Расторопши: семена ранней потенциальных

Uses and Effectiveness

LIVER DISEASE

In a six-month double-blind study26 of 36 patients with chronic alcoholic liver disease, the group given Legalon showed normalization of their bilirubin, aspartate transaminase and alanine transaminase serum levels, and also showed improvement in histology. These effects did not occur in the placebo group. In another study,27 106 patients with mild acute and subacute liver disease characterized by elevated serum transaminase levels were randomized to receive silymarin or placebo. Of the 97 patients who completed the four-week study, there was a statistically significant greater decrease in transaminase levels in the silymarin group. In addition, results of a smaller study28 of 20 patients with chronic active hepatitis randomized to placebo or silybin showed that the milk thistle group had significantly lower transaminase, bilirubin, and gamma-glutamyltranspeptidase levels than the placebo group. This study used a complex of silybin with phosphatidylcholine, which appears to increase bioavailability.

Other studies have not duplicated these positive effects. In a study29 of 200 patients with alcoholic cirrhosis, there were no differences in time to death or progression to liver failure in the 125 patients who completed 24 months of therapy. Similarly, in a study30 of 72 patients with alcoholic liver disease, there were no differences in mortality or laboratory values between the placebo and silymarin groups. Finally, a three-month study31 of 116 patients with histologically proven alcoholic hepatitis randomized to placebo or silymarin showed no significant differences in serum transaminase activity or histologic fibrosis scores.

Two meta-analyses of milk thistle for liver disease32,33 detail the major limitations of prior studies and conclude that data are insufficient to support its use at this time. The two main limitations are the heterogeneity of the study populations, caused by lack of precise inclusion and exclusion criteria and the noncomparability of doses received. Most studies did not report or use objective criteria to determine the severity and etiology of cirrhosis and did not control for confounding factors such as infection with hepatitis B or C and ongoing alcohol intake. In addition, the trials vary considerably in duration, ranging from one week to 41 months, without agreement on the minimum duration needed to see effect. The effect of silymarin is thought to be dose-dependent, and it is not known whether the bioavailability of different formulations is equivalent.6,7 Because the studies used different products, it is not known whether participants in the different studies received equivalent doses. These limitations make comparisons of studies difficult to interpret. Efforts are under way to isolate, semisynthesize, and extensively characterize the biologic activities of the flavonolignans that constitute silymarin.34 Developing products that contain standardized percentages of precise ratios of the components of silymarin will improve the ability to test its effectiveness.

CYTOPROTECTANT

Studies of the use of milk thistle as a cytoprotectant in humans have been limited. In one study,35 49 of 200 workers exposed to toluene or xylene for five to 20 years developed persistent elevations in transaminase levels; 30 of these heterogeneous patients were treated with Legalon, whereas the others were not treated. In the Legalon group, transaminase activity decreased and platelet count increased when compared with the untreated group. Patients two to 21 years of age with acute lymphoblastic leukemia who are receiving hepatotoxic chemotherapy are being recruited for a second phase randomized pilot trial of silymarin.

ANTICARCINOGEN

Researchers are investigating the use of milk thistle’s active ingredients for the prevention and treatment of cancer. Two additional animal studies on prostate cancer chemoprevention and treatment are ongoing, and a third phase trial in human prostate cancer patients with rising prostate-specific antigen also is under way.

AMANITA PHALLOIDES POISONING

The A. phalloides mushroom, called the “death cap,” produces severe nausea, vomiting, and watery diarrhea within five to 12 hours of ingestion. This often causes hypovolemia and hypoglycemia. Silymarin inhibits the binding of the toxins in the mushroom to hepatocytes and interrupts the enterohepatic circulation of the toxins.36 Several journals have published case reports of silymarin treatment (intravenously and orally) for A. phalloides poisoning in humans, but the largest series37 followed only 18 patients. In every case, silymarin was used in combination with other agents, usually being added when standard treatment appeared to fail. The relative contribution of silymarin to these treatment regimens is unknown. The intravenous form of silymarin was used in these studies, but it is not available in the United States.

ADVERSE EFFECTS AND INTERACTIONS

The Agency for Healthcare Research and Quality reviewed the effects of milk thistle on liver disease and cirrhosis,32 noting that serious adverse reactions are virtually unheard of. The most common reported complaints were gastrointestinal disturbances, but the overall incidence was no different from placebo. Allergic reactions, ranging from pruritus and rash to eczema and anaphylaxis, are rare.

Drug interactions do not appear to be problematic. Silybin inhibits the activities of CYP2D6, CYP2E1, and CYP3A4, but at physiologic concentrations far higher than those given clinically.38 In a study39 of 10 healthy volunteers, administration of 175 mg of milk thistle three times daily for three weeks had no significant effect on concomitantly administered indinavir (Crixivan).

DOSAGE

Most clinical trials have used daily dosages of 420 to 480 mg silymarin, divided into two or three doses daily. Until the specific effects of each of the flavonolignans is known and products are available that contain standardized ratios of these components, the optimal dosage will remain unknown. Table 1 outlines the efficacy, safety, tolerability, dosage, and cost of milk thistle.

И предклинические эффективность силибинин в предотвращении кожи рак.

Эукариотические клеточные механизмы, в том числе генома сталкиваются с постоянной проблемой из окружающей среды вредных веществ, а также от продуктов собственного метаболизма. Наша кожа-это самый важный барьер. Он защищает нас от ксенобиотиков и генотоксических агентов, в том числе ультрафиолетового (УФ) излучения солнца и потенциальных канцерогенов, которые славятся кожи, вызывая рак. Подъем в номера-меланома кожи, рак (НМСК), который диагностируется у более чем миллиона человек ежегодно в одних только Соединенных Штатах, и также распространено и в других западных странах. Помимо солнцезащитных кремов, проведение химиопрофилактики кожи, рака с помощью природных нетоксичных соединений предлагается эффективная стратегия предотвращения случаев кожного рака. Наши обширные исследования на животных на силибинин, нетоксичных биологически активных компонентов в расторопши, предполагают, что она имеет мощный потенциал, чтобы предотвратить кожу от рака заболеваемость, промоции и прогрессии в ответ на химические канцерогены и опухолевых промоторов, а также УФ-излучения. Наши данные позволяют предположить, что силибинин имеет несколько мишеней в клетке, и может быть защитной против вредного воздействия цитотоксических агентов, таких как активные формы кислорода и воспаления. Далее, силибинин модулирует митогенных и выживания сигнализации, р53, Cip1/р21 и других молекул, регулирующих клеточный цикл, чтобы предотвратить УФ-индуцированный канцерогенез кожи. Наши текущие исследования также показывают положительный эффект силибинин на ремонт УФ-индуцированных повреждений ДНК в мышь кожу. В целом, защитную эффективность силибинин против кожи рак поддерживается звук механистическое обоснование в животных и культуры клеток исследования, и предполагает возможность его применения для человека.

Eur J Cancer. 2005 Sep;41(13):1969-79.

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