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

Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; Liver ; drug effects ; pathology ; Mice ; Silymarin ; pharmacology ; Ursodeoxycholic Acid ; pharmacology

The present study was designed to evaluate the hepatoprotective and antioxidant potentials of silibinin (SBN) against N-nitrosodimethylamine (DMN)-induced toxic insults in the rat liver. The liver damage was induced in Wistar albino rats by repeated administration of DMN (10 mg·kg(-1) b.w., i.p.) on 3 consecutive days per week for 3 weeks. SBN (100 mg·kg(-1) b.w., p.o.) was given daily to the DMN treated rats for two weeks. The marker enzymes of liver toxicity and second-line enzymic and non-enzymic antioxidants were evaluated in serum and liver tissues before and after SBN treatment. Histopathology of the liver was evaluated by H & E staining. The DMN treatment produced a progressive increase in all the serum marker enzymes (AST, ALT, ALP, LDH, and γ-GT), peaking on Day 21. This treatment produced highly significant decreases in all the second-line antioxidant parameters (GSH, GST, GR, GPx, and vitamins C and E). The SBN treatment significantly reversed the DMN-induced damages, towards normalcy. Histopathological studies confirmed the development of liver toxicity in DMN-treated rats, which was reversed by SBN treatment in corroboration with the aforementioned biochemical results, indicating the hepatoprotective and antioxidant properties of SBN. In conclusion, the DMN-induced degenerative changes in the liver were alleviated by SBN treatment and this protective ability may be attributed to its antioxidant, free radical scavenging, and membrane stabilizing properties.
Animals ; Antioxidants ; pharmacology ; Chemical and Drug Induced Liver Injury ; drug therapy ; Dimethylnitrosamine ; toxicity ; Female ; Glutathione ; metabolism ; Male ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Silybin ; Silymarin ; pharmacology

The traditional medicinal herbs are natural product, and have no obviously toxic action and side effect, and their resources are extensive. The adverse effects produced by aldose reductase inhibitors in traditional medicinal herbs are less than those from chemical synthesis and micro-organism, they can effectively prevent and delay diabetic complication, such as diabetic nephropathy, vasculopathy, retinopathy, peripheral neuropathy, and so on. They will have a wonderful respect. Flavonoid compounds and their derivates from traditional medicinal herbs are active inhibitors to aldose reductase, such as quercetin, silymarin, puerarin, baicalim, berberine and so on. In addition, some compound preparations show more strongly activity in inhibiting aldose reductase and degrading sorbitol contents, such as Shendan in traditional medicinal herbs being active inhibitors and Jianyi capsule, Jinmaitong composita, Liuwei Di-huang pill, et al. The progresses definite functions of treating diabetes complications have been reviewed.
Aldehyde Reductase ; antagonists & inhibitors ; metabolism ; Animals ; Diabetic Nephropathies ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Enzyme Inhibitors ; metabolism ; Humans ; Isoflavones ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Quercetin ; isolation & purification ; pharmacology ; Silymarin ; isolation & purification ; pharmacology

OBJECTIVE: To determine the hepatoprotective effect of silymarin with Chang cell cultures. Specifically, to investigate the antioxidant properties of silymarin and its protective function in reducing pro-apoptotic markers. METHODS: Intracellular free radical levels were assessed with dichlorofluorescein (DCF) fluorescence after exposing cells to an oxidative stress of 400 μmol/L H2O2 for 20 min. Levels of cellular ATP and bax expression were examined to evaluate the protective effects of silymarin. RESULTS: Silymarin significantly reduced the DCF fluorescence signal. Cell viability, assessed by the MTT assay, showed that silymarin enhanced the cell growth. Drug treatment was also associated with enhanced ATP levels, and reduced Bax and protein mRNA levels. CONCLUSION Silymarin can function as a hepatoprotectant against free radical damage due to oxidative stress. The protective nature extends to reducing levels of pro-apoptotic Bax protein. Silymarin may be a useful adjuvant for the treatment of specific liver diseases.
Adenosine Triphosphate ; metabolism ; Antioxidants ; pharmacology ; Apoptosis ; drug effects ; Cell Line ; Fluoresceins ; Free Radicals ; metabolism ; Hepatocytes ; cytology ; metabolism ; Humans ; Hydrogen Peroxide ; Protective Agents ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Silymarin ; pharmacology ; bcl-2-Associated X Protein ; genetics ; metabolism

OBJECTIVETo observe the effects of silymarin on hepatic microsomal and mitochondrial membrane fluidity in mice.

METHODLiver microsomal and mitochondrial membranes were labled by ANS and DPH. Membrane fluorensent intensity (F), fluorensent polarization(P) and microviscosily(eta) of liver microsome and mitochondria were determined.

RESULTSil increased the external membrane fluidities of liver microsome and mitochondria, and decreased the internal membrane fluidities of liver microsome and mitochondria. Pretreatment with CCl4, the external membrane fluidity of liver microsome and mitochondria were increased, and the internal membrane fluidities of liver microsome and mitochondria were decreased. After given sil 140,280 mg.kg-1, the increased external membrane fluidities of liver microsome and mitochondria were lowered, and the decreased internal membrane fluidities of liver microsome and mitochondria were enhanced in a dose-dependent manner.

CONCLUSIONThe protective effects of sil on liver injury may be related to the recovery of the membrane fluidities of liver microsome and mitochondria.

Animals ; Carbon Tetrachloride Poisoning ; Liver Diseases ; etiology ; pathology ; Male ; Membrane Fluidity ; drug effects ; Mice ; Microsomes, Liver ; drug effects ; Milk Thistle ; chemistry ; Mitochondria, Liver ; drug effects ; Plants, Medicinal ; chemistry ; Protective Agents ; pharmacology ; Seeds ; chemistry ; Silymarin ; isolation & purification ; pharmacology

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Carbon Tetrachloride ; toxicity ; Chemical and Drug Induced Liver Injury ; drug therapy ; Female ; Liver ; drug effects ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Silymarin ; administration & dosage ; pharmacology ; therapeutic use

OBJECTIVEThe beneficial effects of silymarin have been extensively studied in the context of inflammation and cancer treatment, yet much less is known about its therapeutic effect on diabetes. The present study was aimed to investigate the cytoprotective activity of silymarin against diabetes-induced cardiomyocyte apoptosis.

METHODSRats were randomly divided into: control group, untreated diabetes group and diabetes group treated with silymarin (120 mg/kg•d) for 10 d. Rats were sacrificed, and the cardiac muscle specimens and blood samples were collected. The immunoreactivity of caspase-3 and Bcl-2 in the cardiomyocytes was measured. Total proteins, glucose, insulin, creatinine, AST, ALT, cholesterol, and triglycerides levels were estimated.

RESULTSUnlike the treated diabetes group, cardiomyocyte apoptosis increased in the untreated rats, as evidenced by enhanced caspase-3 and declined Bcl-2 activities. The levels of glucose, creatinine, AST, ALT, cholesterol, and triglycerides declined in the treated rats. The declined levels of insulin were enhanced again after treatment of diabetic rats with silymarin, reflecting a restoration of the pancreatic β-cells activity.

CONCLUSIONThe findings of this study are of great importance, which confirmed for the first time that treatment of diabetic subjects with silymarin may protect cardiomyocytes against apoptosis and promote survival-restoration of the pancreatic β-cells.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Glucose ; Cholesterol ; blood ; Creatinine ; blood ; Diabetes Mellitus, Experimental ; complications ; Diabetic Cardiomyopathies ; prevention & control ; Heart ; drug effects ; Immunohistochemistry ; Insulin ; blood ; Male ; Myocardium ; pathology ; Myocytes, Cardiac ; drug effects ; Rats ; Silymarin ; pharmacology ; Triglycerides ; blood

OBJECTIVETo investigate the protection of silymarin against the human mesenchymal stem cell (MSC) apoptosis induced by serum deprivation and its underlying mechanism.

METHODSHuman umbilical cord MSCs were cultured in the absence of serum, and the silymain of different concentration (1-10 µg/ml) was added into the medium. MTT test was performed to observe the cell proliferation status. After being cultured for 72 hours, the cells were collected, and flow cytometry with Annexin-V-PI double-staining was used to detect the apoptotic cells from the control and silymarin-treated groups. Furthermore, the intracellular contents of BAX and BCL-2 were detected by Western blot for exploring the potential mechanism.

RESULTSThe silymarin promoted the proliferation of human UC-MSCs in a dose-dependent manner, reaching its maximal at a dose of 5 µg/ml. Moreover, silymarin could inhibit the serum deprivation-induced apoptosis of MSCs and, the inhibitory rate reached up to 30% when it was added at a concentration of 5 µg/ml. The content of intracellular BAX was obviously elevated after serum-deprivation treatment, and this increase could be blunted by the addition of silymarin. Meanwhile, the content of BCL-2 was not obviously changed.

CONCLUSIONThe silymarin can stimulate MSC growth and inhibit the apoptosis of MSCs probably by the mitochondria pathway.

Apoptosis ; drug effects ; Cell Proliferation ; Culture Media, Serum-Free ; Humans ; Mesenchymal Stromal Cells ; drug effects ; Mitochondria ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Silymarin ; pharmacology ; Umbilical Cord ; cytology ; bcl-2-Associated X Protein ; metabolism

Silibinin, from milk thistle (Silybum marianum), is a flavonolignan with anti-oxidative and anti-inflammatory properties. It has been therapeutically used for the treatment of hepatic diseases in China, Germany and Japan. Recently, increasing evidences prove that silibinin is also a potent antitumor agent, and the major anti-tumor mechanism for silibinin is the prominent inhibition of the activities of receptor tyrosine kinases (RTKs) and their downstream signal molecules in a variety of tumor cell lines, such as epidermal growth factor receptor 1 (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) signaling pathways. Meanwhile, the evidences that silibinin selectively scavenges hydroxyl free radical (*OH) and specifically inhibits the action of nuclear factor kappaB (NF-kappaB) provide more complicated explanations for its antioxidant and anti-inflammatory effects. Some new findings such as that silibinin attenuating the cognitive deficits induced by amyloid beta protein (Abeta) peptide through its antioxidative and anti-inflammatory properties is valuable to broad the medical prospect of silibinin. In this review, we discuss the molecular pharmacological mechanisms of silibinin, focusing on its inhibition of tyrosine kinases, actions of antioxidation, free radical scavenging, immunoregulation and anti-inflammation.
Amyloid beta-Peptides ; metabolism ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Antioxidants ; pharmacology ; Enzyme Activation ; Free Radical Scavengers ; pharmacology ; Humans ; Milk Thistle ; chemistry ; Molecular Structure ; NF-kappa B ; metabolism ; Protein-Tyrosine Kinases ; metabolism ; Reactive Oxygen Species ; metabolism ; Receptor Protein-Tyrosine Kinases ; metabolism ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, IGF Type 1 ; metabolism ; Signal Transduction ; drug effects ; Silymarin ; chemistry ; isolation & purification ; pharmacology