€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****HEPATOLOGY***** Dehmlow C Erhard J de Groot H Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. In: Hepatology (1996 Apr) 23(4):749-54 ISSN: 0270-9139 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. Registry Numbers: 10102-43-9 (Nitric Oxide) 11062-77-4 (Superoxides) 22888-70-6 (Silymarin) 363-24-6 (Dinoprostone) 71160-24-2 (Leukotriene B4) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AGENTS AND ACTIONS***** Kalmar L Kadar J Somogyi A Gergely P Csomos G Feher J Silibinin (Legalon-70) enhances the motility of human neutrophils immobilized by formyl-tripeptide, calcium ionophore, lymphokine and by normal human serum. In: Agents Actions (1990 Mar) 29(3-4):239-46 ISSN: 0065-4299 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. Registry Numbers: EC 1.15.1.1 (Superoxide Dismutase) 22888-70-6 (Silymarin) 52665-69-7 (Calcimycin) 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARZNEIMITTEL-FORSCHUNG***** Schriewer H Weinhold F The influence of silybin from Silybum marianum (L.) Gaertn. on in vitro phosphatidyl choline biosynthesis in rat livers. In: Arzneimittelforschung (1979) 29(5):791-2 ISSN: 0004-4172 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CELL BIOCHEMISTRY AND FUNCTION***** Parasassi T Martellucci A Conti F Messina B Drug-membrane interactions: silymarin, silibyn and microsomal membranes. In: Cell Biochem Funct (1984 Apr) 2(2):85-8 ISSN: 0263-6484 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. Registry Numbers: 1720-32-7 (Diphenylhexatriene) 22888-70-6 (Silymarin) 82-76-8 (1-anilino-8-naphthalenesulfonate) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****HOPPE-SEYLERS ZEITSCHRIFT FUR PHYSIOLOGISCHE CHEMIE***** Sonnenbichler J Mattersberger J Rosen H [Stimulation of RNA synthesis in rat liver and isolated hepatocytes by silybin, an antihepatotoxic agent from Silybum marianum L. Gaertn (author's transl)] Stimulierung der RNA-Synthese in Rattenleber und in isolierten Hepatozyten durch Silybin, einen antihepatotoxischen Wirkstoff aus Silybum marianum L. Gaertn In: Hoppe Seylers Z Physiol Chem (1976 Aug) 357(8):1171-80 ISSN: 0018-4888 (Published in German) 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INDIAN JOURNAL OF MEDICAL RESEARCH***** Chander R Kapoor NK Dhawan BN Hepatoprotective activity of silymarin against hepatic damage in Mastomys natalensis infected with Plasmodium berghei. In: Indian J Med Res (1989 Dec) 90:472-7 ISSN: 0019-5340 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. Registry Numbers: 22888-70-6 (Silymarin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INTERNATIONAL JOURNAL OF TISSUE REACTIONS***** Meroni PL Barcellini W Borghi MO Vismara A Ferraro G Ciani D Zanussi C Silybin inhibition of human T-lymphocyte activation. In: Int J Tissue React (1988) 10(3):177-81 ISSN: 0250-0868 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. Registry Numbers: 22888-70-6 (Silymarin) 50-89-5 (Thymidine) 7440-50-8 (Copper) 9007-49-2 (DNA) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF HEPATOLOGY***** Ferenci P Dragosics B Dittrich H Frank H Benda L Lochs H Meryn S Base W Schneider B Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. In: J Hepatol (1989 Jul) 9(1):105-13 ISSN: 0168-8278 Silymarin, the active principle of the milk thistle Silybum marianum, protects experimental animals against various hepatotoxic substances. To determine the effect of silymarin on the outcome of patients with cirrhosis, a double blind, prospective, randomized study was performed in 170 patients with cirrhosis. 87 patients (alcoholic 46, non-alcoholic 41; 61 male, 26 female; Child A, 47; B, 37; C, 3; mean age 57) received 140 mg silymarin three times daily. 83 patients (alcoholic 45, non-alcoholic 38; 62 male, 21 female; Child A, 42; B, 32; C, 9: mean age 58) received a placebo. Non-compliant patients and patients who failed to come to a control were considered as 'drop outs' and were withdrawn from the study. All patients received the same treatment until the last patient entered had finished 2-years of treatment. The mean observation period was 41 months. There were 10 drop outs in the placebo group and 14 in the treatment group. In the placebo group, 37 (+2 drop outs) patients had died, and in 31 of these, death was related to liver disease. In the treatment group, 24 (+4 drop outs) had died, and in 18 of these, death was related to liver disease. The 4-year survival rate was 58 +/- 9% (S.E.) in silymarin-treated patients and 39 +/- 9% in the placebo group (P = 0.036). Analysis of subgroups indicated that treatment was effective in patients with alcoholic cirrhosis (P = 0.01) and in patients initially rated 'Child A' (P = 0.03). No side effects of drug treatment were observed.(ABSTRACT TRUNCATED AT 250 WORDS) Registry Numbers: 22888-70-6 (Silymarin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MEMORIAS DO INSTITUTO OSWALDO CRUZ***** Rui YC Advances in pharmacological studies of silymarin. In: Mem Inst Oswaldo Cruz (1991) 86 Suppl 2:79-85 ISSN: 0074-0276 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) Registry Numbers: 22888-70-6 (Silymarin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMACEUTICAL RESEARCH***** Mereish KA Bunner DL Ragland DR Creasia DA Protection against microcystin-LR-induced hepatotoxicity by Silymarin: biochemistry, histopathology, and lethality. In: Pharm Res (1991 Feb) 8(2):273-7 ISSN: 0724-8741 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. Registry Numbers: 101043-37-2 (cyanoginosin LR) 22888-70-6 (Silymarin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMACOLOGICAL RESEARCH***** Bosisio E Benelli C Pirola O Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. In: Pharmacol Res (1992 Feb-Mar) 25(2):147-54 ISSN: 1043-6618 The effect of several flavanolignans (silicristin, silidianin, silybin and isosilybin) present in silymarin, the extract of Silybum marianum fruits, was tested on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. In microsomes lipid peroxidation was generated by ADP/Fe2+ and NADPH. All flavanolignans inhibited peroxidation in a concentration dependent manner. In hepatocytes lipid peroxidation was induced by ADP/Fe3+ complex and cell damage was evaluated as LDH activity released in the medium. The inhibition of the peroxidative process by flavanolignans was also evident in this model, even if with a potency order different from that found in microsomes. In contrast, the effect on LDH release was significant only for silybin and isosilybin, the other compounds being inactive on this parameter. Registry Numbers: EC 1.1.1.27 (Lactate Dehydrogenase) 22888-70-6 (Silymarin) 29782-68-1 (silydianin) 33889-69-9 (silychristin) 72581-71-6 (isosilybin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANTA MEDICA***** Valenzuela A Aspillaga M Vial S Guerra R Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. In: Planta Med (1989 Oct) 55(5):420-2 ISSN: 0032-0943 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. Registry Numbers: 22888-70-6 (Silymarin) 70-18-8 (Glutathione) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Wong SM Wong MM Seligmann O Wagner H New antihepatotoxic naphtho-pyrone glycosides from the seeds of Cassia tora. In: Planta Med (1989 Jun) 55(3):276-80 ISSN: 0032-0943 Two new naphtho-pyrone glycosides, 9-[(beta-D-glucopyranosyl-(1----6)- O-beta-D-glucopyranosyl)oxy]-10- hydroxy-7-methoxy-3-methyl-1H- naphtho[2,3-c]pyran-1 -one (5) and 6-[(alpha-apiofuranosyl-(1----6)-O- beta-D-glucopyranosyl)oxy]- rubrofusarin (6), together with cassiaside (3) and rubrofusarin-6-beta-gentiobioside (4) were isolated from the seeds of Cassia tora L. Their structures were elucidated on the basis of chemical and spectral data. The naphtho- gamma-pyrone glycosides (3, 4, and 6) were found to have significant hepato-protective effects against galactosamine damage, which were higher than that of silybin from Silybum marianum. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Alarcon de la Lastra AC Martin MJ Motilva V Jimenez M La Casa C Lopez A Gastroprotection induced by silymarin, the hepatoprotective principle of Silybum marianum in ischemia-reperfusion mucosal injury: role of neutrophils. In: Planta Med (1995 Apr) 61(2):116-9 ISSN: 0032-0943 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. Registry Numbers: EC 1.11.1.7 (Peroxidase) 22888-70-6 (Silymarin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Dwivedi Y Rastogi R Sharma SK Garg NK Dhawan BN Picroliv affords protection against thioacetamide-induced hepatic damage in rats. In: Planta Med (1991 Feb) 57(1):25-8 ISSN: 0032-0943 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. Registry Numbers: 121-34-6 (Vanillic Acid) 12708-05-3 (kutkin) 22888-70-6 (Silymarin) 62-55-5 (Thioacetamide) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****STEP PERSPECTIVE***** Hernandez V Liver function and HIV-1 infection. In: STEP Perspect (1995 Summer) 7(2):13-5 Persons with HIV may have previous or concurrent liver impairment as a result of injection drug use, hepatitis, alcohol abuse, and damage from medications. Additional stress is placed on the liver by low- grade opportunistic infections and hemophilia. It is especially important that persons with HIV care for their liver to help this organ remain physiologically normal during chronic and acute management of HIV infection. Although modern pharmaceutical medicine does not provide liver tonics or supportives, herbal medicines have been used to ease liver stress for ages. Readily available liver protectants and their actual mechanism of action, including thioctic acid, glycyrrhizin, and Silybum marianum, are described. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****VETERINARY AND HUMAN TOXICOLOGY***** Thamsborg SM Jorgensen Brummerstedt E Bjerregard J Putative effect of silymarin on sawfly (Arge pullata)-induced hepatotoxicosis in sheep. In: Vet Hum Toxicol (1996 Apr) 38(2):89-91 ISSN: 0145-6296 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. Registry Numbers: 22888-70-6 (Silymarin) 50-99-7 (Glucose) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****VETERINARNI MEDICINA***** Vojtisek B Hronova B Hamrik J Jankova B [Milk thistle (Silybum marianum, L., Gaertn.) in the feed of ketotic cows] Ostropestrec mariansky (Silybum marianum, L., Gaertn.) v krmne davce ketoznich krav. In: Vet Med (Praha) (1991 Jun) 36(6):321-30 ISSN: 0375-8427 (Published in Czech) Two comparative trials were performed, each with 16 cows which in the period of 2-6 weeks after parturition had 7.9 mg and more acetone in 1 litre of milk. The cows, crossbreds of the Czech Red-Pied cattle with the Holstein cattle, were divided into control and test groups, eight in each using the system of pairs. The cows of test groups were given for a fortnight feed rations containing a meal of milk thistle (Silybum marianum, L., Gaert.) seeds, at a rate of 0.3 kg per head/day with the contents of 2.34% silybin and silydianin (substances of the so called silymarin complex of the flavonolignane group). In comparison with the control cows, in the blood and milk of the former ones a decrease was demonstrated in the sum of acetone + acetoacetic acid (up to P less than 0.01) and beta-hydroxybutyric acid in the blood (up to P less than 0.05). The ketonuria degree dropped remarkably. Although there were not observed any differences in the parameters of acid-base metabolism in the blood (pH, PCO2, BE, SB, BB), the pH values and net acid-base output in urine were higher in these cows. Milk production in the cows of control groups was decreasing during the trial (up to P 0.01), but in the test cows it was higher by 7.7% (trial 1) and by 3.4% (trial 2), in comparison with the milk yield at the beginning of the trials. Differences in metabolism parameters and milk production in favour of the cows which were given milk thistle in their feed rations were observed even in a fortnight after the diet stopped to contain this ingredient. Registry Numbers: 22888-70-6 (Silymarin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€