Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity.
von Schönfeld J, Weisbrod B, Müller MK
Cell Mol Life Sci 1997 Dec 53:917-20
Cell Mol Life Sci • Volume 53 • Issue 11-12
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Abstract
Silymarin can be extracted from the milk thistle, and silibinin is the main component of the plant extract. Possibly due to their antioxidant and membrane-stabilizing properties, the compounds have been shown to protect different organs and cells against a number of insults. Thus liver, kidney, erythrocytes and platelets have been protected from the toxic effects of ethanol, carbon tetrachloride, cold ischemia and drugs, respectively. The effect of silibinin on endocrine and exocrine pancreas, however, has not been studied. We therefore investigated whether silibinin treatment attenuates cyclosporin A (CiA) toxicity on rat endocrine and exocrine pancreas. Groups of 15 male Wistar rats were treated for 8 days with CiA and/or silibinin. On day 9, endocrine and exocrine pancreatic functions were tested in vitro. At the end of the treatment period, blood glucose levels in vivo were significantly higher in rats treated with CiA while silibinin did not affect glucose levels. In vitro, insulin secretion was inhibited after treatment with silibinin, but amylase secretion was not affected. After treatment with CiA both insulin and amylase secretion were reduced. Silibinin and CiA had an additive inhibitory effect on insulin secretion, but silibinin attenuated CiA-induced inhibition of amylase secretion. Despite CiA treatment, amylase secretion was in fact restored to normal with the highest dose of silibinin. Thus silibinin inhibits glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo. This combination of effects could be useful in the treatment of non-insulin-dependent diabetes mellitus. Furthermore, silibinin protects the exocrine pancreas from CiA toxicity. As this inhibitory effect is probably unspecific, silibinin may also protect the exocrine pancreas against other insult principles, such as alcohol.
Silybin inhibition of human T-lymphocyte activation.
Meroni PL, Barcellini W, Borghi MO, Vismara A, Ferraro G, Ciani D, Zanussi C
Int J Tissue React 1988 10:177-81
Int J Tissue React • Volume 10 • Issue 3
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Abstract
Silybin, a 3-oxyflavone occurring in the thistle Silybum marianum, displays a dose-dependent inhibition of in-vitro lymphocyte blastogenesis induced by lectins (phytohaemagglutinin, Concanavalin A and pokeweed) and by anti-CD3 monoclonal antibody. The drug has no effect on cell viability and spontaneous 3H-thymidine incorporation, suggesting that the inhibitory activity is not due to aspecific toxicity. Since all the T-cell responses investigated require cell-membrane-associated events, the effect of silybin is probably at the level of the cell membrane, as for other flavonoids. Addition of CuSO4 prevents the inhibitory activity of silybin on PHA-induced proliferative response, indicating that the drug could exert its activity also by virtue of a chelation mechanism.
Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin.
Dehmlow C, Erhard J, de Groot H
Hepatology 1996 Apr 23:749-54
Hepatology • Volume 23 • Issue 4
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Abstract
The flavonoid silibinin, the main compound extracted from the milk thistle Silybum marianum, displays hepatoprotective properties in acute and chronic liver injury. To further elucidate the mechanisms by which it acts, we studied the effects of silibinin on different functions of isolated rat Kupffer cells, namely the formation of superoxide anion radical (02-), nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E(2) (PGE(2)), and leukotriene B(4) (LTB(4)). Production of 02- and NO were inhibited in a dose-dependent manner, with an 50 percent inhibitory concentration (IC(50)) value around 80 micro mol/L. No effect on TNF-alpha formation was detected. Opposite effects were found on the cyclooxygenase and 5-lipoxygenase pathway of arachidonic acid metabolism. Whereas no influence on PGE(2) formation was observed with silibinin concentrations up to 100 micro mol/L, a strong inhibitory effect on LTB(4) formation became evident. The IC(50)-value for inhibiting the formation of this eicosanoid was determined to be 15 micro mol/L silibinin. The strong inhibition of LTB(4), formation by silibinin was confirmed in experiments with phagocytic cells isolated from human liver. Hence, while rather high concentrations of silibinin are necessary to diminish free radical formation by activated Kupffer cells, significant inhibition of the 5-lipoxygenase pathway already occurs at silibinin concentrations which are achieved in vivo. Selective inhibition of leukotriene formation by Kupffer cells can at least partly account for the hepatoprotective properties of silibinin.
[Effects of bioflavonoids on the toxicity of T-toxin in rats. A morphological study]
Pozdniakov AL, Kravchenko LV, Avren'eva LI, Kazenkina NB
Vopr Pitan 2000 69:24-7
Vopr Pitan • Volume 69 • Issue 5
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Abstract
Subacute toxicity of T-2 toxin in rats was characterized by a primary defeat of liver, thymus, spleen and intraorgan arteries. In 75% of animals found out increase of the size and adipose infiltration of a liver, in all animals--reduction of the size of thymus (sharp) and spleen (moderate) and pronounced hypoplasia of lymphoid tissue. In the majority of rats vacuolation of cytoplasma of smooth-muscular walls of coronary and intrarenal arteries was revealed. In animals received T-2 toxin against a background of a diet with addition a flour from seeds of milk thistle with high contents of flavonoids, described morphological changes were expressed to a lesser degree and were observed less often. Moderate periportal adipose infiltration of a liver was revealed in 30% of animals, occupancy by cells of lymphoid tissue increased, the quantity and sizes of vacuoles in walls of vessels decreased.
[Effects of bioflavonoids on the toxicity of T-toxin in rats. A biochemical study]
Kravchenko LV, Avren'eva LI, Tutel'ian VA
Vopr Pitan 2000 69:20-3
Vopr Pitan • Volume 69 • Issue 5
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Abstract
The enrichment of a diet of rats by flavonoids of milk thistle, Silybum marianum, reduced toxicity of T-2 toxin and was accompanied by reduction of a degree of change of total and nonsedimentable activity of lysosomal enzymes and microsomal xenobiotic metabolizing enzymes.
Putative effect of silymarin on sawfly (Arge pullata)-induced hepatotoxicosis in sheep.
Thamsborg SM, Jørgensen , Brummerstedt E, Bjerregard J
Vet Hum Toxicol 1996 Apr 38:89-91
Vet Hum Toxicol • Volume 38 • Issue 2
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Abstract
The prevention of hepatotoxicity from sawfly larvae (Arge pullata) was studied in 8 lambs by using silymarin, a botanical compound isolated from Silybum marianum. Of 2 lambs dosed orally with larvae only, 1 had a marked toxic response whereas the other responded poorly as judged from clinical parameters, blood biochemistry and pathology. Two lambs treated with penicillin, glucose and silymarin 7 and 24 h after larvae dosing were not affected by toxicosis, whereas 2 lambs treated similarly but without silymarin responded intermediate to the other 2 groups. Our study suggests a favorable effect using silymarin in treatment of sawfly larvae-induced ruminant hepatotoxicosis.
Picroliv affords protection against thioacetamide-induced hepatic damage in rats.
Dwivedi Y, Rastogi R, Sharma SK, Garg NK, Dhawan BN
Planta Med 1991 Feb 57:25-8
Planta Med • Volume 57 • Issue 1
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Abstract
Thioacetamide (100 mg/kg), when administered to normal rats, caused a significant increase in the activities of 5'-nucleotidase and gamma-glutamyl transpeptidase and a decrease in the activities of glucose 6-phosphatase and succinate dehydrogenase enzymes in the liver. DNA, RNA, and proteins were increased while the cytochrome P450 in the microsomal fraction and the glycogen content in the liver were decreased significantly. Elevations in the activities of GOT, GPT, and alkaline phosphatase and bilirubin content in serum were also observed. Picroliv, a standardised glycoside fraction of Picrorhiza kurroa, in doses of 12.5 and 25 mg/kg prevented most of the biochemical changes induced by thioacetamide in liver and serum. The hepatoprotective activity of Picroliv was comparable with that of silymarin, a known hepatoprotective agent obtained from seeds of Silybum marianum.
Hepatoprotective activity of silymarin against hepatic damage in Mastomys natalensis infected with Plasmodium berghei.
Chander R, Kapoor NK, Dhawan BN
Indian J Med Res 1989 Dec 90:472-7
Indian J Med Res • Volume 90
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Abstract
Silymarin, a flavolignan from the seeds of Silybum marianum, showed significant hepatoprotective activity in P. berghei-induced hepatic damage in M. natalensis, as assessed by changes in several serum and liver biochemical parameters. Changes in lipoprotein-X, GOT, GPT, alkaline phosphatase and bilirubin were found to be protected by silymarin at different doses. Maximum activity was observed at a dose of 5 mg/kg bw, po. Silymarin had no effect on parasitaemia.
Drug-membrane interactions: silymarin, silibyn and microsomal membranes.
Parasassi T, Martellucci A, Conti F, Messina B
Cell Biochem Funct 1984 Apr 2:85-8
Cell Biochem Funct • Volume 2 • Issue 2
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Abstract
Silymarin and silibyn are extracted from the seeds of Silybum marianum and used as a liver protectant because of their free radical scavenging. When incorporated into rabbit liver microsomes they cause a small decrease in the flourescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) but not of 1-anilinononaphthalene-8-sulphonic acid (ANS), incorporated into the membranes. They do, however, reduce the fluorescence intensity of incorporated ANS without changing the wavelength of maximum intensity. These observations suggest that the drugs are incorporated into the hydrophobic-hydrophilic interface of the microsomal bilayer and perturb the structure by influencing the packing of the acyl chains.
The influence of silybin from Silybum marianum (L.) Gaertn. on in vitro phosphatidyl choline biosynthesis in rat livers.
Schriewer H, Weinhold F
Arzneimittelforschung 1979 29:791-2
Arzneimittelforschung • Volume 29 • Issue 5
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Abstract
In rat livers, removed 60 min after i.p. application of 150.6 mg/kg silybin-dihemisuccinate-di-Na-salt, in vitro incorporation of choline-(methyl-14C) into phosphatidyl choline by the postmitochondrial fraction of liver homogenates was enhanced in comparison with controls. These results are associated with increased activities of CTP-choline-phosphate cytidyltransferase. Enzyme activities were also enhanced after addition of 7.5 x 10(-6) mol/l silybin to incubation mixtures obtained from untreated rats.
Advances in pharmacological studies of silymarin.
Rui YC
Mem Inst Oswaldo Cruz 1991 86 Suppl 2:79-85
Mem Inst Oswaldo Cruz • Volume 86 Suppl 2
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Abstract
Silymarin is the flavonoids extracted from the seeds of Silybum marianum (L) Gearth as a mixture of three structural isomers: silybin, silydianin and silychristin, the former being the most active component. Silymarin protects liver cell membrane against hepatotoxic agents and improves liver function in experimental animals and humans. It is generally accepted that silymarin exerts a membrane-stabilizing action preventing or inhibiting membrane peroxidation. The experiments with soybean lipoxygenase showed that the three components of silymarin brought about a concentration-dependent non-competitive inhibition of the lipoxygenase. The experiments also showed an analogous interaction with animal lipoxygenase, thus showing that an inhibition of the peroxidation of the fatty acid in vivo was self-evident. Silybin almost completely suppressed the formation of PG at the highest concentration (0.3 mM) and proved to be an inhibitor of PG synthesis in vitro. In our experiments, silybin at lower dose (65 mg/kg) decreased liver lipoperoxide content and microsomal lipoperoxidation to 84.6% and 68.55% of those of the scalded control rats respectively, and prevented the decrease of liver microsomal cytochrome p-450 content and p-nitroanisole-O-demethylase activity 24 h post-scalding. Effects of silymarin on cardiovascular system have been studied in this university since 1980. P. O silymarin 800 mg/kg/d or silybin 600 mg/kg/d reduced plasma total cholesterol, LDL-C and VLDL-C. They however, enhanced HDL-C in hyperlipemic rats.<Whats this? Any fellow steroid users watch their cholesterol?> Further studies showed that silymarin enhanced HDL-C but didn't affect HDL-C, a property of this component which is beneficial to treatment of atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Silymarin as a potential hypocholesterolaemic drug.
Skottová N, Krecman V
Physiol Res 1998 47:1-7
Physiol Res • Volume 47 • Issue 1
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Abstract
Silymarin, a mixture of flavonolignans from medicinal plant Silybum marianum, is used in supportive treatment of liver diseases of different etiology due to its hepatoprotective activity, which is considered to involve antioxidative and the membrane stabilizing effects. The liver plays an important role in regulation of metabolism of plasma lipoproteins, and liver injury is often reflected as a secondary dyslipoproteinaemia, which may lead to the development of atherosclerosis, particularly when associated with hypercholesterolaemia. This review summarizes the experimental evidence indicating that silymarin-induced protection of liver functions may be of benefit with regard to liver lipid metabolism related to the regulation of plasma lipoproteins. Moreover, some data suggest that silymarin could have a direct effect on liver cholesterol metabolism by inhibiting cholesterol biosynthesis. It is proposed that silymarin deserves to be studied as a potential hypocholesterolaemic agent.
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