Milk Thistle Abstracts 2

Liver-protective action of silymarin therapy in chronic alcoholic liver diseases

The effects of silymarin (Legalon) therapy on liver function tests, serum procollagen III peptide level and liver histology were studied in 36 patients with chronic alcoholic liver disease in a six month double blind clinical trial. During silymarin treatment serum bilirubin, aspartate aminotransferase and alanin-aminotransferase values have been normalized, while gamma-glutamyl transferase activity and procollagen III peptid level decreased. The changes were significant, and there was a significant difference between post-treatment values of the two groups, as well. In the placebo group only gamma-glutamyl transferase values decreased significantly but to a lesser extent than that in the silymarin group. The histological alterations showed an improvement in the silymarin group, while remained unchanged in the placebo group. These results indicate that silymarin exerts hepatoprotective activity and is able to improve liver functions in alcoholic patients.

Feher J, Deak G, Muzes G, et al.

Liver-protective action of silymarin therapy in chronic alcoholic liver diseases.

Orv Hetil (HUNGARY) 130:2723-2727; 1989.

Title: [The action of silymarin on Galactosamine-induced hepatitis in the rat (author's transl)]

Author: Barbarino F; Suciu A; Cotutiu C; Ban A; Source: Wien Klin Wochenschr

Date of Pub: 1977 Feb 4

Issue: 3 Volume: 89 Pagination: 90-

Abstract: The hepatoprotective action of Silymarin was studied in 65 male Wistar rats, prior to and following D-galactosamine intoxication. There was a marked reduction in the histological and ultrastructural changes in the nucleolus, nuclear membrane, mitochondria, granular and agranular endoplasmic reticulum and lysosomes of the liver cell and also in the Kupffer stellate cells. The reduction in glycogen and RNA loss was determined biochemically. The activities of many enzymes were kept constant (oxidoreductases, NADH2 diaphorase, G-6-phosphatase, Mg++ and K+/Na+-dependent ATPases, acid phosphatases).

Abstract By: Author

Transliterated/Vernacular Title: Die Wirkung von Silymarin auf die experimentelle Galaktosamin-Hepatitis beider Ratte

Title: Selectivity of silymarin on the increase of the glutathione content

in different tissues of the rat.

Author: Valenzuela A; Aspillaga M; Vial S; Guerra R; Source: Planta Med

Date of Pub: 1989 Oct Issue: 5 Volume: 55 Pagination: 420-2

Abstract: Silymarin, a flavonoid extracted from the seeds of the milk thistle, Silybum marianum, increases the redox state and the total glutathione content of the liver, intestine, and stomach of the rat. The same treatment does not affect the levels of the tripeptides in the kidney, lung, and spleen. This selective effect of the flavonoid on the digestive organs is ascribed to its pharmacokinetics on the digestive track, where the biliary concentration of silymarin is increased and maintained via the entero-hepatic circulation.

Abstract By: Author

Title: Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Author: Dehmlow C; Erhard J; de

Groot H; Source: Hepatology

Date of Pub: 1996 Apr Issue: 4 Volume: 23 Pagination: 749-54

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.

Abstract By: Author

Address: Institut fÍur Physiologische Chemie, UniversitÍatsklinikum, Essen, Germany.

Title: Effect of silymarin on experimental liver lesions.

Author: Barbarino F; Neumann E; Deaciuc I; Ghelberg NW; Suciu A; Cotuçtiu C; Racoviçt&abreve L; Stroil&abreve C; Nagy S; P&abrever&abreveu N; Toader S; Brilinschi C;

Source: Med Interne

Date of Pub: 1981 Oct-Dec Issue: 4 Volume: 19 Pagination: 347-57

Abstract: The effect of Silymarin (Legalon) upon liver lesions was investigated using four experimental models: In acute galactosamine-hepatitis, Silymarin administration achieved protection of the liver structure (electron-microscopy included), liver cell glycogen, RNA and enzymatic activity, Galactosamine-depressed gluconeogenesis in the isolated perfused rat liver was significantly preserved by Silymarin treatment. In lead and cadmium poisoning the structural damage and histochemical and histoenzymatic changes were partly but significantly prevented. The complex noxious effects of Imuran overdoses were favourably influenced by Silymarin, without diminishing the cytostatic-immunosuppressive action of Imuran.

Abstract By: Author

Title [Stimulation of RNA synthesis in rat liver and isolated hepatocytes by silybin, an antihepatotoxic agent from Silybum marianum L. Gaertn (author's transl)]

Original Title

Stimulierung der RNA-Synthese in Rattenleber und in isolierten Hepatozyten durch Silybin, einen antihepatotoxischen Wirkstoff aus Silybum marianum L. Gaertn

Author Sonnenbichler J; Mattersberger J; Rosen H

Source Hoppe Seylers Z Physiol Chem, 357: 8, 1976 Aug, 1171-80

Abstract

The incorporation of [3H] orotic acid into RNA from rat livers is stimulated by the flavonolignane derivative Silybin. The time course of the RNA synthesis and its dose dependence were demonstrated with isolated hepatocytes and [3H]uridine. The specific radioactivity of the newly synthesized RNA in rats treated with silybin is markedly higher than that of the controls. From preliminary experiments there is no indication that the synthesis of a distinct species of RNA is stimulated preferentially.

Language of Publication

German

Unique Identifier

77027528

Drug-membrane interactions: silymarin, silibyn and microsomal membranes.

Author Parasassi T; Martellucci A; Conti F; Messina B

Source Cell Biochem Funct, 2: 2, 1984 Apr, 85-8

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.

Language of Publication

English

Unique Identifier

84283120

Protection against microcystin-LR-induced hepatotoxicity by Silymarin: biochemistry, histopathology, and lethality.

Author

Mereish KA; Bunner DL; Ragland DR; Creasia DA

Address

Medical Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011.

Source

Pharm Res, 8: 2, 1991 Feb, 273-7

Abstract

Microcystin-LR, a cyclic heptapeptide synthesized by the blue-green algae, Microcystis aeruginosa, is a potent hepatotoxin. Pathological examination of livers from mice and rats that received microcystin-LR revealed severe, peracute, diffuse, centrilobular hepatocellular necrosis, and hemorrhage. These changes were correlated with increased serum activities of sorbitol dehydrogenase, alanine aminotransferase, and lactate dehydrogenase. Pretreatment of either rats or mice with a single dose of silymarin, a flavonolignane isolated from the wild artichoke (Silybum marianum L. Gaertn), completely abolished the lethal effects, pathological changes, and significantly decreased the levels of serum enzymes induced by microcystin-LR intoxication.

Language of Publication

English

Unique Identifier

91219343

Advances in pharmacological studies of silymarin.

Author

Rui YC

Address

College of Pharmacy, Second Military Medical University, Shanghai, China.

Source

Mem Inst Oswaldo Cruz, 86 Suppl 2:1991, 79-85

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. 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)

Language of Publication

English

Unique Identifier

93062091

Silymarin in liver diseases. Pratical inhibition of fibrosis

Original Title

SILYMARIN BEI HEPATOPATHIEN. FIBROSE-HEMMUNG UNTER PRAXIS BEDINGEN

Author

Held C.

Address

Univ.klinik fur Innere Medizin, Schumannstrasse 20/21, 1040 Berlin, Germany

Source

THERAPIEWOCHE, 42/27-28 (1696-1701):1992

Abstract

Abstract not available online.

Language of Publication

German

Unique Identifier

92227439

Therapy of toxic hepatopathies: Mary's thistle extract lowers the fibrosis activity

Original Title

THERAPIE DER TOXISCHEN HEPATOPATHIEN. MARIENDISTEL VERRINGERT FIBROSEAKTIVITAT

Author

Held C.

Address

Universitatsklinikum Charite, Medizinische Fakultat, Humboldt-Universitat, Schumannstrasse 20/21, 10098Berlin, Germany

Source

THERAPIEWOCHE, 43/39 (2002-2009):1993

Abstract

Abstract not available online.

Language of Publication

German

Unique Identifier

93296206

Role of free-radical reactions in liver diseases

Author

Feher J.; Vereckei A.; Lengyel G.

Address

2nd Department of Medicine, Semmelweis University of Medicine, Szentkiralyi u. 46, 1088 Budapest, Hungary

Source

ACTA PHYSIOL. HUNG., 80/1-4 (351-361):1992

Abstract

Role of free-radical reactions is most significant in toxic liver injuries. Two traditional groups of liver injuries induced by drugs and chemicals are distinguished, 1. direct toxic type and 2. Idiosyncratic type. Liver injury of direct toxic type is generally developed following toxin exposure, it is dose dependent, incubation period is short, and the injury often affects other organs (e.g. kidney). Direct toxins frequently cause typical zonal necrosis usually without concomitant signs of hypersensitivity. It is typical of idiosyncratic reaction that it appears only in a shorter period of exposure, it cannot be predicted, it is not dose-dependent, its incubation period varies and sometimes (in one-fourth of cases) it is accompanied by extrahepatic symptoms of hypersensitivity (fever, leukocytosis, eosinophilia, rashes), its morphologic picture shows great variety. A part of direct toxins is toxic itself, in the other part the basic compound is not toxic but it changes into toxic metabolites in the liver. Liver is well-protected against free-radicals developing in the organism; it is one of our best antioxidant supplied organs. It is probably due to the one of the important tasks of liver, namely detoxication of drugs, chemicals and toxic materials, with subsequent release of free-radicals. It is proved by the fact that in normal bile peroxidized lipids produced by free-radical chain reactions can also be detected. The pathologic free-radical reactions and one of their sequelae, peroxidation of lipids (LPO) do not necessarily cause cell and tissue damage. Antioxidant protection of cells and tissues is able to prevent free-radical injury and it enables, that the already developed damages become reversible. According to recent investigations, the lipid peroxidation, caused by free-radical reactions, or covalent binding of radical products to biomolecules does not lead directly to cellular destruction, only via further reactions. Such intermediary steps can be the phospholipase A2 activation, accumulation of lysophosphatides, poly-ADP- ribose polymerase repair enzyme activation, following oxidative damage of DNA, with subsequent NAD and ATP depletion. Its significance may be that the irreversible cellular and tissue damage can be prevented perhaps not only by administration of antioxidants, but also by compounds (e.g. phospholipase A2 inhibitors) affecting the above-mentioned biochemical mechanisms.

Language of Publication

English

Unique Identifier

94085702

Silybin inhibition of human T-lymphocyte activation.

Author

Meroni PL; Barcellini W; Borghi MO; Vismara A; Ferraro G; Ciani D;

Zanussi C

Address

Institute of Internal Medicine, Infectious Diseases and

Immunopathology, University of Milan, Italy.

Source

Int J Tissue React, 10: 3, 1988, 177-81

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.

Language of Publication

English

Unique Identifier

89138896 )

Silibinin (Legalon-70) enhances the motility of human neutrophils

immobilized by formyl-tripeptide, calcium ionophore, lymphokine and by

normal human serum.

Author

Kalmár L; Kádár J; Somogyi A; Gergely P; Csomós G; Fehér J

Address

Second Department of Medicine, Semmelweis University, Budapest,

Hungary.

Source

Agents Actions, 29: 3-4, 1990 Mar, 239-46

Abstract

Experiments reported here were designed to investigate the effect of

silibinin (extracted from Silybum marianum) on human polymorphonuclear

leukocyte (PMN) motility and on leukocyte immobilizing activity of

lymphokine (leukocyte inhibitory factor, LIF), formyl-Met-Leu-Phe

(fMLP), calcium ionophore A-23187 and human sera inactivated by heat

(HI-S). In the in vitro experiments, silibinin (1-10 micrograms/ml)

failed to influence the random motility of unstimulated PMNS in agarose

droplet assay, but enhanced the motility of the PMNs immobilized by

fMLP, calcium ionophore, LIF or by autologous human sera. In the in

vivo study, silibinin (Legalon-70) two hours after the administration

was effective in enhancing spontaneous motility of leukocytes obtained

from health volunteers which action could be regarded as a consequence

of the decrease of leukocyte immobilizing activity being present in

normal human plasma.

Language of Publication

English

Unique Identifier

90252677

Gastroprotection induced by silymarin, the hepatoprotective principle

of Silybum marianum in ischemia-reperfusion mucosal injury: role of

neutrophils.

Author

Alarcón de la Lastra AC; Martín MJ; Motilva V; Jiménez M; La Casa C;

López A

Address

Departamento de Farmacia y Tecnología Farmacéutica, Facultad de

Farmacia, Sevilla, Spain.

Source

Planta Med, 61: 2, 1995 Apr, 116-9

Abstract

Investigations were carried out to determine the antiulcer effects of

silymarin, the hepatoprotective principle of Silybum marianum L.

Gaertn., in gastric injury induced by ischemia-reperfusion and its

effects on mucosal myeloperoxidase activity, an index of

polymorphonuclear leukocyte infiltration, after injury in rats. These

results were compared with those from rats that received allopurinol,

an inhibitor of xanthine oxidase and with those from rats made

neutropenic by prior administration of dexamethasone and methotrexate.

Pretreatment with silymarin prevented post-ischemic mucosal injury. The

mean ulcer indexes (U.I.) of rats treated with 25, 50 mg, and 100 mg

silymarin/kg body weight (4.79 +/- 0.75, 4.50 +/- 0.81, and 3.63 +/-

0.74, respectively) were significantly lower (p < 0.05, 0.05, and p <

0.005) than that of control rats. Allopurinol was considerably more

potent in reducing the U.I. than silymarin, with a calculated U.I. of

2.33 +/- 0.45, p < 0.001. These protective effects were specifically

related to a reduction in the number of neutrophils in the gastric

mucosa. Reduction in the numbers of circulating neutrophils by treating

rats with methotrexate (MPO level of 7.2 x 10(-2) +/- 0.56 x 10(-2)U/mg

wt) and dexamethasone (MPO level of 6.97 x 10(-2) +/- 0.68 x 10(-2)U/mg

wt) also resulted in a significant reduction in the susceptibility to

gastric damage induced by ischemia-reperfusion. These results suggest

that neutrophils play an important role in the gastric mucosal

dysfunction associated with ischemia-reperfusion. These findings also

indicate that the inhibitory effects of silymarin on neutrophil

function may contribute significantly to its gastroprotective actions.

Language of Publication

English

Unique Identifier

95273483

Immunomodulator effect of silymarin therapy in chronic alcoholic liver diseases

The effects of the hepatoprotective, antioxidant drug silymarin (Legalon)

on some cellular immune parameters of patients with histologically proven

chronic alcoholic liver disease were studied in a six month double blind

study. The lectin induced proliferative activity of the lymphocytes got

enhanced, the originally low T cell percentage and the originally high CD8+

cell percentage have been normalized, the antibody-dependent and natural

cytotoxicity of the lymphocytes decreased during silymarin therapy. All

these changes were significant, while in the placebo group no significant

changes occurred, except for a moderate elevation of the T cell percentage.

Thus, the immunomodulatory activity of silymarin might be involved in the

hepatoprotective action of the drug and improves the depressed

immunoreactivity of the patients.Deak G, Muzes G, Lang I, et al.

Immunomodulator effect of silymarin therapy in chronic alcoholic liver

diseases. Orv Hetil (HUNGARY) 131:1291-1292;1990.

HepC BC