Silybum marianum, or milk thistle, frequently is utilized in the treatment of humans and animals with hepatic failure.
Milk thistle seed extracts have been used for centuries for liver protection.
Worldwide, researchers continue to show interest in milk thistle derivatives as a potential treatment for several diseases as evidenced by the over 12.000 related scientific publications produced on this subject within the last 10 years.
This review is confined primarily to the liver protective effects of milk thistle derivatives.
Nomenclature
Milk thistle is an annual herbaceous plant belonging to the tuboliflore compost family. It is found especially in central and southern Italy.
Silymarin is a standardized extract of milk thistle fruits and seeds containing at least 7 flavonolignans (including silibinin, isosilibinin, silychristin, isosilychristin, and silydianin) and 1 flavonoid (taxifolin).
Silibinin is the predominant compound in silymarin, composing 50–70%. Silibinin is not only the predominant ingredient in silymarin, but it also is considered to be the primary active ingredient.
For this reason, compounds containing milk thistle ingredients report silibinin content.
Farmacocinetica
Milk thistle extracts is usually administered per os.
The pharmacokinetics of milk thistle is crucial for therapeutic action.
There are two phase, primarily it is conjugated by glucuronidation and excreted into bile and urine with minimal.
The therapeutic action takes place thanks to phase II and to the metabolite silibinin glucuronide.
The metabolite Silibinin glucuronide, is transported by biliary flow to the intestinal tract where it undergoes cleavage by bacterial b-glucuronidase enzymes, restoring the silibinin parent compound and promoting enterohepatic circulation.
The bile silibinin concentrations are approximately 100x higher than serum concentrations.
Milk thistle extracts have low bioavailability when administered PO in most species.
Silibinin is relatively insoluble in water and is not absorbed readily from the intestines.
Bioavailability can be improved by combining milk thistle extracts with solubilizing substances.
Frequentemente è combinata con phosphaditilcolina.
Phosphatidylcholine increases oral bioavailability of silibinin in healthy humans and in patients with hepatic cirrhosis.
Commercially available milk thistle products are highly variable in content, dissolution,
and bioavailability, making it important to perform pharmacokinetic testing of products in the species of interest before clinical use.
Perhaps this is one of the reasons why its use in pets is controversial so the future study is working to evalutate dose, kinetics and treatment effect in domestic animals.
Preparation of silymarin in fluid-bed coated pellets and silibinin in sodium cholate/phospholipid-mixed micelles resulted in similar increased silibinin absorption in dogs.
FIT AROMA?
Farmacodynamica
Although milk thistle extracts have been used for centuries as a liver tonic, only recently has the mechanism
of hepatic protection become better understood.
Antioxidant
The mechanism of action best known is antioxidant free radical scavenging and inhibition of lipid peroxidation. Hepatic injury has long been linked to oxidative injury. Silibinin is most effective in scavenging low molecular weight free radicals, such as the hydroxyl radical.
Antiinflammatory
The main anti-inflammatory effect of silymarin appears to be linked to its ability to inhibit
nuclear transcription factor-κB (NF- κB) which regulates the expression of numerous implicated molecules
in inflammatory response, survival, growth and cell differentiation. In
detail NF- κB promotes the production of IL-1, IL-6, TNFα, INF-γ and GM-CSF (granulocyte
macrophage colony stimulating factor).
In human basophilic leukocytes it inhibits neutrophil-mediated histamine release. It also inhibits the
histamine release from rat peritoneal mast cells and into isolated Kupffer rat cells
synthesis of leukotriene B4 inhibited.
Antifibrotic
In vitro, the four isomers inhibited the activity of lipoxygenase and prostaglandin synthase.
Silibinin has been shown to have an antifibrotic effect in the liver.
Central to the onset of hepatic fibrosis is conversion of hepatic stellate cells to myofibroblasts, which is limited by silibinin by interruption of cell signaling. Silibinin decreases stellate cell DNA synthesis, proliferation, and migration.
Silibinin also limits fibrous tissue production. In a hepatic injury model in rats, silibinin administered PO decreased liver collagen concentration up to 55%.
Milk thistle extracts decreased markers of inflammation and fibrosis when used in combination with praziquantel an
in vivo model of schistosomal liver fibrosis.
Hepatoprotector
Hepatoprotective effects of silibinin in liver disease may be related to mechanisms of enhanced protein Synthesis. Sibilin binds to the DNA dependent RNA-polymerase I regulatory subunit in proximity of the estrogen binding site by acting as a natural steroidal effector; the increase of ribosomal RNA in the liver stimulates the formation of ribosomes and therefore the synthesis protein
Protein synthesis is necessary for hepatic regeneration and repair after toxic and inflammatory insults.
Another hepatoprotective effect of silibinin is a dose-dependent increase in bile flow (choleresis), primarily because of
stimulation of the rate of bile salt synthesis.
Toxicity
Studies demonstrated that toxicity is low in humans and animals, adding to the reputation of silibinin treatment as safe and no harmful.
Use
Milk thistle thanks to its protective and regenerative properties of liver tissue is an important and irreplaceable support in many liver injuries.
Improves the detoxifying abilities of the liver.
Specific activities are attributed to the flavonolignanic complex of silymarin: among these the hepatoprotective action against numerous agents toxic-metabolic
Silibinin is protective for Amanita intoxication when administered experimentally in dogs.
In dogs, silibinin limits changes in biochemical and coagulation parameters, decreases degree of hepatic hemorrhagic necrosis, and prevents death.
In addition to limiting oxidation, silibinin prevents transport of the phalloidin toxin into hepatocytes by competitive inhibition of hepatocytespecific OATP2 transporters.
Silibinin treatment has been shown to prevent increases in hepatic enzyme activity and other toxic changes in rats treated with carbon tetrachloride, 65,66 acetaminophen,67 and arsenic.
Milk thistle intervenes in the pharmacodynamics of many drugs and decreases their toxicity
In a study evaluating silibinin treatment combined with a hepatotoxic antituberculosis drug, hepatic enzyme activity was significantly decreased.
Silibinin also has been shown to be protective against radiation-induced hepatic injury and increases in hepatic enzyme activity, as well as that induced by doxorubicin.
Silibinin commonly is recommended for use in viral hepatitis.
Although silibinin has no known direct suppressive effects on viral replication, its use targets inhibition of inflammation and cytotoxic events secondary to viral infection.
Recent studies demonstrate improvement in liver enzyme activities and liver histology in patients with nonalcoholic fatty liver disease after silibinin treatment.
When silibinin was administered to peripartum dairy cows (in which subclinical fatty liver disease is common),
effects included improved lactation performance and improved body condition. In silibinin treated cows, only hepatocytes nearest the central vein were consistently affected, whereas in control cows, hepatocytes throughout the lobule contained cytoplasmic vacuoles.
Anti fibrotic properties reduce cirrhosis.
Hepatic cirrhosis is a common end result of advanced stages of alcoholic liver disease and viral hepatitis. Remodeling of hepatic architecture secondary to fibrosis can result in hepatic insufficiency, portal hypertension, and hepatic encephalopathy.Use of silibinin in hepatic cirrhosis results in improvement in antioxidant status, cytoprotection, reversal of fibrosis, and regeneration.
Conclusion:
The use of milk thistle has shown many benefits for the liver, these actions combined with extreme low toxicity make Silibinin an indispensable product in all liver suffering.
The hepatoprotective and choleretic action of milk thistle are recommended in all cases where you want to help the cleansing function of the liver metabolism.