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

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

OBJECTIVEThe purpose of the present study was to evaluate the nephroprotective and antioxidant properties of Triphala against bromobenzene-induced nephrotoxicity in female Wistar albino rats.

METHODSAnimals were divided into five groups of six rats and treated as follows: Group I was a normal control and received no treatment, Group II received only bromobenzene (10 mmol/kg), Groups III and IV received bromobenzene and Triphala (250 and 500 mg/kg, respectively), Group V received Triphala alone (500 mg/kg), and Group VI received bromobenzene and silymarin (100 mg/kg). Antioxidant status and serum kidney functional markers were analyzed.

RESULTSBromobenzene treatment resulted in significant (P< 0.05) decreases in the activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase as well as total reduced glutathione. There was a significant (P< 0.05) increase in lipid peroxidation in kidney tissue homogenates. There were significant (P< 0.05) reductions in the levels of serum total protein and albumin as well as significant (P< 0.05) increases in serum creatinine, urea and uric acid. The oral administration of two different doses (250 and 500 mg/kg) of Triphala in bromobenzene-treated rats normalized the tested parameters. The histopathological examinations of kidney sections of the experimental rats support the biochemical observations.

CONCLUSIONTriphala treatment alleviated the nephrotoxic effects of bromobenzene by increasing the activities of antioxidant enzymes and reducing the levels of lipid peroxidation and kidney functional markers.

Acute Kidney Injury ; chemically induced ; diagnosis ; metabolism ; prevention & control ; Animals ; Antioxidants ; pharmacology ; Bromobenzenes ; pharmacology ; Disease Models, Animal ; Female ; Kidney ; metabolism ; pathology ; Kidney Function Tests ; Medicine, Ayurvedic ; Phyllanthus emblica ; Plant Preparations ; chemistry ; pharmacology ; Plant Structures ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Silymarin ; pharmacology ; Terminalia ; Treatment Outcome

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

BACKGROUND/AIMS: Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. METHODS: Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. RESULTS: Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. CONCLUSIONS: Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.
Antineoplastic Agents/*pharmacology ; Carcinoma, Hepatocellular/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cell Survival/drug effects ; Down-Regulation/drug effects ; Drug Screening Assays, Antitumor ; Drug Synergism ; Humans ; Liver Neoplasms/metabolism/pathology ; Niacinamide/*analogs & derivatives/pharmacology ; Phenylurea Compounds/*pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Quinazolines/*pharmacology ; Receptor, Epidermal Growth Factor/metabolism ; Signal Transduction/drug effects ; Silymarin/*pharmacology

OBJECTIVE: To explore the eff ect of silibinin on β cells in C57BL/6J mice fed a high-fat diet and the possible mechanisms. METHODS: A total of 18 male C57BL/6J mice at 3 weeks old were divided into a normal chow group (n=6), a high-fat diet group (n=6) and a high-fat diet plus silibinin group (n=6). Aft er intervention for 10 weeks, fasting blood glucose (FBG), fasting insulin (FINS), triglycerides (TG), alanine aminotransferase (ALT), creatinine (Cr) and blood urea nitrogen (BUN), lipid metabolism, antioxidant enzyme activities and apoptosis were evaluated. Pancreatic tissues were isolated to examine insulin-induced gene-1 (Insig-1), sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthetase (FAS) mRNA and protein expression. RESULTS: Compared with the high-fat diet group, the function of insulin secretion was improved, and the level of blood glucose was decreased in the high-fat diet plus silibinin group (P<0.05). The levels of lipid content and oxidative stress and the rates of β cell apoptosis were lower in high-fat diet plus silibinin group than those in the high-fat diet group (both P<0.05). Simultaneously, the silibinin could promote the expression of Insig-1 and depress the expression of SREBP-1c and FAS (all P<0.05). Moreover, there was no significant difference in the levels of serum ALT, Cr and BUN among the 3 groups (all P>0.05). CONCLUSION Silibinin can protect β cells of mice fed a high-fat diet, and this effect might be related to, at least partially, increase in its antioxidative ability through regulation of insig-1/SREBP-1c pathway. Moreover, silibinin is safe for long-term treatment.
Alanine Transaminase ; blood ; Animals ; Apoptosis ; Blood Glucose ; analysis ; Blood Urea Nitrogen ; Creatinine ; blood ; Diet, High-Fat ; Fatty Acid Synthases ; metabolism ; Insulin ; blood ; Insulin-Secreting Cells ; cytology ; drug effects ; Lipid Metabolism ; Lipids ; Male ; Membrane Proteins ; metabolism ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Silybin ; Silymarin ; pharmacology ; Sterol Regulatory Element Binding Protein 1 ; metabolism ; Triglycerides ; blood

The present study was conducted to investigate the effect of silymarin on experimental liver toxication induced by Fumonisin B1 (FB1) in BALB/c mice. The mice were divided into six groups (n = 15). Group 1 served as the control. Group 2 was the silymarin control (100 mg/kg by gavage). Groups 3 and 4 were treated with FB1 (Group 3, 1.5 mg/kg FB1, intraperitoneally; and Group 4, 4.5 mg/kg FB1). Group 5 received FB1 (1.5 mg/kg) and silymarin (100 mg/kg), and Group 6 was given a higher dose of FB1 (4.5 mg/kg FB1) with silymarin (100 mg/kg). Silymarin treatment significantly decreased (p < 0.0001) the apoptotic rate. FB1 administration significantly increased (p < 0.0001) proliferating cell nuclear antigen and Ki-67 expression. Furthermore, FB1 elevated the levels of caspase-8 and tumor necrosis factor-alpha mediators while silymarin significantly reduced (p < 0.0001) the expression of these factors. Vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) expressions were significantly elevated in Group 4 (p < 0.0001). Silymarin administration alleviated increased VEGF and FGF-2 expression levels (p < 0.0001). In conclusion, silymarin ameliorated toxic liver damage caused by FB1 in BALB/c mice.
Animals ; Antioxidants/*pharmacology ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Female ; Fibroblast Growth Factor 2/genetics/metabolism ; Fumonisins/*toxicity ; Gene Expression Regulation/drug effects ; Hepatocytes/*drug effects ; Ki-67 Antigen/metabolism ; Liver/drug effects ; Mice ; Mice, Inbred BALB C ; Mycotoxins/*toxicity ; Neovascularization, Physiologic/drug effects ; Proliferating Cell Nuclear Antigen/metabolism ; Silymarin/*pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism

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

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