Presence of Mycotoxins in Milk Thistle (Silybum marianum) Food Supplements: A Review

The consumption of herbal-based supplements, which are believed to have beneficial effects on human health with no side effects, has become popular around the world and this trend is still increasing. Silybum marianum (L.) Gaertn, commonly known as milk thistle (MT), is the most commonly studied herb associated with the treatment of liver diseases. The hepatoprotective effects of active substances in silymarin, with silybin being the main compound, have been demonstrated in many studies. However, MT can be affected by toxigenic micro-fungi and contaminated by mycotoxins with adverse effects. The beneficial effect of silymarin can thus be reduced or totally antagonized by mycotoxins. MT has proven to be affected by micro-fungi of the Fusarium and Alternaria genera, in particular, and their mycotoxins. Alternariol-methyl-ether (AME), alternariol (AOH), beauvericin (BEA), deoxynivalenol (DON), enniatin A (ENNA), enniatin A₁ (ENNA₁), enniatin B (ENNB), enniatin B₁ (ENNB₁), HT-2 toxin (HT-2), T-2 toxin (T-2), tentoxin (TEN), and zearalenone (ZEA) seem to be most significant in MT-based dietary supplements. This review focuses on summarizing cases of mycotoxins in MT to emphasize the need for strict monitoring and regulation, as mycotoxins in relation with MT-based dietary supplements are not covered by European Union legislation.     

水飞蓟素新型纳米制剂的研究进展

综述近年来水飞蓟素新型纳米制剂的研究进展。目前纳米传递系统可通过增加水飞蓟素的溶出速率(如:纳米混悬液、β-环糊精包合物、自乳化药物传递系统、固体分散体和微粉化技术)、提高生物膜的通透性(如:磷脂复合物、纳米结构脂质载体)以及其他方式(如:胶束、介孔二氧化硅纳米粒、聚酰胺-胺型树枝状高聚物)等,促进水飞蓟素的吸收、提高其生物利用度。对提高难溶性药物的生物利用度具有一定的指导意义。     

Improved dissolution and bioavailability of silymarin delivered by a solid dispersion prepared using supercritical fluids

The objective of this study was to improve the dissolution and bioavailability of silymarin (SM). Solid dispersions (SDs) were prepared using solution-enhanced dispersion by supercritical fluids (SEDS) and evaluated in vitro and in vivo, compared with pure SM powder. The particle sizes, stability, and contents of residual solvent of the prepared SM-SDs with SEDS and solvent evaporation (SE) were investigated. Four polymer matrix materials were evaluated for the preparation of SM-SD-SEDS, and the hydrophilic polymer, polyvinyl pyrrolidone K17, was selected with a ratio of 1:5 between SM and the polymer. Physicochemical analyses using X-ray diffraction and differential scanning calorimetry indicated that SM was dispersed in SD in an amorphous state. The optimized SM-SD-SEDS showed no loss of SM after storage for 6 months and negligible residual solvent (ethanol) was detected using gas chromatography. In vitro drug release was increased from the SM-SD-SEDS, as compared with pure SM powder or SM-SD-SE. In vivo, the area under the rat plasma SM concentration-time curve and the maximum plasma SM concentration were 2.4-fold and 1.9-fold higher, respectively, after oral administration of SM-SD-SEDS as compared with an aqueous SM suspension. These results illustrated the potential of using SEDS to prepare SM-SD, further improving the biopharmaceutical properties of this compound.     

Effect of goat milk on hepatotoxicity induced by antitubercular drugs in rats

Aim of the present study was to assess the hepatoprotective activity of goat milk on antitubercular drug-induced hepatotoxicity in rats. Hepatotoxicity was induced in rats using a combination of isoniazid, rifampicin, and pyrazinamide given orally as a suspension for 30 days. Treatment groups received goat milk along with antitubercular drugs. Liver damage was assessed using biochemical and histological parameters. Administration of goat milk (20 mL/kg) along with antitubercular drugs (Group III) reversed the levels of serum alanine aminotransferase (82 ± 25.1 vs. 128.8 ± 8.9 units/L) and aspartate aminotransferase (174.7 ± 31.5 vs. 296.4 ± 56.4 units/L, p < 0.01) compared with antitubercular drug treatment Group II. There was a significant decrease in serum alanine aminotransferase (41.8 ± 4.1 vs. 128.8 ± 8.9 units/L, p < 0.01) and aspartate aminotransferase (128.8 ± 8.54 vs. 296.4 ± 56.4 units/L, p < 0.001) levels in Group IV (goat milk 40 mL/kg) compared with antitubercular drug treatment Group II. Goat milk (20 mL/kg and 40 mL/kg) was effective in reversing the rise in malondialdehyde level compared with the antitubercular drug suspension groups (58.5 ± 2 vs. 89.88 ± 2.42 μmol/mL of tissue homogenate, p < 0.001 and 69.7 ± 0.78 vs. 89.88 ± 2.42 μmol/mL of tissue homogenate, p < 0.001, respectively). Similarly, both doses of milk significantly prevented a fall in superoxide dismutase level (6.23 ± 0.29 vs. 3.1 ± 0.288 units/mL, p < 0.001 and 7.8 ± 0.392 vs. 3.1 ± 0.288 units/mL, p < 0.001) compared with the group receiving antitubercular drugs alone. Histological examination indicated that goat milk reduced inflammation and necrotic changes in hepatocytes in the treatment groups. The results indicated that goat milk prevented the antitubercular drug-induced hepatotoxicity and is an effective hepatoprotective agent.     

水飞蓟素胶囊溶出度一致性评价研究

考察试制品水飞蓟素胶囊在四种不同溶出介质中的溶出状况,对比参比药物作一致性评价研究,同时与原料药作比较,分别考察不同制剂在不同溶出介质中六种组份的溶出度改善与变化情况。结果显示,试制品与参比药物对比,各试验条件下,各组份f2因子均大于50,显示二者溶出度具有相似性。     

Biochemical and immunological basis of silymarin effect,a milk thistle (Silybum marianum) against ethanol-induced oxidative damage

Ethanol metabolism induces generation of excessive amount of reactive oxygen species (ROS) which results in immune dysfunction. We examined the efficacy of silymarin on ethanol-induced oxidative stress, immunomodulatory activity, and vascular function in mice blood. Effectiveness of silymarin was compared with potent antioxidant ascorbic acid. In the present study, 8- to 10-week-old male BALB/c mice (20–30 g) were divided into the four groups of six each. One group were fed with ethanol (1.6 g/kg body weight), while second group were fed with ethanol (1.6 g/kg body weight) and silybin (250 mg/kg body weight), and the third group were exposed to ethanol (250 mg/kg body weight) and ascorbic acid (250 mg/kg body weight) per day for 12 weeks. The control group was fed with isocaloric glucose solution instead of ethanol. Ethanol exposure significantly increased thiobarbituric acid reactive substance (TBARS) and nitrite levels besides glutathione-S-transferase (GST) activity, and significantly decreased reduced glutathione (GSH) content and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) in whole blood hemolyzate, while silymarin treatment significantly normalized these altered parameters. Silymarin significantly prevented ethanol-induced, elevated activities of interleukin (IL)-10, tumor necrosis factor (TNF)-α, γ interferon (IFN-γ), vascular endothelial growth factor (VEGF)-A, and transforming growth factor (TGF)-β1, as well as decreased IL-4 activity in mice blood. These results were comparable with the activity of ascorbic acid.     

Silymarin inhibits cervical cancer cell through an increase of phosphatase and tensin homolog

Silymarin is an active constituent contained in the seeds of the milk thistle plant and is widely used as a hepatic protection agent due to its antioxidant-like activity. In the present study we evaluated the potential action of silymarin against cervical cancer and investigated its mechanism of action. Treatment of cervical cancer cells (C-33A) with silymarin resulted in a significant decrease in cell viability. Silymarin induced apoptosis through the modulation of Bcl-2 family proteins and activation of caspase 3. Silymarin also inhibited the phosphorylation of Akt with an increase in expression of phosphatase and tensin homolog (PTEN). We also observed that silymarin suppressed C-33A cell invasion and wound-healing migration in a concentration-dependent manner. Western-blot analysis showed that silymarin significantly inhibited the expression of matrix metalloproteinase-9 (MMP-9) in C-33A cells. Furthermore, we applied siRNA to lower the PTEN gene, which diminished the anticancer actions of silymarin. Taken together, these results show that silymarin has the potential to suppress the survival, migration and invasion of C-33A cancer cells; thus, it could be developed as a promising agent for the treatment of cervical cancer in the future.     

复方水飞蓟素-丹参素滴丸的制备工艺优选

目的:筛选固体分散体技术制备水飞蓟素-丹参素复方滴丸的最佳工艺条件。方法:采用聚乙二醇4000,聚乙二醇6000和Poloxamer 188为固体分散体载体材料,熔融法制备复方水飞蓟素-丹参素滴丸。以丸重差异、圆整度、溶出度为指标,采用单因素试验考察滴速、冷却剂与冷却温度等因素对滴丸成型的影响;通过正交试验优选基质组成、药物与基质配比、药液温度、滴距等制备工艺条件。结果:最佳制备工艺条件为基质组成PEG 4000-PEG 6000-Poloxamer 188为5∶5∶1,药物与基质配比1∶2,滴制时药液温度90℃,滴距5 cm,滴速40滴/min,二甲基硅油为冷却剂,冷却温度(10～15)℃。结论:优选的复方水飞蓟素-丹参素滴丸制备工艺合理可行,对主药有良好的增溶效果。     

Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part I. Silymarin and its flavonolignans

Silymarin, an extract of fl avonolignans from the dried fruits of milk thistle (Silybum marianum L. Gaertneri) and its constituents silibinin, dehydrosilibinin, silychristin and silydianin were tested for protective effects on rat cardiomyocytes exposed to doxorubicin. Silymarin and individual fl avonolignans did not exert cytotoxicity in the range 25-100 micro m (incubation 9 h). Dehydrosilibinin was tested only at 25 micro m concentration due to its low solubility. All substances increased the cell ATP level. Silymarin and fl avonolignans displayed a dose-dependent cytoprotection against doxorubicin (100 micro m, incubation 8 h). The protective effects of silymarin, silibinin, dehydrosilibinin and silychristin were comparable to that of dexrasoxane, while silydianin exerted the best protective effect. The ability of silymarin complex and its components to protect cardiomyocytes against doxorubicin-induced oxidative stress is due mainly to their cell membrane stabilization effect, radical scavenging and iron chelating potency.