SILYMARIN

Common name: Marian thistle, St. Mary’s Thistle , Holy thistle, Silymarin

Scientific name: Silybum marianum

Description of the plant:

• Milk thistle (Silybum marianum), a member of the Compositae family, is an annual or biennial native to the Mediterranean, but now widespread throughout the world. The main stem is stout, ridged with branching. Milk thistle has the white patches, or marbling along the veins of the dark green leaves. (7)
• The broad leaves are deeply lobed, and basal leaves can be 20 inches long and 10 inches wide. The leaf margins are yellow and tipped with woody spines 1/8" to 1/2" long. The leaves are alternate, and clasping to the stem. (7)
• The stem leaves are smaller and not quite as lobed. Each stem ends in a solitary composite flower head, about two inches in diameter, consisting of purple disc flowers. (7)
• The flower head of milk thistle differs from other thistles with the presence of broad leathery bracts that are also tipped with stiff spines ¾ inch to two inches long. (7)
• The seeds are heavy, ¼ inch long, flat, smooth, and shiny and the colour ranges from black to brown mottled and have a tuft of minutely barbed bristles, which is deciduous, and falls off in a ring when the seeds mature.(7)
• Milk Thistle is an annual or biannual plant. Grows up to 2 meters in height. It has a firm, ridged main stem, and deeply lobed, alternately arranged along the stem. Leaves are dark green with yellow, spiny margins. Each stem ends with a single flower head, with purple disc flowers.(1)
• Milk thistle is a flowering herb native to the Mediterranean region. It has been used for thousands of years as a remedy for a variety of ailments, and historically was thought to have protective effects on the liver and improve its function.(8)

Parts: The dried, ripe fruits or achenes (“seeds”).(4)

SEEDS

ACTIVE CONSTITUENTS:

• The active ingredient in milk thistle is a flavonoid complex known as silymarin, which is extracted from the seeds of the plant.1, 2 The standardized seed extract contains approximately 70-80% of silymarin flavolignans, and around 20-40% of a fraction of polymeric and oxidized polyphenolic compounds which has not been chemically defined.1 The six major flavolignans are silybin A and B, isosilybin A and B, silychristin, and silydianin. These compounds are likely the main contributors to silymarin’s beneficial effects. In particular, silybin, also known as silibinin, has been studied for its effectiveness in liver treatment and other applications.(2)

Traditional use:

• Milk thistle (Silybum marianum) has a long and important history in herbal medicine  dating back over 2,000 years in European herbal traditions. Dioscorides, an early Greek  physician in Rome used the herb to induce vomiting. Pliny the Elder described its use in  “carrying off bile” and as this historical gastrointestinal and liver connection grew, 15^th and 16th century physicians described it as a liver and blood cleansing herb. In the late  16th century, Culpepper used is as a remedy for obstructions of the liver and the spleen, and specifically the infusions from the fresh root and seed for jaundice and for  dissolving and excreting gall stones.(11)
• Milk thistle is a plant with a long history in medicine, having been mentioned in every important medicinal record of herbs.It was widely used as a medicinal plant in traditional European medicine, and its seeds have been used for over 2000 years for a variety of purpose. (2)
• Traditional uses have mainly focused on the treatment of liver diseases, but have also included gallbladder disorders such as hepatitis, cirrhosis and jaundice.1 Milk thistle was brought to North America with European immigration, and was used there as a treatment for such various ailments as gallstones, morning sickness, uterine hemorrhage, and congestion of the liver, spleen or kidneys.(2)

Traditional use:(5)

·         Protects liver from toxins, heavy metals, alcohol, poisons.

·         Liver disease, acute and chronic hepatitis.

·         Treatment of fatty degeneration of liver,. Liver cirrhosis.

·         Psoriasis.

·         Gallbladder disorders.

·         Indigestion

Pharmacological Activity:

• Silymarin is not water soluble, making tea preparations ineffective; therefore it is usually administered orally in encapsulated form. Because absorption of silymarin from the gastrointestinal tract is only moderate (23-47%), it is best administered as a standardized extract of 70-80 percent silymarin. In animals and humans, peak plasma levels are reached in four to six hours after an oral dose. Silymarin is excreted primarily via the bile but some clearance is also achieved via the kidneys. The clearance half-life of silymarin is six to eight hours  mechanism of action.Silymarin is not water soluble, making tea preparations ineffective; therefore it is usually administered orally in encapsulated form. Because absorption of silymarin from the gastrointestinal tract is only moderate (23-47%), it is best administered as a standardized extract of 70-80 percent silymarin. In animals and humans, peak plasma levels are reached in four to six hours after an oral dose. Silymarin is excreted primarily via the bile but some clearance is also achieved via the kidneys. The clearance half life of silymarin is six to eight hours.(9)
• German scientists made a breakthrough in the late 1960s when they isolated the liver-protectant principles in the fruit .They called these Silymarin. Milk Thistle contains three potent liver protective flavonoids- Silybin, Silydianin & Silychristin known collectively as Sylimarin.(5)
• Numerous clinical trials have shown that Silymarin protects the liver. Silymarin protects the liver against various toxins and boasts another remarkable property: namely, by encouraging the regeneration of liver cells, it can actually reverse the damage and help cure the liver. It does this by stimulating protein synthesis [RNA polymerase A ], thus activating the liver,'s ability to regenerate itself through increased formation of new liver cells called hepatocytes.(5)
• Silymarin counteracts the toxic effects of a wide variety of liver poisons, including alcohol, carbon tetrachloride (used widely in the dry-cleaning industry) acetaminophen and the death cap mushroom, which can cause death within a day.(5)
• The mechanisms of action of Silymarin are as follows:

1.         Altering the membranes of hepatic cells to inhibit passage of toxins.

2.         Increasing cellular regeneration by stimulating protein synthesis.

3.         Increasing glutathione levels in liver cells.

4.         Scavenging for substances called free radicals that can damage the liver -because of it's powerful anti-oxidant properties in the liver cells, stomach and intestine.(5)
As a result, Silymarin ( at a dose of 140 mg. three times daily), can significantly reduce patient mortality in alcohol-induced liver cirrhosis. Acute viral hepatitis can be treated with Silymarin ( at a dose of 70 mg. three times daily) to lower levels of bilirubin and the transaminases (liver enzymes).(5)

Silymarin has also been used in death angel or death cap mushroom poisoning , and fatal outcome can be prevented if treatment is begun at an early stage.(5)

Clinical Indications:

Amanita Mushroom Poisoning

• The most impressive use of silymarin is in the treatment of Amanita phalloides mushroom poisoning.(9)
• The genus Amanita is widespread in Europe and North America with several edible species being prized by mushroom collectors. Unfortunately, many of the Amanita species are highly toxic, and ingestion results in severe liver damage and death in approximately 30 percent of cases.24 In animal studies, silymarin given within 10 minutes after amanita toxin ingestion completely counteracted the toxic effects, and if given within 24 hours of toxin ingestion silymarin prevented death and greatly reduced liver damage.(9)

Hepatitis

• Studies have shown silymarin to be effective in the treatment of both acute and chronic hepatitis. In acute viral hepatitis, administration of silymarin shortened treatment time and lowered serum bilirubin, AST, and ALT. In patients with chronic hepatitis, 420 mg silymarin per day for six months also yielded improved serum liver enzymes.(9)

Alcoholic Liver Disease and Cirrhosis

• Studies conducted in Austria and Hungary have demonstrated silymarin administration resulted in a normalization of serum liver enzyme and total bilirubin levels in patients with alcoholic liver disease, in addition to improved liver tissue histology. In patients with cirrhosis, long-term (41 months) administration of silymarin at 420 mg per day resulted in a significant increase in survival compared to the placebo group.(9)

Hypercholesterolemia

• An animal study found silymarin given to rats with diet-induced hypercholesterolemia demonstrated an anticholesterolemic effect similar to probucol, with an increase in HDL cholesterol and a decrease in total and biliary cholesterol.(9)

Psoriasis

• The value of silymarin in the treatment of psoriasis may be due to its ability to improve endotoxin removal by the liver, inhibit cAMP phosphodiesterase, and inhibit leukotriene synthesis. Abnormally high levels of cAMP and leukotrienes have been observed in patients with psoriasis and normalization of these levels may improve the condition.(9)

Toxicity:

• The acute toxicity of silymarin has been studied in mice, rats, rabbits and dogs after intravenous infusion. The 50% lethal dose (LD50) values are 400 mg/kg in mice, 385 mg/kg in rats and 140 mg/kg in rabbits and dogs. However, these values are only approximate, as they depend on the infusion rate. When the compound is given by slow infusion (over 2 to 3 hours), values of 2 g/kg may be recorded in rats. After oral administration tolerance is even higher, with values over 10 g/kg. In the event of acuteintoxication, the cause of death seems to be cardiovascular failure. Similar results have also been obtained by Vogel et al.(10)
• Other experiments to assess the acute toxicity of silymarin were performed in beagle dogs, rabbits, Wistar rats and NMRI mice after an intravenous bolus dose. Silymarin was used as the hemisuccinate sodium salt and the animals were kept under observation for 14 days. The LD50 was 1050 and 970 mg/kg in male and female mice, respectively, and 825 and 920 mg/kg in male and female rats, respectively. The mean lethal dose for rabbits and the maximum tolerated dose in dogs were calculated to be about 300 mg/kg. These data demonstrate that the acute toxicity of silymarin is very low. Similarly, its subacute and chronic toxicity are very low; the compound is also devoid of embryotoxic potential.(10)
• Toxicity is very low, the oral 50% lethal dose being 10 000 mg/kg in rats and the maximum tolerated dose being 300 mg/kg in dogs. Moreover, silymarin is devoid of embryotoxic potential.(6)
• In conclusion, silymarin is a well tolerated and effective antidote for use in hepatotoxicity produced by a number of toxins, including A. phalloides, ethanol and psychotropic drugs. Numerous experimental studies suggest that it acts as a free radical scavenger, with other liver-specific properties that make it a unique hepatoprotective agent.(6)

REFERENCES:

1.  “Health From Nature” Team.2011.Health From Nature.net. Milk Thistle Silybum marianum. http://health-from-nature.net/Milk_Thistle.html
2. ADVANCES in orthomolecular research.2012.Milk Thistle A Historical Liver TreatmentVol3.Issue6. http://www.aor.ca/wp-content/uploads/2012/10/Advances-Vol3-6-Detox-Milk-Thistle.pdf
3. Armando González Stuart, Ph.D., 2005.Milk Thistle. Silybum marianum (L.) Gaertn. http://www.herbalsafety.utep.edu/herbs-pdfs/milkthistle.pdf
4. Campos, R. et al. (1989) Silybin Dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Medica. 55:417. http://www.rxmed.com/b.main/b3.herb.monos/b3.1.monographs/milk.thistle.html
5. Fraschini, F.,Demartini, G.,Esposti, D.2002. Clin Drug Invest 22(1):51-65.Pharmacology of Silymarin. http://drug.pharmacy.psu.ac.th/wbfile/410254820581.pdf
6. Kaur, A.K., Wahi, A.K., Kumar, B., Bhandari, A., Prasad, N.Department of Pharmacy, Jodhpur National University, Jodhpur, Gyani Inder Singh Institute of Professional Studies. 2001. International Journal of Pharma. Research & Development – Online(IJPRD).MILK THISTLE (SILYBUM MARIANUM). http://www.ijprd.com/MILK%20THISTLE%20(SILYBUM%20MARIANUM)%20_%20A%20REVIEW.pdf 
7. NCAAM Publication.2012.National Center for Complementary and Alternative Medicine (NCCAM).Milk Thistle. http://nccam.nih.gov/health/milkthistle/ataglance.htm
8. Thorne Research, Inc.1999. Alternative Medicine Review .Vol 4.p.273.http://www.thorne.com/altmedrev/.fulltext/4/4/272.pdf
9. Tori Hudson, ND. MILK THISTLE (Silybum marianum).Hepatoprotection at its best. http://www.integrativepractitioner.com/uploadedFiles/ResearchReview-of-MilkThistle-Gaia.pdf
10. V. Křen, D. Walterová.2005.Biomed Papers. SILYBIN AND SILYMARIN – NEW EFFECTS AND APPLICATIONS. http://mefanet.upol.cz/BP/2005/1/29.pdf

                                                  

COMPILED BY:  MALALU-AN, MARY LOUISSE A.