Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells

Prostate cancer (PCa) is the leading cause of cancer-related deaths in men; urgent measures are warranted to lower this deadly malignancy. Silymarin is a known cancer chemopreventive agent, but the relative anticancer efficacy of its constituents is still unknown. Here, we compared the efficacy of 7 pure flavonolignan compounds isolated from silymarin, namely silybin A, silybin B, isosilybin A, isosilybin B, silydianin, isosilydianin, silychristin and isosilychristin, in advanced human PCa PC3 cells. Silybin A, silybin B, isosilybin A, isosilybin B, silibinin and silymarin strongly inhibited the colony formation by PC3 cells (p < 0.001), while silydianin, silychristin and isosilychristin had marginal effect (p < 0.05). Using cell growth and death assays, we identified isosilybin B as the most effective isomer. FACS analysis for cell cycle also showed that silybin A, silybin B, isosilybin A, isosilybin B, silibinin and silymarin treatment resulted in strong cell cycle arrest in PC3 cells after 72 hr of treatment, while the effect of silydianin, silychristin and isosilychristin was marginal (if any). Western blot analysis also showed the differential effect of these compounds on the levels of cell cycle regulators-cyclins (D, E, A and B), CDKs (Cdk2, 4 and Cdc2), CDKIs (p21 and p27) and other cell cycle regulators (Skp2, Cdc25A, B, C and Chk2). This study provided further evidence for differential anticancer potential among each silymarin constituent, which would have potential implications in devising better formulations of silymarin against prostate and other cancers.     

Effect of Silymarinphospholipid Complex on the Liver in Rabbits Maintained on a High-fat Diet

Fifty mongrel rabbits were divided into five equal groups: (1) controls, (2) animals receiving a high-fat diet (HFD), containing cholesteral and coconut oil, (3) HFD + silymarin, (4) HFD + lecithin (L), and (5) HFD + silymarinphospholipid complex (SPC). The experiment lasted 12 weeks. Histopathological alterations due to exposure to HFD were the least advanced in a group of animals maintained on HFD + SPC, compared with group 3 and group 4, and were near normal. A beneficial effect of SPC is most probably due to combined antioxidant (reduction of MDA concentration) and metabolic (fall in cholesterol content in liver homogenate and liver microsomes) properties. These findings suggest that SPC may be an effective agent in the protection against liver damage induced by a high-fat diet.     

Therapeutic potential of silymarin as a natural iron‐chelating agent in β‐thalassemia intermedia

Abnormal iron accumulation in vital organs is one of the major complications of β‐thalassemia intermedia (β‐TI). Silymarin, a flavonolignan isolated from Silybum marianum, significantly decreases the serum ferritin levels of β‐TI patients. This finding suggests silymarin as a safe and effective natural iron‐chelating agent for the treatment of iron‐overloaded conditions.     

水飞蓟素磷脂复合物家兔体内生物利用度的研究

进行了水飞蓟素磷脂复合物家兔体内的生物利用度研究。采用 HPL C法测定血浆中水飞蓟宾游离浓度和总浓度 ,结果显示在选定色谱条件下水飞蓟宾分离良好。水分蓟素原药与复合物服用后总药物浓度的药 -时曲线均出现双峰现象 ,AUC( 0～ 1 2 h) 分别为 5 .5 5和 11.95μg· m l- 1 · h- 1 ,Cmax分别为 0 .76± 0 .5 4、1.0 2± 0 .6 7和 1.6 3± 1.5 0、2 .75± 1.92 μg/ m l,Tmax分别为 1、4 h和 0 .5、2 h;给予水飞蓟素原药后游离药物的血药浓度低于检测限 ,给予复合物后游离药物的药 -时曲线也出现双峰现象 ,Cmax为 0 .99± 1.0 6、0 .35± 0 .31μg/ m l,Tmax为 0 .5、3h,AUC( 0～ 1 2 h) 为2 .4 8μg· ml- 1· h- 1。     

水飞蓟宾降压机理的研究

本实验用麻醉猫、大鼠研究水飞蓟宾(Silybin)产生降压作用的机理。结果发明其降压是非中枢性的,主要由于直接扩张血管所致,与植物神经系统、组胺、前列腺素的释放均无关。     

Herbal antioxidants in dialysis patients: a review of potential mechanisms and medical implications

The consumption of exogenous antioxidants isolated from herbal extracts has shown beneficial effects on ameliorating dialysis-related complications through debilitating oxidative stress and inflammatory process. Many clinical studies available in public databases have reported the improved consequences of dialysis in patients supplemented with herbal antioxidants. Exploration of such data offers great possibilities for gaining insights into the potential mechanisms and medical implications of herbal antioxidants. In this work, the mechanisms and implications of some famous bioactive substances including silymarin, curcumin, resveratrol, emodin, and quercetin on the consequences of dialysis in chronic kidney disease (CKD) patients were explored. The protective features of silymarin are due to the flavonoid complex silybin. Curcumin is an active element from the root of curcuma longa with extensive beneficial properties, including antioxidant, anti-inflammatory activity, and inhibitory effects on cell apoptosis. Resveratrol can reduce the oxidative stress by neutralization of free radicals. Emodin is known as a natural anthraquinone derivative isolated from Chinese herbs. Finally, quercetin has been reported to exhibit several properties including antioxidant, anti-diabetic, analgesic, antihistaminic, antiviral, cholesterol reducer, and renal hemodynamic modulator. However, potential mechanisms and medical implications of the aforementioned herbal antioxidants seem to be more complicated, that is, more studies are required in this field.     

水飞蓟素固体分散体中总黄酮的测定

目的：测定水飞蓟素固体分散体制剂中总黄酮。方法：采用一阶导数紫外分光光度法。结果：以1：3，1：6和1：9药物／载体比例处方制成的固体分散体中总黄酮的量分别为27．72％、15．59％和10．98％。结论：该法可避开空白PEG－6000载体对固体分散体中总黄酮测定的干扰，操作简便，结果准确可靠。     

Effects of silymarin supplementation on blood lipids: A systematic review and meta‐analysis of clinical trials

Dyslipidemia is a leading cause of endothelial dysfunction and cardiovascular disease. Several studies used silymarin as an herbal supplement in hyperlipidemic subjects. The aim of the present systematic review and meta‐analysis was to examine the effect of silymarin supplementation on blood lipids. PubMed, Scopus, Ovid (Cochrane library), ISI Web of Science, and Google Scholar were systematically searched until March 2018 to find intervention studies that examined the impact of silymarin supplementation on blood lipids in adults. Changes in blood lipids and potential sources of between‐study variation were extracted. We run a subgroup analysis to determine potential sources of inter‐study heterogeneity. Ten clinical trials fulfilled the eligibility criteria. Meta‐analysis indicated that silymarin supplementation in combination with other treatments (not silymarin alone) reduced total cholesterol (change: ?25.45 mg/dl; 95% confidence interval [CI] [?47.89, ?3.01 mg/dl]) and low‐density lipoprotein (change: ?28.25 mg/dl; 95% CI [?53.09, ?3.42 mg/dl]). Also, silymarin increased high‐density lipoprotein concentration (change: 4.82 mg/dl; 95% CI [2.01, 7.63 mg/dl]). Blood concentration of triglyceride was significantly after silymarin supplementation in comparison with controls (change: ?22.55 mg/dl; 95% CI [?44.32, ?0.78 mg/dl]). Present systematic review and meta‐analysis revealed that silymarin supplementation in combination with other treatments had a favorable effect on blood lipids.     

Anti-fibrotic effects of Cuscuta chinensis with in vitro hepatic stellate cells and a thioacetamide-induced experimental rat model

Context: Cuscuta chinensis Lam. (Convolvulaceae) has been used as a traditional herbal remedy for treating liver and kidney disorders.

Objective: Anti-fibrotic effects of C. chinensis extract (CCE) in cellular and experimental animal models were investigated.

Materials and methods: HSC-T6 cell viability, cell cycle and apoptosis were analysed using MTT assay, flow cytometry and Annexin V-FITC/PI staining techniques. Thioacetamide (TAA)-induced fibrosis model was established using Sprague Dawley rats (n?=?10). Control, TAA, CCE 10 (TAA with CCE 10?mg/kg), CCE 100 (TAA with CCE 100?mg/kg) and silymarin (TAA with silymarin 50?mg/kg). Fibrosis was induced by TAA (200?mg/kg, i.p.) twice per week for 13 weeks. CCE and silymarin were administered orally two times per week from the 7th to 13th week. Fibrotic related gene expression (α-SMA, Col1α1 and TGF-β1) was measured by RT-PCR. Serum biomarkers, glutathione (GSH) and hydroxyproline were estimated by spectrophotometer using commercial kits.

Results: CCE (0.05 and 0.1?mg/mL) and silymarin (0.05?mg/mL) treatment significantly (p?p?silymarin, respectively) in activated HSC-T6 cells, compared with control group (7.26%). Further, rat primary HSCs showed changes in morphology with CCE 0.1?mg/mL treatment. In in vivo studies, CCE (10 and 100?mg/kg) treatment ameliorated the TAA-induced altered levels of serum biomarkers, fibrotic related gene expression, GSH, hydroxyproline significantly (p?Conclusions: CCE can be developed as a potential agent in the treatment of hepatofibrosis.