Study on the pharmacological effects of Silymarin extracted from introduced milk thistle fruits (Silybum marianum (L.)) collected at Sa Pa and Ha Noi in June 2002. Results: the silymarin product had chronic anti-inflammatory effects in experimental tumor model, inhibited formation of granuloma with the rate of 28.69% compared with control rats; had hepatic protection effect, decreased GPT enzyme activity and serum bilirubine of rats with 36.19% and 38.18%, respectively, in CCl4 poisoned model compared with control rats; increased bile flow up 32.25% compared with this before receiving silymarin and 49.88% compared with rats without drug, but didn’t change the bile quality
Silymarin ; Fruit ; Pharmacology

Silymarin is the standardized extract from Silybum marianum which consists mainly of flavonoids and polyphenols. It is highly regarded for its hepatoprotective ability. Silybin B is a flavonolignan and one of the active components of silymarin. The content of silybin B in various parts of S. marianum was analyzed by HPLC-UV. Results show that the extract of seeds contain the highest amount of silybin B (7.434 mg/g DW). The petioles of S. marianum showed a low content of silybin B. This study revealed that seeds of S. marianum contain high amount of silybin B and could be a good source of the compound.
Flavonoids ; Milk Thistle ; Polyphenols ; Silymarin

BACKGROUND: The first line of anti-tuberculosis (TB) drugs are the most effective standard of drugs for TB. However, the use of these drugs is associated with hepatotoxicity. Silymarin has protective effects against hepatotoxicity of anti-TB drugs in animal models. This study aims to investigate the protective effect of silymarin on hepatotoxicity caused by anti-TB drugs. METHODS: This is a prospective, randomized, double-blind and placebo-controlled study. Patients were eligible if they were 20 years of age or order and started the first-line anti-tuberculosis drugs. Eligible patients were randomized for receiving silymarin or a placebo for the first 4 weeks. The primary outcome was the proportion of patients who showed elevated serum liver enzymes more than 3 times the upper normal limit (UNL) or total bilirubin (TBil) > 2× UNL within the first 8 weeks of anti-TB treatment. RESULTS: We enrolled a total of 121 patients who silymarin or a placebo to start their anti-TB treatment, for the first 8 weeks. The proportions of elevated serum liver enzymes more than 3 times of UNL at week 2, week 4, and week 8 did not show any significant difference between the silymarin and placebo groups, at 0% versus 3.6% (p>0.999); 4.4% versus 3.6% (p>0.999); and 8.7% versus 10.8% (p=0.630), respectively. However, patients with TBil >2× ULN at week 8 were significantly low in the silymarin group (0% versus 8.7%, p=0.043). CONCLUSION: Our findings did not show silymarin had any significant preventive effect on the hepatotoxicity of anti-TB drugs.
Bilirubin ; Humans ; Liver ; Models, Animal ; Prospective Studies ; Silymarin* ; Tuberculosis

The kiwi (Actinidia deliciosa) is well known to contain anti-oxidants. In this study, we investigated the anti-oxidant effects of kiwi extract on carbon tetrachloride (CCl4) induced liver injury in BALB/c mice. The radical scavenging effect of 80% methanol extract of Halla-Gold kiwi was observed. For the animal study, mice were randomly divided into four groups: normal group, CCl4-induced model group, kiwi extract administered group, and silymarin treated group. The kiwi extract was provided daily for 10 days. At the 24 h after last administration, CCl4 was injected. The kiwi extract showed strong inhibitory effect of DPPH radicals and superoxide scavenging. In animal study, administration of CCl4 resulted in significantly elevated plasma levels of ALT and AST but they decreased in kiwi-extract pretreated group. Anti-oxidant enzymes such as GSH-px and GSH-rd were restored in the kiwi extract treatment group. Histopathological degeneration was also prevented in the kiwi extract treated group compared with of the control group, which exhibited CCl4-induced hepatotoxicity. On the basis of the obtained results, it can be concluded that kiwi extract showed protective effects, not only as anti-oxidant effects, but also in the protection of hepatotoxicity in CCl4-intoxicated mice.
Animals ; Antioxidants ; Carbon ; Carbon Tetrachloride ; Cytochrome P-450 CYP2E1 ; Fruit ; Liver ; Methanol ; Mice ; Plasma ; Silymarin ; Superoxides

OBJECTIVETo prepare silymarin nanosuspension and lyophilized power for enhancing the dissilution of poorly soluble drugs.

METHODThe precipitation technique was adapted to produce the silymarin nanosuspensions respectivly applying Tween 80, SDS and Poloxamer188 as stabilizers. The lyophilized formula contained 5% mannitol as cryoprotectant. Particle size, Polydispersity index and Zeta potential were detected by Mastersizer nano ZS (Malvern England). Morphological character was observed with Transmission Electron Microscopy. The product's structure was performed with X-ray diffractometer.

RESULTThe silymarin nanosuspension was successfully prepared, in which the drug particle size was about 100-300 nm,and the particles had ball-like shape and good dispersive properties.

CONCLUSIONThis study provided potential for the neotype dosage form development of the Chinese Traditional Medicine.

Chemistry, Pharmaceutical ; methods ; Freeze Drying ; Nanoparticles ; chemistry ; Particle Size ; Silymarin ; chemistry ; Solubility ; Suspensions ; chemistry

AIMTo investigate the lattice mechanisms involved in the increased dissolution effect of polyethylene glycol (PEG 6,000) dispersion system on poorly soluble drug silymarin (SILY).

METHODSFusion method was used to prepare the solid dispersions of SILY with PEG 6,000. Evaluation of the improvement of dissolution was performed with dissolution studies in vitro. X-ray powder diffraction combined with diffraction peak pattern-fitting procedure were applied to quantitatively analyze the changes of lattice parameters. The interaction of SILY and PEG 6,000 was also determined with Fourier transform-infrared (FT-IR) spectroscopy.

RESULTSThe dissolution rate of SILY was considerably increased when formulated in solid dispersion of PEG 6,000 as compared to pure SILY. The datum from the X-ray diffraction showed the changes in the lattic spacings and particular diffraction peaks (position and the intensity) of PEG 6,000 and SILY. These could explain the increased rate of SILY released from solid dispersion system. The information of FT-IR spectroscopy showed the absence of well-defined drug-polymer interaction.

CONCLUSIONThe dissolution improvement of poorly soluble SILY from solid dispersion of PEG 6,000 can be illuminated by the changes of the lattice parameters of PEG 6,000 and the drug.

Chemistry, Pharmaceutical ; Crystallization ; Crystallography, X-Ray ; Drug Carriers ; Polyethylene Glycols ; chemistry ; Silymarin ; administration & dosage ; chemistry ; Solubility

OBJECTIVETo test the dissolution rate of silymarin dropping pill as well as to be compared with other three commercial products of the silymarin.

METHODBy UV spectrophotometry, we studied the dissolution conditions of silymarin dropping pill and compared its dissolution rate with Yiganling tablets (film-coating, sugar-coating) and Legalon capsule which are available in the market.

RESULTThe dissolution parameters T50 and Td of silymarin dropping pill, Yiganling tablet (film-coating), Yiganling tablet (sugar-coating) and Legalon capsule are 6.78, 9.85 min, 51.01, 73.78 min, 74.35, 86.97 min and 53.10, 72.65 min.

CONCLUSIONThe dissolution rate of silymarin dropping pill is superior to that of two kinds of Yiganling tablets and Legalon capsule.

Capsules ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Silymarin ; administration & dosage ; chemistry ; Solubility ; Spectrophotometry, Ultraviolet ; Tablets

PURPOSE: This study was conducted to evaluate the clinical efficacy of pharmacologic treatment of amatoxin poisoning patients. METHODS: Literature was accessed through PubMed, EMBASE, Cochrane library, KoreaMed, KISS and KMBASE. Studies relevant to human use of pharmacologic therapy including silymarin, penicillin and N-acetylcysteine (NAC) for amanita poisoning were included. Case reports, letters, editorials and papers with insufficient information were excluded. Comparison of clinical outcomes (especially mortality and liver transplantation rate) in each study was analyzed. RESULTS: The final analysis included 13 retrospective studies. None of these studies showed direct comparisons of individual agents. Among 12 studies comparing silymarin vs penicillin, eight showed clinical superiority of silymarin. Among eight studies comparing silymarin with NAC, six showed clinical superiority of silymarin. Among seven studies of NAC vs penicillin, five showed clinical superiority of NAC. CONCLUSION: This systematic review suggested that clinical superiority of various pharmacological agents used to treat amatoxin poisoning is debatable. Nevertheless, the available evidence suggests it is reasonable to consider combinations of multiple agents for patients with amanita poisoning. Further studies are required to establish a treatment regimen for amanita poisoning.
Acetylcysteine* ; Amanita ; Humans ; Liver Transplantation ; Mortality ; Penicillins* ; Poisoning* ; Retrospective Studies ; Silymarin* ; Treatment Outcome

Silymarin from milk thistle (Silybum marianum) has been reported to show an anti-cancer activity. In previous study, we reported that silymarin induces cyclin D1 proteasomal degradation through NF-κB-mediated threonine-286 phosphorylation. However, mechanism for the inhibition of Wnt signaling by silymarin still remains unanswered. Thus, we investigated whether silymarin affects Wnt signaling in human colorectal cancer cells to elucidate the additional anti-cancer mechanism of silymarin. Transient transfection with a TOP and FOP FLASH luciferase construct indicated that silymarin suppressed the transcriptional activity of β-catenin/TCF. Silymarin treatment resulted in a decrease of intracellular β-catenin protein but not mRNA. The inhibition of proteasome by MG132 and GSK3β inhibition by SB216763 blocked silymarin-mediated downregulation of β-catenin. In addition, silymarin increased phosphorylation of β-catenin and a point mutation of S33Y attenuated silymarin-mediated β-catenin downregulation. In addition, silymarin decreased TCF4 and increased Axin expression in both protein and mRNA level. From these results, we suggest that silymarin-mediated downregulation of β-catenin and TCF4 may result in the inhibition of Wnt signaling in human colorectal cancer cells.
Colorectal Neoplasms* ; Cyclin D1 ; Down-Regulation ; Humans* ; Luciferases ; Milk Thistle ; Phosphorylation ; Point Mutation ; Proteasome Endopeptidase Complex ; RNA, Messenger ; Silymarin* ; Transfection

PURPOSE: Chemotherapies for breast cancer generally have strong cellular cytotoxicity and severe side effects. Thus, significant emphasis has been placed on combinations of naturally occurring chemopreventive agents. Silibinin is a major bioactive flavonolignan extracted from milk thistle with chemopreventive activity in various organs including the skin, prostate, and breast. However, the mechanism underlying the inhibitory action of silibinin in breast cancer has not been completely elucidated. Therefore, we investigated the effect of silibinin in MCF-7 human breast cancer cells and determined whether silibinin enhances ultraviolet (UV) B-induced apoptosis. METHODS: The effects of silibinin on MCF-7 cell viability were determined using the MTT assay. The effect of silibinin on PARP cleavage, as the hallmark of apoptotic cell death, and p53 protein expression in MCF-7 cells was analyzed using Western blot. The effect of silibinin on UVB-induced apoptosis in MCF-7 cells was analyzed by flow cytometry. RESULTS: A dose- and time-dependent reduction in viability was observed in MCF-7 cells treated with silibinin. Silibinin strongly induced apoptotic cell death in MCF-7 cells, and induction of apoptosis was associated with increased p53 expression. Moreover, silibinin enhanced UVB-induced apoptosis in MCF-7 cells. CONCLUSION: Silibinin induced a loss of cell viability and apoptotic cell death in MCF-7 cells. Furthermore, the combination of silibinin and UVB resulted in an additive effect on apoptosis in MCF-7 cells. These results suggest that silibinin might be an important supplemental agent for treating patients with breast cancer.
Apoptosis ; Blotting, Western ; Breast ; Breast Neoplasms ; Cell Death ; Cell Survival ; Humans ; MCF-7 Cells ; Milk Thistle ; Prostate ; Silymarin ; Skin