Silymarin Chemical Properties

Melting point:

158 °C

storage temp. 

-20°C

solubility 

Acetone (Slightly), DMSO (Slightly), Methanol (Very Slightly)

form 

Solid

color 

Light Orange to Brown

InChI

InChI=1S/C25H22O10/c1-32-17-6-11(2-4-14(17)28)24-20(10-26)33-18-7-12(3-5-16(18)34-24)25-23(31)22(30)21-15(29)8-13(27)9-19(21)35-25/h2-9,20,23-29,31H,10H2,1H3

InChIKey

FDQAOULAVFHKBX-UHFFFAOYSA-N

SMILES

C1(C2=CC=C3OC(C4=CC=C(O)C(OC)=C4)C(CO)OC3=C2)OC2=CC(O)=CC(O)=C2C(=O)C1O

CAS DataBase Reference

65666-07-1(CAS DataBase Reference)

Safety Information

Safety Statements 

22-24/25

WGK Germany 

3

MSDS

• Language:English Provider:SigmaAldrich

Silymarin Usage And Synthesis

Description

Silymarin(65666-07-1) is a kind of flavonoid complex consisting of silybin, silydianin, and silychrisin, derived from the milk thistle plant. It is a kind of potent antioxidant, anti-cancer agent as well as liver protecting agent. It has a lot of pharmaceutical functions. For example: (1) Promotes healthy liver function and general health; (2) Strengthen the normal cellular defense system to protect the liver tissue; (3) Help to eliminate the toxin accumulating in the liver; (4) Increase the survival rate of patients of cirrhosis; (5) Protect our body against industrial poisons; (6) Antidote against the death cap mushroom. Silymarin exerts its pharmaceutical effects through various mechanism including scavenging free radicals, increasing glutathione (has detoxifying effect) level in the liver, increasing the levels of antioxidant enzymes such as superoxide dismutase, stimulating liver protein synthesis and inhibiting the synthesis of leukotrienes.

Physical properties

Silymarin is obtained from silybum marianum (milk thistle), an edible plant that has been used medicinally for centuries as a herbal medicine for the treatment of liver related disorders. The plant is native to the Mediterranean andis widely found in Europe and North America. It also grows in India, China, South America and Australia. This herb is approved for sale in Canada in different products and gains an annual business of 180 million in Germany.

Silymarin is a polyphenolic flavonoid, extracted using 95% ethanol, from the seeds of the milk thistle. The plant consists of approximately 70-80% of silymarin flavonolignans and approximately 20-30% undefined fraction. The most prevalent component is Silybin (50-60% of Silymarin). It consists of seven flavonoglignans (silibinin, isosilibinin, silychristin, isosilychristin and silydianin) and a flavonoid (taxifolin).

Pharmacokinetics

Silymarin is insoluble in water and is often administered in a capsulated form. It is absorbed orally, with peak plasma concentration in 6-8 hr. But, the oral absorption of silymarin is only about 23-47% leading to low bioavailability. The poor water solubility and bioavailability led to the development of enhanced formulations like silipide (Siliphos) a complex of silymarin and phosphatidylcholine which is ten times more bioavailable.

Mechanism of action

Silymarin's hepatoprotective effects are accomplished by several mechanisms which include antioxidant, inhibition of lipid peroxidation, enhanced hepatocyte regeneration, enhanced liver detoxification and protection from glutathione depletion, antiinlammatory effects including inhibition of leukotriene, prostaglandin synthesis and kupffer cells, mast cell stabilization. slowing of fibrosis by reducing conversion of hepatic stellate cells.
Silymarin is a naturally-occurring polyphenolic flavonoid compound. Silymarin is derived from the seeds of the milk thistle plant. It has inhibitory effects on melanogenesis in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. In one study (Choo et al., 2009), silymarin was shown to significantly prevent melanin production in a dose-dependent manner with an IC50 value of 28.2 μg/ml, without effects on cell viability (Choo et al., 2009). Also, silymarin inhibits the L-DOPA oxidation activity of the rate-limiting melanogenic enzyme tyrosinase in cell based-systems but it does not directly affect cell-free tyrosinase activity (Choo et al., 2009). Furthermore, silymarin decreases the expression of tyrosinase protein (Choo et al., 2009).

Uses

In the United States, milk thistle(65666-07-1) is most commonly used to treat viral infections and cirrhosis of the liver. Milk thistle (Silybum marianum) was used in classical Greece to treat liver and gallbladder diseases and to protect the liver against toxins. It recently has been investigated for use as a cytoprotectant, an anticarcinogen, and a supportive treatment for liver damage from Amanita phalloides poisoning. Its active ingredient is silymarin, found primarily in the seeds. Silymarin undergoes enterohepatic recirculation, which results in higher concentrations in liver cells than in serum.It is made up of components called flavonolignans, the most common being silybin.

Side effects

Silymarin has very low toxicity and has been shown a good safety profile. At high doses it has a laxative effect due to increased bile secretion, adverse effects related to GI tract were reported in 2-10% patients in a clinical trial.

References

http://www.smart-publications.com/articles/silymarin-a-potent-antioxidant-liver-protector-and-anti-cancer-agent/page-2
http://172.16.24.181/www.mediherb.com/media/797348/silymarin-pds.pdf

Uses

Silymarin a flavonolignan complex extracted from milk thistle, has been shown to provide cytoprotective, antioxidant and hepatoprotective effects. Provides extracts such as (+)-taxifolin as an inhibitor of β-amyloid aggregation.

Uses

Silymarin has been used to study:

• its in vitro antiviral, antibacterial, antifungal activities and cytotoxicity
• its effect of silymarin on bladder contractions in cyclophosphamide (CYP)-induced cystitis rat model
• its effect on liver toxication induced by Fumonisin B1 in mice

Indications

Milk thistle (Silybum [Carduus] marianus) is a spiny European plant with white-veined leaves and milky sap, the seed of which is used to treat liver disease.Milk thistle seed extract is used orally in the treatment of alcoholic and other cirrhoses and in Europe intravenously for its hepatoprotective effect in Amanita and other mushroom poisonings. It is grown in this country primarily as a “liver cleanser” and is reputed to protect this organ from a wide array of toxins.Milk thistle seed contains the active principle silymarin, a complex of flavonolignan compounds including silibinin (silybin), silidianin, and silychristin.

Definition

ChEBI: 3,5,7-trihydroxy-2-[3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-3,4-dihydro-2H-1-benzopyran-4-one is a flavonolignan.

General Description

Silymarin is a flavonolignan, obtained from milk thistle (Silybum marianum) plant.

Biochem/physiol Actions

Silymarin was shown to protect the liver from the cytotoxic effects of anti-tuberculosis drugs by decreasing serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels. This effect was related to the anti-oxidant effects of silymarin.

Mechanism of action

Silybum marianum (milk thistle) contains numerous phytocompounds, such as silymarin and silibinin, demonstrating antioxidant and anti-inflammatory activity. Silibinin has strong protection against UV-induced damage by inhibition in both cell proliferation and apoptosis by reducing thymine dimer-positive cells and upregulating p53 in mice. Increasing the transcriptional activity of p53 leads to the synthesis of p21/Cip1, a protein that arrests DNA synthesis and thereby increases DNA repair time.

Mechanism of action

Silymarin is thought to protect the liver by preventing the entry of toxins into the hepatocyte and by stimulating nucleolar polymerase A, which, in turn, increases protein synthesis and liver regeneration. Silymarin undergoes enterohepatic circulation, increasing its concentration in hepatocytes. It is also an antioxidant in its own right and is considered to have some cytoprotective effect against carcinogens.

Clinical Use

Alcoholic cirrhosis has been improved (faster return of liver enzymes to baseline) in at least three trials, although one multicenter Spanish study failed to demonstrate any change in the clinical course.There is no evidence to support the use of milk thistle to increase alcohol tolerance, although it is certainly being used for this purpose. The effectiveness of silymarin for viral hepatitis is not clear, although several trials demonstrated enough benefit to encourage further studies.
Intravenous silymarin has been demonstrated to lower mortality from Amanita mushroom poisonings, but this formulation is available only in Europe.Animal studies have demonstrated hepatic protection against alcohol, acetaminophen, and mushroom toxins and protection against hepatic fibrosis with bile duct occlusion. There is also evidence of silybin protecting against cisplatin- induced nephrotoxicity in rats. It is not yet clear whether milk thistle extract offers any renal protection to humans.

Side effects

Milk thistle appears to be remarkably safe, with loose stools due to increased bile solubility and occasional allergic reactions being the common side effects. It has not been evaluated in children or in pregnant women.There are no known serious drug or herb interactions.

Toxicity evaluation

Silymarin has been known for its very low toxicity, Acute toxicity studies of silymarin after intravenous infusion have been carried out in mice, rats, rabbits and dogs. The LD50 values were 400 mg/kg in mice, 385 mg/ kg in rats, and 140 mg/kg in rabbits and dogs though these values were dependent on infusion rate. With slow infusion rate (over 2 to 3 h) the LD50 increased to 2 g/kg in rats and after oral administration it was even 10 g/kg.

Silymarin(65666-07-1)Related Product Information

• (Trifluoromethoxy)benzene
• p-Anisidine
• Tris(hydroxymethyl)nitromethane
• 1,4-Dioxane
• 4-Methoxyphenylacetone
• CHLOROPHOSPHONAZO III
• Anisole
• p-Anisaldehyde
• POWDERED MILK THISTLE EXTRACT (250 MG)
• TRIS(2,2,6,6-TETRAMETHYL-3,5-HEPTANEDIONATO)EUROPIUM(III)
• SALCOMINE
• 2,4-PENTANEDIONE, SILVER DERIVATIVE
• DICHLORO(ETHYLENEDIAMINE)PLATINUM(II)
• Benzyl isocyanide
• TERT-BUTYL ISOCYANIDE
• PHENYLSELENOL
• Aluminum acetylacetonate
• Tris(2,4-pentanedionato)chroMiuM(III)
• Silybum Marianum