Liver Disease/Milk Thistle (Silybum marianum)

By Tami Tabatabai

The Liver

The liver is the largest gland in the body and is responsible for a multitude of tasks that include the metabolism of proteins, carbohydrates and fats, production of bile, generation of energy, storage of vitamins and minerals and the detoxification of foreign substances (Vargas-Mendoza et al., 2014).

Livers are highly susceptible to damage, disease, and toxicity, which is worsened by obesity, unhealthy living, and the excess consumption of drugs and alcohol (Vargas-Mendoza et al., 2014). Most liver diseases are inflammatory in nature, with viral infections (hepatitis B and C), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease and autoimmune diseases being the most common causes of chronic inflammation (Ribeiro de Avelar, Pereira, Ribas de Farias Costa, Passos de Jesus & Magalhaes de Olieira, 2017). Milk thistle (Silybum marianum) is used in various liver disorders because it is a powerful anti-inflammatory, antioxidant and antifibrotic plant (Federico, Dallio & Loguercio, 2017).

Milk Thistle (Silybum marianum)

Silymarin, derived from the milk thistle plant, Silybum marianum, has been used for centuries as a natural remedy for diseases of the liver and biliary tract. … In this article we review silymarin’s history, pharmacology, and properties, and the clinical trials pertaining to patients with acute and chronic liver disease.

Milk thistle (Silybum marianum) is a popular medicinal plant that has been used for centuries as a hepatoprotectant, or liver protectant (Siegel & Stebbing, 2013). Native to the Mediterranean, milk thistle has milky sap and thorny branches with bright pink flowers (Vargas-Mendoza et al., 2014). Archeological evidence of Silybum marianum is located in an Egyptian Museum, indicating its use dating back to the Ancient Egyptian age, and likely related to its role in human health embodied on everyday historical Egyptian objects (Federico et al., 2017).

Flavonolignans are biological compounds known for their antioxidant properties. Silymarin, the extract of Silybum marianum, is a constituent of seven flavonolignans, one flavonoid, and the most prevalent class of compounds in the extract of milk thistle (Loguercio & Festi 2011).

Silybin, from the plant’s seeds, is the major constituent of silymarin accounting for approximately 50%-70% of silymarin extract, depending on the source of supplier, botanical material and the processes of extraction (Loguercio & Festi 2011). Silybin has low bioavailability, poor intestinal absorption and low water solubility (Loguercio & Festi 2011).

However, combining silymarin with phosphatidylcholine for better absorption and silibinin glycoconjugates for higher water solubility and strong antioxidant power allows for the safe and therapeutic use of silymarin (Federico et al., 2017).

Silymarin as a Hepatoprotectant

The chemical structure of silbyna A, silbyna B, isosilbyna A, and isosilbyna B, the extract of silymarin.

Free radicals that are produced from the metabolism of toxins and known to cause lipoperoxidation and cellular damage in the liver are inhibited by the antioxidant and hepatoprotective activities of silymarin (Vargas-Mendoza et al., 2014). Silymarin acts as an antioxidant primarily in the reduction of free radicals and as a lipid peroxidation inhibitor, which increases endogenous concentrations of enzymes known for their antioxidant reactions such as glutathione reductase, superoxide dismutase, glutathione peroxidase and catalase (Ribeiro de Avelar et al., 2017). Intracellular glutathione is affected by silymarin by preventing the lipoperoxidation of membranes (Vargos-Mendoza et al., 2014).

Silymarin has been shown to increase the synthesis of protein in hepatocytes by stimulating the activity of RNA polymerase I (Vargas-Mendoza et al., 2014), essential to cell growth and fundamental cellular functions (Goodfellow & Zomerdijk, 2013). Silymarin stabilizes hepatocyte cell membranes and prevents entry of toxic entry into the cells; further, silymarin binds to membrane receptors and inhibits toxins that try binding, which reduces any drug-induced hepatocellular damage (Ribeiro de Avelar et al., 2017).

With alcohol abuse, silymarin reduces cellular necrosis and lipid peroxidation while increasing cellular vitality (Federico et al., 2017).

Dosage

Pharmacokinetic studies have shown that the kinetics of silymarin is dependent on the type of liver disease being treated, that doses above 700 mg, at least three times daily, are needed to reach effective blood levels (Hellerbrand et al., 2016). At high doses, silymarin does not have adverse effects (Vargas-Mendoza et al., 2014).

Interactions and side effects

There have not been any clinically relevant interactions identified so far between other drugs and silymarin (Hellerbrand et al., 2016). However, care should be concerned with people allergic to ragweed.

References:

Federico, A., Dallio, M. & Loguercio, C. (2017). Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years. Molecules. Retrieved from https://www.mdpi.com/1420-3049/22/2/191

Goodfellow, S.J. & Zomerdijk, J.C.C.M. (2013). Basic Mechanisms in RNA Polymerase I Transcription of the Ribosomal RNA Genes. Subcellular Biochemistry. 61:10. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855190/

Hellerbrand, C., Schattenberg, J.M., Peterburs, P., Lechner, A. & Brignoli, R. (2016). The potential of silymarin for the treatment of hepatic disorders. Clinical Phytoscience. 2:7. Retrieved from https://clinphytoscience.springeropen.com/articles/10.1186/s40816-016-0019-2

Loguercio, C. & Festi, D. (2011). Silybin and the liver: From basic research to clinical practice. World Journal of Gastroenterology. 17(18): 2288-2301. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098397/

Ribeiro de Avelar, C., Pereira, E.M., Ribas de Farias Costa, P., Passos de Jesus, R. & Magalhaes de Olieira, L.P. (2017) Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis. World Journal of Gastroenterology. 23(27): 5004-5017. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526770/

Siegel, A.B., Stebbing, J. (2013). Milk thistle: early seeds of potential. Lancet Oncology. 14(10): 929-930. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116427/

Vargas-Mendoza, N., Madrigal-Santillan, E., Morales-Gonzalez, A., Esquivel-Soto, J., Esquivel-Chirino, C., Garcia-Luna, M. . . . Morales-Gonzalez, J.A. (2014). Hepatoprotective effect of silymarin. World Journal of Hepatology. 6(3): 144-149. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959115/