• Clinical data 90%
  • Efficacy 80%
  • Security 70%
  • Toxicity 30%

Carduus marianus
Fructus Silybi Mariae


Carduus marianus L., Carthamus maculatum Lam., Cirsium maculatum Scop., Mariana mariana (L) Hill., Silybum maculatum Moench. Asteraceae are also known as Compositae.

General appearance

Obliquely obovoid with remainder of a flower crown on its top; 6–7mm long, up to 3mm wide, 1.5mm thick. Testa shiny brownish-black or matt greyishbrown, with dark or greyish-white dots. At the tip, there is a projecting yellowish cartilaginous, swollen ring, and at the bottom at the side, a canaliculate hilum. Silvery pappus absent from the drug. Varieties are white, grey and black.

Major chemical constituents

The major active constituents are flavonolignans (1.5–3.0%), collectively known as silymarin. The major components of the silymarin complex are the four isomers silybin and isosilybin (a 1 : 1 mixture of diastereoisomers), silychristin and silydianin. Other flavonolignans identified include 2,3-dehydrosilybin and 2,3-dehydrosilychristin. Taxifolin, a 2,3-dihydroflavonol, which may be regarded as the parent flavonol of the silymarin compounds, is another major marker for Fructus Silybi Mariae.

Medicinal uses

Uses supported by clinical data
Carduus marianus supportive treatment of acute or chronic hepatitis and cirrhosis induced by alcohol, drugs or toxins.
Uses described in pharmacopoeias and in traditional systems of medicine
Treatment of dyspeptic complaints and gallstones.
Uses described in folk medicine, not supported by experimental or clinical data
Treatment of amenorrhoea, constipation, diabetes, hay fever, uterine haemorrhages and varicose veins.


Most of the biochemical and pharmacological studies have been performed using a standardized silymarin preparation, or its major constituent, silybin.

Experimental pharmacology

Antioxidant activity

Silymarin and silybin have antioxidant activity in vitro: both react with oxygenfree radicals such as hydroxyl anions, phenoxy radicals and hypochlorous acid in various model systems such as human platelets, human fibroblasts, rat liver microsomes and mitochondria, and using enzymatically and non-enzymatically generated free inorganic radicals. The production of superoxide anion radicals and nitric oxide was inhibited after treatment of isolated rat Kupffer cells with silybin (IC50 80mmol/l). Both silymarin and silybin inhibited free radical induced lipid peroxidation in microsomal and mitochondrial preparations of human red blood cells, thereby stabilizing the structure of the cell membrane. Inhibition of cyclic AMP-dependent phosphodiesterase by silybin, silydianin and silychristin has been demonstrated in vitro. Since cyclic AMP is known to stabilize lysosomal membranes, an increase in the concentration of this nucleoside has been proposed to be the mechanism of membrane stabilization and thus the anti-inflammatory activity of silymarin. Silybin also inhibits phospholipid synthesis and breakdown in rat liver membranes in vitro, and corrects the alteration in phospholipid metabolism in ethanol-treated rats. Both silymarin and silybin are incorporated into the hydrophobic–hydrophilic interface of the rat microsomal membrane bilayer and alter the structure by influencing the packing of the acyl chains.

Antihepatotoxic activity

Silymarin and silybin inhibited hepatotoxicity induced by paracetamol (acetaminophen), amitriptyline, carbon tetrachloride, ethanol, erythromycin estolate, galactosamine, nortriptyline and tert-butyl hydroperoxide in rat hepatocytes in vitro. Silybin reduced ischaemic damage to nonparenchymal hepatic cells and improved post-ischaemic function in pig livers. Allyl alcoholinduced toxicity, and associated lipid peroxidation and glutathione depletion were suppressed after treatment of isolated rat hepatocytes with silymarin and silybin at concentrations of 0.1 and 1.0 mmol/l, respectively. Silybin stimulated macromolecular biosynthesis in vitro and in vivo. Silybin increased the rate of ribosomal RNA synthesis by 20% in rat liver, cultured hepatocytes and isolated liver nuclei, via activation of DNA-dependent RNA polymerase I. Silybin binds to the regulatory subunit of DNAdependent RNA polymerase I at the estrogen binding site, thereby acting as a natural steroid effector, and thus activating the enzyme and increasing the rate of ribosomal RNA synthesis. Silybin had no effect on the transcription of RNA polymerase II or III. The increase of ribosomal RNA synthesis in the liver stimulates the formation of mature ribosomes, and hence protein biosynthesis. Furthermore, an increase in DNA synthesis was observed in livers from hepatectomized rats treated with silybin (27mg/kg body weight).
Intraperitoneal or intragastric administration of silymarin (15–800mg/kg body weight) to dogs, mice and rats prevented carbon tetrachloride-induced liver damage. This effect of silymarin was attributed to its antioxidant activity, a decrease in the metabolic activation of carbon tetrachloride and stabilization of hepatocyte membranes. Intragastric administration of silymarin (50mg/kg body weight) improved the metabolism and tissue distribution of aspirin in rats with carbon tetrachloride-induced liver toxicity. Intraperitoneal administration of either silymarin or silybin markedly inhibited liver damage induced by paracetamol (acetaminophen), Amanita phalloides toxins (e.g. phalloidin and a-amanitin), ethanol, galactosamine, halothane, polycyclic aromatic hydrocarbons, rare earth metals (e.g. cerium, praseodymium and lanthanum) and thallium in various rodent models.
Furthermore, intravenous administration of silybin hemisuccinate sodium salt (50 mg/kg body weight) to dogs given sublethal doses of Amanita phalloides (85 mg/kg body weight) prevented the increase in concentration of liver enzymes in the blood and the decrease in clotting factors. The uptake of [3H]dimethyl phalloidin in isolated rat hepatocytes was inhibited by 79% in cells treated with silybin ester (100mg/ml). However, intravenous administration of silybin (50 mg/kg body weight) to rats inhibited the protective effect of ethanol on paracetamol-induced hepatotoxicity. The combination of ethanol and silybin appeared to lead to inhibition of paracetamol metabolism by microsomes. Intravenous administration of silybin hemisuccinate sodium salt (50 mg/kg body weight) to mice preinfected with sublethal doses of frog virus 3 attenuated histological changes in hepatocyte nuclei; animals treated with a lethal dose of frog virus 3 showed increased survival times. Intragastric administration of silymarin (50mg/kg body weight) to rats inhibited collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct occlusion induced by sodium amidotrizoate. Silymarin increased the redox state and the total glutathione content in the liver, intestine and stomach of rats after intraperitoneal administration (200mg/kg body weight). In a transplantation experiment, explanted pig liver was subjected to coldinduced ischaemia by storage of the liver at 4°C for 24 hours, followed by extracorporeal reperfusion for 4 hours. Intravenous administration of 500 mg silybin ester prior to removal of the liver, followed by 400 mg/l during cold storage and 100mg/h during reperfusion, reduced histological damage to the liver cells (measured by bile production) and improved liver function during reperfusion by 24–66% (measured by bile acid excretion).

Anti-inflammatory and anti-allergic activity

Silybin inhibited neutrophil-mediated histamine release induced by f-met peptide and anti-IgE from human basophil leukocytes. The inhibitory effect was significantly attenuated (P < 0.05) by elevating the extracellular calcium concentration. However, no effect was observed on histamine release induced by the calcium ionophore A23187. Silymarin inhibited neutrophil-mediated histamine release activated by N-formylmethionyl-leucyl-phenylalanine from rat peritoneal mast cells at a concentration of 25mg/ml. Silybin inhibited the synthesis of leukotriene B4 (IC50 15mmol/l) in isolated rat Kupffer cells, but had no effect on prostaglandin E2 formation at concentrations up to 100mmol/l. Silymarin, silybin, silydianin and silychristin inhibited the activity of lipoxygenase and prostaglandin synthetase in vitro. The antiinflammatory activity of silybin was assessed in human polymorphonuclear leukocytes in vitro. The chemotactic and phagocytic activities of the polymorphonuclear leukocytes were not modified by silybin at concentrations of 0.5 25.0mg/ml. However, the compound did inhibit luminol-enhanced chemiluminescence, suggesting that the mechanism of anti inflammatory activity involved the inhibition of hydrogen peroxide formation. Intragastric administration of silymarin reduced carrageenan-induced footpad oedema in rats (ED50 62.42 mg/kg body weight). Topical application of silymarin inhibited xylene-induced ear inflammation in mice, and its activity was similar to that of indometacin (25 mg/kg body weight). In addition, silymarin inhibited leukocyte accumulation in inflammatory exudates following intraperitoneal administration of carrageenan to mice. Intragastric administration (25–1000mg/kg body weight) of an acetone extract of the fruit containing silybin increased the volume and dry mass of excreted bile in rats. Intragastric administration of silymarin (100mg/kg body weight) prevented gastric ulceration in rats induced by cold-restraint and pyloric ligation, but was not effective against ethanol-induced ulcers. Intragastric administration of silymarin (100 mg/kg body weight) to rats prevented gastric injury induced by ischaemia-reperfusion.

Clinical pharmacology

Alcohol-induced hepatitis

The efficacy of a standardized silymarin preparation for the treatment of alcohol-induced cirrhosis was assessed in six placebo-controlled clinical trials. The majority of these studies involved between 50 and 100 patients, with one study including 170 patients. Patients generally received an oral dose of 280–420mg (140mg two or three times daily) of a standardized silymarin preparation or placebo. One of the studies had a treatment period of up to 4 years, and used survival rates as their outcome parameter.
The results of this study showed a significant decrease in the mortality of patients treated with silymarin as compared with placebo (P < 0.05). After treatment with the silymarin preparation (140 mg twice daily), a decrease in total bilirubin, liver enzymes and serum N terminal propeptide of collagen type III levels was observed. A 6-month trial that was also double-blind assessed the efficacy of silymarin in patients who had histological documentation of chronic alcoholic hepatitis. Silymarin treatment improved histology, and lymphocyte proliferation and lipid peroxidation. In two studies that were also randomized and double-blind, treatment of 163 patients with the silymarin preparation decreased serum levels of liver enzymes, improved liver function, and returned sulfobromophthalein levels to normal, as compared with placebo. Another trial that was also randomized and doubleblind analysed the effects of silymarin in 116 patients with alcohol-induced hepatitis, 58 of whom had liver cirrhosis. Patients received 420mg silymarin or placebo daily for 3 months. A significant improvement was noted in both groups (P < 0.05); however, silymarin was not more effective than placebo. Five double blind clinical trials assessed the efficacy of silymarin in the treatment of various chronic liver diseases induced by alcohol. In four of these trials, treatment of patients with 420 mg of the silymarin preparation daily for 6 months decreased the serum levels of bilirubin, procollagen III peptide and liver enzymes, and increased serum glutathione peroxidase activity and lectin-induced lymphoblast transformation. In the fifth study, which was also placebo-controlled, the efficacy of silymarin wasassessed in 20 patients with various chronic liver diseases. After 13 months of  treatment (420 mg daily), histopathological findings showed improvements in the treated group as compared with the group that received placebo. In a randomized trial of 60 patients with diabetes caused by alcohol induced cirrhosis, patients received either 600 mg silymarin daily or no treatment for 6 months. The blood glucose and malondialdehyde levels, daily insulin need and fasting insulinaemia levels were all significantly lower in treated patients than in those that were untreated (P < 0.05), and lower than initial baseline values. A study without controls assessed the efficacy of a standardized silymarin preparation (420 mg daily) in inhibiting fibrotic activity in 277 patients with various chronic liver diseases. In liver fibrosis, the serum level of the procollagen III peptide increases. The elevated levels of this peptide decreased over the 4-week treatment period. In a drug monitoring study without controls, 108 patients with alcohol-induced hepatotoxicity and liver inflammation were treated with silymarin (200–400mg/kg body weight, in a single dose) daily for 5 weeks. After treatment, the serum procollagen IIIpeptide and liver enzyme levels were lower in comparison to the initial baseline values. The preparation was generally well tolerated in 98% of patients. The safety and efficacy of silymarin were evaluated in over 3500 patients in two drug-monitoring studies. In one study, 2637 patients with various liver disorders were treated with a standardized silymarin preparation (560mg, given in four divided doses) daily for 8 weeks. Subjective symptoms decreased by 63%, clinical findings improved and elevated serum levels of liver enzymes were reduced in the treated group. Treatment was rated as very good, good or satisfactory by 88% of the physicians. Minor gastrointestinal side-effects were reported in 1% of patients.


Fructus Silybi Mariae is contraindicated in cases of known allergy to plants of the Asteraceae family.


No information available.

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