Silybins

Fig. 2.50. Profiles of calendula (a), milk-thistle (b) and passion flower (c) tinctures (each 60 per cent v/v, ethanol) with the HPLC-MS attributions of the components detected, lc = quercetin-3-O-ruti-nosylrhamnoside 2c = rutin 3c = isorhamnetin-3-O-ruti-nosylrhamnoside 4c = isoquercitrin 5c = isorhamnetin-3-O-gluco-sylglucoside 6c = narcissin 7c = isorhamnetin-3-O-glucoside lm = taxifolin 2m = siliydianin 3m = silychristin 4m = oxy derivative of silybin/isosilybin isomers 5m and 6m = 2,3-dehydro derivatives of silybin/isosilybin isomers 7m = silybin 8m = isosilybin lp = 6,8-diC-glucosylapigenin 2p = isoschaftoside 3p = shaftoside 4p = homoorientin 5p = isovetexin-2"-0-glucoside 6p = vitexin. Reprinted with permission from A. R. Biha et al. [150].

Silybin (119) Flavonolignoid IdB 1016 (Silipide Silybin and phosphatidylcholine complex Silophos ) Oncology Antioxidant and anti-inflammatory Phase II (cancer chemo-prevention) American College of Gastroenterology/ Indena 714-719... 

Provinciali M, Papalini F, Orlando F, Pierpaoli S, Donnini A, Morazzoni P, Riva A, Smorlesi A. (2007) Effect of the silybin-phosphatidylcholine complex (IdB 1016) on the development of mammary tumors in HER-2/neu transgenic mice. Cancer Res 67 2022-2029. 

Gazak R, Walterova D, Kren V. (2007) Silybin and silymarin — new and emerging applications in medicine. CurrMed Chem 14 315-338. 

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 cis-platin-induced nephrotoxicity in rats. It is not yet clear whether milk thistle extract offers any renal protection to humans. 

Maitrejean, M. et al.. The flavanolignan silybin and its hemisynthetic derivatives, a novel series of potential modulators of P-glycoprotein, Bioorg. Med. Chem., 10, 1, 1999. 

Silymarin is considered the active constituent of the milk thistle seed, but it is not a single compound but a descriptive term for several flavonoli-gnans. Constituent analysis of five milk thistle products identified six constituents (representative amount) taxifolin (3.3%), silichristin (23.6 /o), silidianin (5.3 /o), silybin A (20%i), silybin B (30.7%i), and isosilybin (17.3 /o). The total amounts of silybin A and B in the five different products analyzed ranged from 45.7 /o to 61%i. The biological effect of each constituent is not known hence, spectrophotometric analysis would not provide sufficient information for a critical comparison of these products. 

Milk thistle (Silybum marianum) is an annual to biennial plant of the Aster-aceae family. It is native principally to southern Europe and northern Africa. The crude drug consists of the ripe fruits from which the pappus has been removed. Milk thistle fruits contain 15% to 30% proteins. The main active compounds constitute only about 2% to 3% of the dried fruits. The active principle is a mixture of flavolignans called silymarin. Silymarin, a polyphenolic extract isolated from the seeds of milk thistle, is composed mainly of silybin (50 70%), with small amounts of other silybin structural isomers, namely isosilybin, silydianin, and silychristin (Fig. 11) (123-125). The highest concentration of silymarin is found in the ripe fruits (126). Silibinin is the main compound, also considered to be the most active one in several paradigms (127). 

Compound silybin silybin Total silybin Unconjugated silybin ... 

After administration of silipide (lipophilic silybin-phosphatidylcholine complex) containing 80 mg equivalent silibinin. 

Chasseaud LF. Zur biologischen Verfuegbarkeit und Verstoffwechselung von Silybin. Dtsch Apoth Ztg 1975 115 1205-1206. 

Koch H, Zinsberger G. Loeslichkeitsparameter von Silybin, Silydianin und Silychristin. Arch Pharm 1980 313 526-533. 

Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E. Pharmacokinetic studies on IdB 1016, a silybin-phosphatidylcholine complex, in healthy human subjects. Eur J Drug Metab Pharmacokinet 1990 15 333-338. 

Gatti G, Perucca E. Plasma concentrations of free and conjugated silybin after oral intake of a silybin-phosphatidyl complex (silipide) in healthy volunteers. Int J Clin Pharmacol Ther 1994 30 134-138. 

Schandalik R, Gatti G, Perucca E. Pharmacokinetics of silybin in bile following administration of silipide and silymarin in cholecystectomy patients. Arzneim Eorsch/Drug Res 1992 42 664—668. 

Orlando R, Eragasso A, Lampertico M, et al. Pharmacokinetic study of silybin-phosphatidylcholin complex in liver cirrhosis after multiple doses. Med Sci Res 1990 19 827-828. 

The fruit and seeds of the milk thistle plant contain a lipophilic mixture of flavonolignans known as silymarin. Silymarin comprises 2-3% of the dried herb and is composed of three primary isomers, silybin (also known as silybinin or silibinin), silychristin (silichristin), and silydianin (silidianin). Silybin is the most prevalent and potent of the three isomers and accounts for about 50% of the silymarin complex. Products should be standardized to contain 70-80% silymarin. 

Although milk thistle has not been confirmed as an antidote following acute exposure to liver toxins in humans, parenteral silybin is nevertheless marketed and used in Europe as an antidote in Amanita phalloides mushroom poisoning. This use is based on favorable outcomes reported in case-control studies. 

There are no reported drug-drug interactions or precautions for milk thistle. Recommended dosage is 280-420 mg/d, calculated as silybin, in three divided doses. 

Silybum marianum (L.) Gaertn. Shui Fei Ji (fruit) Silybin, silymarin, silydiamin, silyckristin, dehydrosilybin, silybinomer.33 Maintain normal functioning of the liver, promote the regeneration of injured hepatic cells, increase glycogenesis and nucleic acid metabolism. 

Benzodioxanes (6, 516). The earlier synthesis of benzodioxanes by oxidative coupling of catechol derivatives with methoxypropenylphenols has been extended to the first synthesis of the complex benzodioxane silybin (3) shown in equation (I).2 The starting materials are (2R,3R)-dihydroqucrcctin (I) and coniferyl alcohol (2). In this case, the reaction is not regioselective, 3 and the isomeric 4 being obtained in nearly equal amounts. 

---