Much of the laboratory studies have been done in the unfortunately usual mode of pharmacology. This author in no way endorses or supports animal experiments with herbs. The reasons are discussed at length elsewhere. The reasons for introducing such tainted research findings here is to illustrate the way in which such science is "proving" to itself what herbalist's already know.

Of the herbs discussed here Carduus is more often used in Europe and North America, Glycyrrhiza in Japan, Schizandra in China, and Bupleurum in Japan and China.

In laboratory tests a range of effects have been demonstrated including:

• silymarin reduced the harmful actions on the liver of hepatotoxins such as carbon tetrachloride, thioacetamide, a-amanitin and phalloidin.
• a protective effect against carbon tetrachloride induced liver damage in rats.
• a reduction of the prolongation of hexobarbital sleeping time produced by carbon tetrachloride. This is a common method for assessing protective effects on the liver against the effects of chemical toxins. Hexobarbital causes a consistent pattern of sleep in the unfortunate experimental animals, and any change in sleep time reflects some disturbance of the liver ability to metabolize the sedative. An increase in sleeping time implies impairment of the livers ability to metabolize the hexobarbital. Carbon tetrachloride produces such a change. When Milk Thistle is added the increase in sleeping time normally produced by the carbon tetrachloride is reduced by up to 60%, suggesting that the herb is protecting liver function from the toxin.
• prevention of the inhibition of hepatic metabolism of p-oxyphenylpyruvic acid (OH) caused by carbon tetrachloride. This chemical is metabolized exclusively in the liver during the degradation of tyrosine. Any unmetabolized OH is excreted in the urine, thus, its level in the urine increases following the administration of a liver toxin. Substances that counteract the toxin bring urine OH levels back to normal. Histological studies of the liver reveal how much structural damage has occurred. The histological finds from carbon tetrachloride poisoning is very similar to that of hepatitis, and it increases OH levels in the urine dramatically. Milk Thistle significantly counteracts the effects of the carbon tetrachloride, so much so, that the results are almost indistinguishable from controls.
• carbon tetrachloride raises serum levels of enzymes such as glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH), but under treatment with silymarin these increases were significantly diminished.
• i.p. injection of D-galactosamine (GalN) to rats causes an acute hepatitis that is similar to viral hepatitis in humans. Silymarin has a protective action against such liver lesions.
• poisoning with DL-ethionine leads to accumulation of triglycerides in the liver of rats. Silymarin inhibited such increases.
• it counteracted the effects of cadmium, an pollutant that accumulates in human tissues over time, causing hypertension, liver, kidney & neural damage, and hemorrhagic necrosis of the liver and testes. Milk Thistle pretreatment almost completely prevented death and necrosis whilst reducing nerve damage.
• the hepatotoxic salts of such rare earth metals as praseodymium, indium and cerium cause necrosis and fatty degeneration in the liver. Pretreatment with Milk Thistle reduces or prevented this altogether. The researchers suggest a number of possible mechanism:
  • that it facilitates a more rapid elimination of the metals from the body
  • it stimulates the formation of metal-binding proteins which detoxify the metals
  • it may inhibit the binding of these metals with cells at receptor sites
• thioacetamide is a hepatotoxin which causes a development of conditions in rats that are similar to human liver. When silymarin was given with the poison in the feed, animals lost less weight and their survival times increased. Injecting thioacetamide increases the serum levels of the enzymes GPT, GOT, SDH, and glutamate dehydrogenase, which were also prevented by silymarin.
• it partially counteracts alcohol damage to the liver.
• mitochondrial changes caused by ethanol are almost completely prevented by silymarin.
• ethanol increases malondialdehyde formation and spontaneous chemiluminescence in the rat liver. Silymarin given prior to the ethanol suppresses both effects completely.
• Milk thistle has an extraordinary hepato-protective effect, blocking damage from the toxins of the Avenging Angel mushroom Amanita phalloides, phalloidin and a-amanitin. It has both protective and curative effects on survival time and death rate of mice after administration of a-amanitin, also antagonizing the toxicity of phalloidin. It inhibits the loss of weight observed in poisoned animals. Animals fed sub-lethal doses of amanitine lose weight very rapidly and gain it back very slowly. Animals fed a combination of amanitine and Milk Thistle lose weight much more slowly and gain it back much more rapidly. It greatly increased life-span in the poisoned animals. When administered later than 20 minutes after poisoning, it was no longer possible to detect any anti-hepatotoxic effect, suggesting that silymarin prevents penetration of the toxins by competing for the same receptor sites on cell membranes.
• it has blocked the hepatotoxic effects of some viruses on laboratory animals.
• silybin enhances ribosomal RNA synthesis as a result of the stimulation of DNA-dependent RNA-polymerase A.

1. an alteration of cell membranes, such that only small amounts of toxins may penetrate into the cell
2. an acceleration of protein synthesis, thus stimulating cell regeneration.