Расторопши: семена ранней потенциальных
Silymarin in Clinical Trials
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- Pharmacology and Metabolism of Silymarin
- Conclusions
Silymarin in Clinical TrialsHuman clinical studies have demonstrated that milk thistle extract has significant hepatoprotective, antidiabetic, and cardioprotective effects. The efficacy of silymarin is being evaluated in cancer patients either alone or in combination with other chemotherapeutic agents. Several doses of silymarin have been tested both alone and in conjunction with other drugs in several populations. Silipide, a silibinin formulation, was given orally to patients with colorectal adenocarcinoma at doses of 360, 720, or 1440 mg daily for 7 days and high levels of silibinin were achieved in colorectal mucosa of the patients [61]. Our group has also recently completed a phase-I clinical trial with silibinin in prostate cancer patients. Silibinin phytosome (SiliphosR), a commercial preparation of silibinin, at a dose of 13g, divided in 3 daily doses, appears to be well tolerated in patients with advanced prostate cancer. We also found over 100μM of plasma levels of free silibinin in patients, though this level was not sustained [62]. Now, we are in the process of starting a pilot Phase II clinical trial to assess the effect of silibinin administration on prostate cancer progression using surrogate biomarkers as endpoints. Silymarin was used (along with soy, lycopene and antioxidants) in a phase III clinical trials to delay prostate specific antigen progression after prostatectomy and radiotherapy in prostate cancer patients [63]. Chemotherapeutic agents provide significant protective effects against many cancers; however it has been shown that hepatotoxicity is a frequent even caused by these drugs. Studies have shown that milk thistle has been used in treatment of chemotherapy induced hepatotoxicity and protecting the liver during chemotherapy. Invernizzi et al [64] have shown the use of silymarin in a 34-year-old woman with promyelocytic leukemia. The investigators administered 800 mg/d silymarin during the patient’s methotrexate and 6-mercaptopurine chemotherapy. During the 4 months of treatment with silymarin, the patient had normal liver transaminase levels and there was no further interruption of therapy. Milk thistle supplementation in children with acute lymphopblastic leukemia (ALL) and higher hepatic toxicity has been associated with decrease in liver transaminases level and greater than 50% reduction in total bilirubin. Studies have demonstrated that silymarin may play a role in adjuvant cancer therapy. In vitro studies have shown that silymarin increased daunomycin accumulation, potentiated doxorubicin toxicity and inhibited efflux of these drugs from cancer cells. In a nonrandomized study, patients with brain metastases receiving stereotactic radiotherapy with omega 3 fatty acids and silymarin had longer survival times and a decreased number of radionecroses [65]. Future clinical studies are warranted to examine silymarin activity in multifatorial mechanisms of action, well-designed clinical trials and clarification of adverse effects. Pharmacology and Metabolism of SilymarinPreclinical and clinical studies have examined the pharmacokinetics, pharmacodyanamics and metabolism of silymarin. The in vivo effectiveness of silymarin flavonolignans depends on bioavailability and achieving therapeutics concentrations in the organs of interest. The components of the silymarin are poorly soluble in water and studies in both preclinical and clinical have shown only ng/ml in plasma following oral administration of powdered extracts. However, pharmacokinetics studies have shown that bioavailability of silybin has been increased when combines with phosphaditylcholine as silipide, Siliphos or IdB 1016. Barzaghi et al [66] have reported on a trial in nine healthy volunteers receiving IdB 1016 (equivalent to 120 mg silybin) for 8 consecutive days, and showed 340ng/ml and 183 ng/ml silybin plasma levels from day 1 to day 8. Most of the silybin present in the systemic circulation was in conjugated form. Less than 3% of the administered dose was accounted for by urinary recovery of total silybin. To increase the bioavailability of silymarin, Wu et al [67] developed lipid-based self-microemulsifying drug delivery system (SMEDDS). In this study, Wu et al [67] compared the bioavailability of silymarin SMEDDS with that in solution and suspension. After intragastric administration to rabbits, the bioavailability of silymarin SMEDDS was 1.88-and 48.82-fold that of silymarin solution and suspension. Kim et al [68] examined the comparative bioavailability of a Liverman capsule to a Legalon capsule and a silymarin tablet in 24 healthy Korean male volunteers, who received a silybin dose of 120 mg in a 3 × 3 crossover study. They found that oral bioavailability of siibinin after liverman capsule was significantly faster and greater than that after legalon capsule and silymarin tablet. IdB 1016 (silipide), a silibinin phosphoditylcholine formulation showed improved oral availability compared with silymarin, achieving peak plasma levels in healthy volunteers. In another study, patients with colorectal carcinoma received IdB 1016 at dosages of 360, 720, or 1440mg of silibinin daily for 7 days. The achieved levels of silibinin were 0.3 to 4μmol/L in the plasma, 0.3 to 2.5 nmol/g in the liver, and 20 to 141 nmol/g in colorectal tissue [61]. ConclusionsThis mini review briefly summarizes multi-targeted chemopreventive and interventive targets and mechanisms of silymarin/silibinin in various in vitro and in vivo cancer models. All these results validate pharmacological safety of silymarin, which is needed for effective chemopreventive as well as chemotherapeutic agent. Silymarin exerts its anticancer effects by multiple molecular mechanisms that could block all stages of carcinogenesis, initiation, promotion and progression. In particular, anti-invasive and anti-metastatic effects of silymarin authenticate its possible usefulness as preventive and therapeutic agent in the treatment of more advanced and aggressive forms of cancer. Clinical studies have shown that silymarin treatment in combination with chemotherapeutic agents reduces the toxicity associated with chemotherapy. Additional clinical research is warranted to evaluate further the chemopreventive as well as chemotherapeutic effects of silymarin and its analogues against various human cancers. Интеграция пищевые добавки в cancer care. Многие исследования подтверждают, что большинство пациентов, перенесших рак терапия с использованием самостоятельно выбранных форм дополнительных методов лечения, в основном БАДы. К сожалению, пациенты часто не сообщают их использования добавок для их поставщиков. Отказ врачей эффективно общаться с пациентами на этом его использование может привести к потере доверия в терапевтических отношениях и в выборе пациентами вредными, бесполезными или неэффективными и дорогостоящими нетрадиционной терапии при эффективной интегративной вмешательства могут существовать. Плохая связь может также привести к ухудшению, самостоятельности пациента и самоэффективность и тем самым мешать заживлению ответ. Быть открытым с точки зрения пациента, и чувствительны к его потребности в автономии и расширения прав и возможностей, врачи должны сменить свои взгляды. Пожалуй, оптимальный подход, чтобы обсуждать факты и неопределенность с пациентом, в целях достижения взаимно осознанное решение. Сегодня информированные пациенты действительно ценим врачей, которые ценят их как равноправных участников в создании их собственного здоровья выбор. Чтобы достигнуть взаимно осознанное решение об использовании этих добавок в клинической практике Комитета общества интегративной онкологии взяла на себя задачу предоставления информации для врачей, которые хотят обсудить эти вопросы со своими пациентами. Список ведущих добавки, которые имеют лучшие предложения выгода была построена ведущих исследователей и клиницистов, которые имеют опыт в использовании этих добавок. Этот список содержит куркумин, глютамин, витамин D, Маитаке грибы, рыбий жир, зеленый чай, расторопша, Астрагал, мелатонин, и пробиотики. Список включает в себя основную информацию о каждой добавки, такие как фактических данных об эффективности и клинических испытаний, побочные эффекты, взаимодействия лекарств. Информация, был построен, чтобы предоставить актуальную базу знаний, так что врачи и другие медицинские работники будут в курсе добавки, и быть в состоянии обсуждать реалистичные ожидания и потенциальные выгоды и риски. Integr Cancer Ther. 2013 Sep;12(5):369-84. doi: 10.1177/1534735412473642. Epub 2013 Feb 25. жүктеу/скачать 2.54 Mb. Достарыңызбен бөлісу:
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