Silybin is a flavin oligosaccharide extracted from Silybum marianum seeds. Silybin causes apoptosis and has hepatoprotective, antioxidant, anti-inflammatory, and anti-cancer activities.

Physicochemical Properties

Molecular Formula	C25H22O10
Molecular Weight	482.44
Exact Mass	482.121
CAS #	802918-57-6
Related CAS #	Silybin A;22888-70-6;Isosilybin;72581-71-6;Silybin B;142797-34-0
PubChem CID	31553
Appearance	White to off-white solid powder
Melting Point	152-153°C
LogP	2.362
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	4
Heavy Atom Count	35
Complexity	750
Defined Atom Stereocenter Count	4
SMILES	COC1=C(C=CC(=C1)[C@@H]2[C@H](OC3=C(O2)C=C(C=C3)[C@@H]4[C@H](C(=O)C5=C(C=C(C=C5O4)O)O)O)CO)O
InChi Key	SEBFKMXJBCUCAI-HKTJVKLFSA-N
InChi Code	InChI=1S/C25H22O10/c1-32-17-6-11(2-4-14(17)28)24-20(10-26)33-16-5-3-12(7-18(16)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/t20-,23+,24-,25-/m1/s1
Chemical Name	(2R,3R)-3,5,7-trihydroxy-2-[(2R,3R)-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2,3-dihydrochromen-4-one
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Growth inhibition is time-and dose-dependent for silybin (0-200 mM; for 72 hours)[1]. Silybin (68 μM; for 72 hours) causes apoptosis and raises the percentage of cells in the G1 phase to about 22% [1]. AKT activity inhibition is induced by silybin (68 μM) for a duration of 72 hours[1].
ln Vivo	For the last four weeks, silybin (50–100 mg/kg/day; administered intragastrically) has been shown to dramatically reduce hepatic and serum lipid accumulation[2].
Cell Assay	Cell Viability Assay[1] Cell Types: HepG2 cell growth Tested Concentrations: 0-200 mM Incubation Duration: For 72 hrs (hours) Experimental Results: Had growth inhibition in a time- and dose-dependent manner with an IC50 of 68 μM. Apoptosis Analysis[1] Cell Types: HepG2 cell growth Tested Concentrations: 68 μM Incubation Duration: For 72 hrs (hours) Experimental Results: Induced apoptosis in a higher number of cells (60%) when compared to untreated cells. Cell Cycle Analysis[1] Cell Types: HepG2 cell growth Tested Concentrations: 68 μM Incubation Duration: For 72 hrs (hours) Experimental Results: Increased the cells in G1-phase of ~22% and diminished of 47% the cells in S-phase. Western Blot Analysis[1] Cell Types: HepG2 cell growth Tested Concentrations: 68 μM Incubation Duration: For 72 hrs (hours) Experimental Results: Induced AKT activity inhibition.
Animal Protocol	Animal/Disease Models: Male C57BL/6J mice (6-8 weeks old) with nonalcoholic fatty liver disease (NAFLD)[2] Doses: 50, 100 mg/kg Route of Administration: Given intragastrically (po); daily; for the last 4 weeks Experimental Results: Dramatically lowered both serum and hepatic lipid accumulation.
ADME/Pharmacokinetics	Metabolism / Metabolites Silybin has known human metabolites that include O-demethylated-silybin.
References	[1]. Silybin-Induced Apoptosis Occurs in Parallel to the Increase of Ceramides Synthesis and miRNAs Secretion in Human Hepatocarcinoma Cells. Int J Mol Sci. 2019 May 3;20(9):2190. [2]. Silybin ameliorates hepatic lipid accumulation and modulates global metabolism in an NAFLD mouse model. Biomed Pharmacother. 2020 Mar;123:109721.
Additional Infomation	Silibinin is a flavonolignan isolated from milk thistle, Silybum marianum, that has been shown to exhibit antioxidant and antineoplastic activities. It has a role as an antioxidant, an antineoplastic agent, a hepatoprotective agent and a plant metabolite. It is a flavonolignan, a polyphenol, an aromatic ether, a benzodioxine and a secondary alpha-hydroxy ketone. Silibinin is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silicristin, silidianin and others. Silibinin is presented as a mixture of two diastereomers, silybin A and silybin B, which are found in an approximately equimolar ratio. Both in vitro and animal research suggest that silibinin has hepatoprotective (antihepatotoxic) properties that protect liver cells against toxins. Silibinin has also demonstrated in vitro anti-cancer effects against human prostate adenocarcinoma cells, estrogen-dependent and -independent human breast carcinoma cells, human ectocervical carcinoma cells, human colon cancer cells, and both small and nonsmall human lung carcinoma cells. Silibinin has been reported in Aspergillus iizukae, Silybum eburneum, and other organisms with data available. Silymarin is a mixture of flavonolignans isolated from the milk thistle plant Silybum marianum. Silymarin may act as an antioxidant, protecting hepatic cells from chemotherapy-related free radical damage. This agent may also promote the growth of new hepatic cells. (NCI04) The major active component of silymarin flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum; it is used in the treatment of HEPATITIS; LIVER CIRRHOSIS; and CHEMICAL AND DRUG INDUCED LIVER INJURY, and has antineoplastic activity; silybins A and B are diastereomers. Drug Indication Currently being tested as a treatment of severe intoxications with hepatotoxic substances, such as death cap (Amanita phalloides) poisoning.

Solubility Data

Solubility (In Vitro)

DMSO : 25 mg/mL (51.82 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0728 mL	10.3640 mL	20.7280 mL
	5 mM	0.4146 mL	2.0728 mL	4.1456 mL
	10 mM	0.2073 mL	1.0364 mL	2.0728 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.