Silymarin is a flavonolignans extracted from the milk thistle Silybum marianum (L.) gaernt. Silymarin has been shown to possess various pharmacological properties like hepatoprotective, antioxidant, anti-inflammatory, anticancer, and cardioprotective activities. Although it has been proved by clinical trials that silymarin is safe at high doses (>1500 mg/day) in humans, pharmacokinetic studies revealed poor absorption, rapid metabolism, and ultimately poor oral bioavailability of silymarin.(https://www.sciencedirect.com/topics/medicine-and-dentistry/silymarin)
Widespread use of herbal drugs because of their protective effects on different organs toxicity has been shown in many studies. These protective effects have been illustrated in the fields of nephrotoxicity, hepatotoxicity, viral hepatitis, cancer, in vitro fertilization, neurotoxicity, depression, lung diseases, prostate diseases etc. Silymarin has cytoprotection activities due to its antioxidant activity and radical scavenging. The possible known mechanisms of action of silymarin protection are blockade and adjustment of cell transporters, p-glycoprotein, estrogenic and nuclear receptors. Moreover, silymarin anti-inflammatory effects through reduction of TNF-α, protective effects on erythrocyte lysis and cisplatin-induced acute nephrotoxicity have been indicated in some studies. Silymarin has also inhibited apoptosis and follicular development in patients undergoing IVF. Basis on such data, silymarin can be served as a novel medication in complementary medicine.
Silybum marianum L. (Milk thistle), a member of Carduus marianum family, is an ancient medicinal plant which has been used for centuries for treatment of different diseases such as liver and gallbladder disorders, protecting liver against snake bite and insect stings, mushroom poisoning and alcohol abuse. This plant can be found in Kashmir, North America, Canada and Mexico with large leaves and a reddish-purple flower that are all thorny and the medicinal part of the plant is either the seeds or fruits.
Milk thistle was first grown in Europe and used as a liver tonic as it was said to be able to open the obstructions of the liver and spleen, and thereby was good for jaundice. Moreover, this herb has been used for centuries as a natural treatment for upper gastrointestinal tract and digestive problems, liver and biliary tract diseases, menstrual disorders and varicose veins.
The very first usage of Milk thistle, however, was for its hepatoprotectant and antioxidant activities. Silymarin is the active component of this herb, which is a complex of other components, mainly silybin A, silybin B, isosilybin A, isosilybin B and also other flavonolignants such as silychristin, neosilyhermin, silyhermin and silydianin which exists in its fruit and seeds more than the other parts.
Different mechanisms of action of silymarin are as follow:
- Increasing the regenerative ability of the liver cells by enhancing the synthesis of DNA and RNA, as silymarin has a steroid structure;
- Altering the structure of the hepatocyte external membrane, that prevents entrance of the xenobiotics into the cell (poisoning with Amanita mushroom is a noteworthy example of such mechanism);
- Scavenging free radicals and increasing the cellular content of glutathione that leads to the inhibition of lipid peroxidation;
- Another mechanism of action of silymarin is modifying the transporters and receptors of cell membranes such as ABC transporters (P-gp), organic anion uptake transporter peptides (OATP), bile salt export pump, and TNF-α-dependent transporters