosphatidylcholine (lecithin), is about ten times more bioavailable than silymarin.[9]
http://en.wikipedia.org/wiki/Silymarin

does that mean it is better to take milk thistle with PC/lecithin?

#18 hippocampus

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Posted 11 September 2011 - 07:58 PM

THE EFFECT OF SILYMARIN ON LEARNING AND HISTOLOGICAL CHANGES OF HIPPOCAMPAL REGIONS OF RATS

YAGHMAEI PARICHEHR,PARIVAR KAZEM,DARAB M.*,ORYAN SHAHRBANOU,ABBASI ESMAEIL

* DEPARTMENT OF BIOLOGY, SCIENCE AND RESEARCH BRANCH, ISLAMIC AZAD UNIVERSITY, TEHRAN, IRAN



Background: Silymarin, an extract from seeds of milk thistle (Silybum marianum), is known to have hepato-protective, anticarcinogenic, antioxidant and estrogenic effects.
Objective: The aim of the present study was to test the effect of silymarin on passive avoidance learning in rats.
Methods: This was an experimental study carried on Wistar rats in Arak University, Iran. The animals were provided with silymarin (from day 7 of gestational age to 4 weeks after birth) at 2 doses of 180 mg/kg in the experimental group 1 (Exp1) and 90mg/kg in the experimental group 2 (Exp2) while the sham group received saline and the control group with regular food and water. The memory retention and duration of step-through latency in male offsprings was determined by passive avoidance apparatus. Neuronal density in hippocampus was established by histopathological methods. Memory and learning indices were investigated by analysis of variance (ANOVA) and a p value less than 0.05 was considered as significant.
Findings: Both experimental groups showed significantly longer step-through latency compared to control group (p<0.05). The average number of pyramidal cells in hippocampal CA1 and granular cells in hippocampal DG were remarkably higher in Exp1 and Exp2 groups compared to control group. The difference between Exp1 and Exp2 for pyramidal cells was found to be significant (p<0.01and p<0.05, respectively).
Conclusion: Silymarin produced a significant increase in learning and memory. Also, our results indicate that silymarin is a dose dependent component. These data may lay a background for application of silybin in treatment of memory impairment diseases.


i wonder if human need such high dose (180 mg/kg) to achieve same effects?

Edited by hippocampus, 11 September 2011 - 08:00 PM.


#19 MrSpud

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Posted 12 September 2011 - 01:19 AM

Siliphos is Indena's phytosome version of Milk Thistle Extract. http://www.phytosome...ic/siliphos.asp
Thisylin is Madaus enhanced water solubility version of Milk Thistle Extract
Both of these are supposedly more bioavailable than regular Milk Thistle Extract but the bioavailability of Thisilyn is only supposed to be 2 times the bioavailability of regular Milk Thistle Extract.

I have heard that some of the generic Milk Thistle Extract's are high in residual solvents, usually acetone. I don't think acetone in trace amounts is considered to be toxic, but it seems counterintuitive to take something to help your liver that has residual solvents in it.

#20 MrSpud

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Posted 12 September 2011 - 01:28 AM

Here's some good info on bioavailability and whatnot for Milk Thistle http://www.salamrese...le_product.html

#21 MrSpud

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Posted 12 September 2011 - 03:02 AM

Heres Indenas Siliphos patent http://www.freepaten...com/4764508.pdf

And this, most likely, the Thisylin Patent http://www.patentgen...nt/6020384.html
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#22 hippocampus

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Posted 12 September 2011 - 01:24 PM

Not sure how this applies to human but anyway interesting:


Evaluation of anxiolytic effects of silymarin extract from Silybum marianum in rats

Author(s): Dr Parichehr Yaghmaei *, Dr Shahrbanoo Oryan, Dr Jalal Solati, Khadijeh Mohammadi and Ali Akbar Salari
Biology Dept., Faculty of Basic Sciences, Islamic Azad University, Science and Research Branch, Tehran, Iran yaghmaei_P@yahoo.com
Study Type: Research | Subject: General

Article abstract:
ABSTRACT Background and Aim: Anxiety is a common psychiatric disorder affecting many people in the society and is associated with clinical symptoms such as tachycardia, sweating, shortness of breath, insensitivity. The objective of this study was to evaluate anxiolytic effects of sylimarin extract in wistar rats. Material and Methods: 35 male Wistar rats with a mean weight of 250±25grams were divided into 5 experimental groups (n=7). Silymarin was purchased from Goldaroo company in Isfahan. The rats received sylimarin with different doses of 35, 70, 140 and 280 mg/Kg for two weeks. The control group received saline orally with the same volume. Then, using elevated plus maze (EPM), 30 minutes after treatment, the behavior of the experimental groups was compared to that of control group. Data were introduced into SPSS software and analyzed by variance analysis. Results: According to the results of this study, sylimarin with the three doses of 35, 70 and 140 mg/Kg caused a statically significant decrease in anxiety, in comparison to the control group. Conclusion: Our data showed that silymarin seems to be a potential and effective anxiolytic agent and can be used for anxiety control. Key words: Anxiety, Silymarin, Milk thistle, Rat Conflict of Interest: Nill Received: July 25, 2010 Accepted: Nov 20, 2010
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#23 John2009

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Posted 20 September 2011 - 01:53 AM

Is there any data on Milk Thistle and male sexual functioning or drive ? The reason I ask is because I read that milk thistle could increase estrogen and decrease Nitric Oxide. If the change in estrogen and nitric oxide production is small and insignificant then I suppose it does not matter.

I've taken milk thistle for a couple of weeks now and have not noticed any problems but I just wondered if anyone else had any experience or was aware of any data in this area.

I had read that milk thistle can increase glutathione production and/or levels in the liver. Is there any reason to think that it would not raise glutathione production / levels throughout the body as well ? Why only in the liver ? I had also read that vitamin D raises glutathione levels in the brain, but again, I'm not sure why it would only raise brain levels without raising levels throughout the body ?

Is there any data on milk thistle and testosterone production or levels ? Does it have any significant effect either way ?

Thanks
John

#24 hav

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Posted 20 September 2011 - 04:28 PM

Milk Thistle certainly seems to be complicated stuff. Here's a study suggesting it inhibits NO:

http://www.ncbi.nlm..../pubmed/8666328

And another study that concludes that at lower doses it increases NO production in macrophages:

http://www.ncbi.nlm....pubmed/20461582

While this other study shows inhibition of NO production as well as activation of SIRT1 and down-regulation of P53:

http://www.ncbi.nlm....pubmed/16946506
http://www.jstage.js.../29/9/1900/_pdf

I've also run across a possible contradiction in Milk Thistle's observed behavior regarding telomerase. Generally, many things that activate SIRT1 are telomerase inhibitors. This study observed that Milk Thistle inhibits telomerase in prostate cancer cells, thereby taking away their immortality:

http://www.ncbi.nlm....pubmed/15076315

But this other study of normal cells found Milk Thistle to be a telomerase activator, delaying their senescence:

http://www.ncbi.nlm....pubmed/20838231

I'm hoping more light gets shed on this because Milk Thistle is something I've always avoided taking when I take Astragalus-related nutrients and cycle in only take when I take my Resveratrol stack.

Howard

#25 John2009

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Posted 20 September 2011 - 08:28 PM

Thanks Howard.

#26 MrHappy

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Posted 21 September 2011 - 10:16 AM

Nice!

#27 maxwatt

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Posted 21 September 2011 - 11:29 AM

...
I've also run across a possible contradiction in Milk Thistle's observed behavior regarding telomerase. Generally, many things that activate SIRT1 are telomerase inhibitors. This study observed that Milk Thistle inhibits telomerase in prostate cancer cells, thereby taking away their immortality:

http://www.ncbi.nlm....pubmed/15076315

But this other study of normal cells found Milk Thistle to be a telomerase activator, delaying their senescence:

http://www.ncbi.nlm....pubmed/20838231

I'm hoping more light gets shed on this because Milk Thistle is something I've always avoided taking when I take Astragalus-related nutrients and cycle in only take when I take my Resveratrol stack.

Howard


There is reason to doubt that SIRT1 inhibits telomerase.
http://www.ncbi.nlm....irt1 telomerase
Most of the studies returned from a pubmed search indicate concomitant upregulation of telomerase with SIRT1 activation, though some have shown the opposite.

#28 John2009

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Posted 24 September 2011 - 06:09 AM

Here is a study I found interesting...

"Silibinin attenuates cognitive deficits and decreases of dopamine and serotonin induced by repeated methamphetamine treatment".

http://www.ncbi.nlm....pubmed/19857526

Looks like it has a positive effect on both serotonin and dopamine ?

I've been taking it for about 20 days and it seems like it has made me feel better, although the effects have been subtle. I would say it has made me feel more calm and less anxious somehow. I have a 50 day supply and I think I will probably try it for at least 100 days to see what it does. I'm taking two pills per day of the nature made brand which gives 280 Mg of a standardized extract yielding about 196 mg of silymarin per day.
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#29 John2009

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Posted 24 September 2011 - 06:35 AM

Here are a few other interesting studies I found...

"Investigating the Potential for Toxicity from Long-Term Use of the Herbal Products, Goldenseal and Milk Thistle"

http://tpx.sagepub.c.../39/2/398.short

Journal of Advanced Pharmacy Education & Research
1:69-79 (2011) Phytotherapeutic properties of milk thistle seeds: An overview

http://www.japer.in/...u 1 July/10.pdf

U.S. patent 7,879,374, B2 talks about milk thistle raising glutathione and SOD levels. Patent relates to a treatment for a hangover.

http://www.google.co...qC48Eue6C5HSXww

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#30 hippocampus

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Posted 25 October 2011 - 09:05 AM

does anybody know whether milk thistle interacts with oral contraceptives?




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