Silibinin
Silibinin, also known as silybin , is the major active constituent of silymarin, a standardized extract of the milk thistle, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silychristin, silidianin, and others. Silibinin itself is a mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio. Silibinin is used in pure forms as a medication, and more frequently as an active ingredient in milk thistle–derived herbal supplements.
Medical uses
For approved drug preparations and parenteral applications in the treatment of Amanita mushroom poisoning, the water-soluble silibinin-C-2',3-dihydrogensuccinate disodium salt is used. In 2012, the same compound also received Orphan Medicinal Product Designation for the prevention of recurrent hepatitis C in liver transplant recipients by the European Commission.Silibinin is available in many EU countries for treatment of toxic liver damage or as adjunctive therapy in chronic hepatitis and cirrhosis.
There is limited evidence to support use of silibinin-containing products as a supplement in people with chronic liver disease. A systematic review and meta-analysis concluded that silymarin does not affect all-cause mortality in persons with cirrhosis, but it may help prevent liver-related mortality in those patients. There is mixed evidence for silibinin as an anti-inflammatory agent in alcohol-related liver disease or non-alcoholic fatty liver disease, and trials continue. There is little evidence to support a meaningful antiviral effect of milk thistle in chronic hepatitis C.
Potential medical uses
Silibinin is under investigation to see whether it may have a role in cancer treatment.Silibinin has a number of potential mechanisms that could benefit the skin. These include chemoprotective effects from environmental toxins, anti-inflammatory effects, protection from UV-induced photocarcinogenesis, protection from sunburn, protection from UVB-induced epidermal hyperplasia, and DNA repair for UV-induced DNA damage. Studies on mice demonstrate a significant protection on chronic unpredictable mild stress –induced depressive-like behavior on mice and increased cognition in aged rats as a result of consuming silymarin. There is research on if it helps treat Metabolic dysfunction–associated steatotic liver disease.
Due to its immunomodulatory, iron-chelating, and antioxidant properties, this herb has the potential to be used in beta-thalassemia patients who receive regular blood transfusions and suffer from iron overload.
Pharmacology
Poor water solubility and bioavailability of silymarin led to the development of enhanced formulations. Silipide, a complex of silymarin and phosphatidylcholine, is about 10 times more bioavailable than silymarin. An earlier study had concluded Siliphos to have 4.6 fold higher bioavailability. It has been also reported that silymarin inclusion complex with β-cyclodextrin is much more soluble than silymarin itself. There have also been prepared glycosides of silybin, which show better water solubility and even stronger hepatoprotective effect.Silymarin, like other flavonoids, has been shown to inhibit P-glycoprotein-mediated cellular efflux. The modulation of P-glycoprotein activity may result in altered absorption and bioavailability of drugs that are P-glycoprotein substrates. It has been reported that silymarin inhibits cytochrome P450 enzymes and an interaction with drugs primarily cleared by P450s cannot be excluded.
Toxicity
Silibinin and all the other compounds found in silymarin, especially silychristin, blocked the MCT8 transporter according to one in vitro study. There is no published clinical information showing silymarin or silibinin cause any thyroid problems. In fact, one clinical trial found that silymarin actually helped prevent thyroid suppression that is often caused by the drug lithium.There is limited research on milk thistle and silymarin in pregnant humans. However, the one known clinical trial found only benefits, including but not limited to effectively treating intrahepatic cholestasis of pregnancy. Silymarin is also devoid of embryotoxic potential in animal models.
A phase I clinical trial in humans with prostate cancer designed to study the effects of high dose silibinin found 13 grams daily to be well tolerated in patients with advanced prostate cancer with asymptomatic liver toxicity being the most commonly seen adverse event.