Copyright ©2011 Baishideng Publishing Group Co.
World J Gastroenterol. May 14, 2011; 17(18): 2288-2301
Published online May 14, 2011. doi: 10.3748/wjg.v17.i18.2288
Table 1 Pharmacokinetics of silybin phytosome and silymarin in healthy participants[38-43]
Silybin phytosomeSilymarin
Peak concentration (ng/mL)298 ± 96102 ± 22a
Time of peak (h)1.6 ± 0.31.4 ± 0.3
Mean residence time (h)3.6 ± 0.43.5 ± 0.4
AUC (ng/mL/h)881 ± 207257 ± 66b
Table 2 Pharmacokinetics of silybin after administration to 12 healthy volunteers as silymarin or silybin-phosphatidylcholine-vitamine E complex (RA)[43]
ProductCmax (ng/mL)Tmax(h)AUC (ng/mL per hour)
RA granules (47 mg silybin)213 ± 1660.5246 ± 114
RA capsules (47 mg silybin)117 ± 931.0161 ± 85
Silymarin gran (58 mg silybin)18 ± 170.525 ± 18
Silymarin caps (80 mg silybin)5 ± 71.011 ± 5
Table 3 Comparison between silybin phytosome and silymarin pharmacokinetics in patients with liver cirrhosis[44]
Silybin phytosomeSilymarin
(360 mg)(336 mg)
Cmax (ng/mL)860 ± 166b83 ± 15
Tmax (h)2.7 ± 0.7b2.6 ± 2.1
/2 (h)3.3 ± 0.7b2.6 ± 0.4
AUC515 ± 665b262 ± 39
Total bioavailability252 ± 39b19 ± 23
Table 4 Interference of silybin with cytochromes[48-64]
InterferencePossible interferenceNo interference
Table 5 Antioxidant effects of silybin[65-75]
From 10 to 100 μmol/LHepatocytesDecreased formation of reactive oxygen species from mitochondria; iron chelator
HepG2Decreased formation of superoxide anion
Mean dose with documented effects: 20 μmol/LKupffer cellsDecrease of NO production
MonocytesScavenger of lipodienyl, methyl, trichloromethyl radicals
Endothelial cellsDecrease of hydrogen peroxide concentration
Cancer cellsBlock of membrane lipid peroxidation
Table 6 Anti-inflammatory/antifibrotic effects of silybin[79-99]
From 5 to 50 μmol/LHepatocytesInhibition of NF-κB-mediated signaling
Mean: 15 μmol/LEndothelial cellsSuppression of IκBα phosphorylation
PlateletsInhibition of protein kinase kinase
Cancer cellsInhibition of c-jun N-terminal kinase
PhagocytesInhibition of leukotriene formation
Stellate cellsInhibition of release of cytochrome c
HepG2Inhibition of ERK, MEK, and Raf phosphorylation; inhibition of release of caspase 9 and 3, IL-8, and of PDGF- and TGF-β-mediated signaling; decrease of MMP2; increase of TIMP2; inhibition of HCV replication
Table 7 Effects of silybin on hepatic metabolism of glucose at doses of 25-100 μmol/L in hepatocytes[100-102]
25-100 μmol/LHepatocytesInhibition of pyruvate kinase
Inhibition of glycolytic flux
Inhibition of glucose-6-phosphate hydrolysis
Inhibition of glucose-6-phosphatase
Table 8 Other effects of silybin on cellular signaling[106-122]
Induction of apoptosis through an inhibition of IGF-IR
Down regulation of survivin and an increase in p53 expression
Block of cycle-regulator cyclins and promoter activities
Decrease of MMP-1 production
Decrease of angiogenesis
Inhibition of VEGF expression
Inhibition of HIF-1α
Increase of IGFBP-3
Table 9 Main studies performed by using purified silybin as drug
AuthorsType of study, number of patientsDrug used, dose and duration of treatmentsOutcomesResultsClinical relevance
Vailati et al[146]A phase II randomised, open trial on 60 patients with chronic alcoholic or viral hepatitisThree doses (160, 240, 360 mg) of silybin and phosphatidylcholine (IdB 1016, Indena, Italy) for two weeks. No placebo or no intervention group was usedLiver testsImprovement of liver enzymes with all used dosesScarce
Buzzelli et al[147]Double blind with identical placebo. Twenty patients with HBV and/or HCV chronic active hepatitisIdB1016 (complex with phosphatidylcholine and silybin) two capsules, twice a day (equivalent to 120 mg of silybin in each capsule) (480 mg/d). Duration of treatment and of follow-up: two months in totalMortality. Liver biochemistryImprovement of liver enzymes and bilirubinScarce
Buzzelli et al[148]Unclear, described as double blind but the method to achieve this was not described. Trial characteristics: cross over design. Patients were assigned to the Silipide group for two months treatment, and one month washout. Ten patients with chronic hepatitis C. (non-responders) to a previous treatment with recombinant interferon αSilipide (IdB1016) capsules 360 mg/d. Control group: placebo capsules. Duration of treatment and follow-up: two months of treatment and one month of washoutMortality. Liver biochemistryResults were not reported separately, only overall results. Improvement of liver testsData published only in abstract form
Lirussi et al[104]Blinding: adequate, double blind with placebo of identical appearance. Sixty out-patients with chronic alcoholic liver disease and non-insulin dependent type 2 diabetesSilybin-β-cyclodextrin (135 mg silybin) sachets t.i.d Duration of treatment: 6 moMortality. Liver biochemistryDecrease of fasting glucose and lipid peroxidation markersGood
Bares et al[138]Randomized study to 1 of 3 oral doses. Thirthy seven patients with chronic hepatitis C non responders to a previous IFN treatmentIdB1016 at 314, 628, 942 mg t.i.d.(120,240 and 360 mg t.i.d. silybin equivalents, respectively) for 12 wkEffects on serum markers of iron statusThere was a significant decrease in serum ferritin, that was independently associated with the stage III-IV of liver fibrosiGood
Falasca et al[134]Observational study on forthy naïve HCV positive patients (30 treated and 10 observed without treatments)Silybin-Vitamine E-Phospholipid Complex (Realsil®- Ibi-Lorenzini-Italy) in a dose of 4 pills per day (each pill: 47 mg of silybin) for 3 moHepatoprotection and anti-inflammatory effect by determining cytokine pattern and markers of liver diseaseImprovement of liver enzymes and of Il2 plasma levels. Improvement of insulin resistance markers in patients with contemporaneous liver steatosisMedium
Federico et al[141]Observational study on 85 outpatients: 59 with NAFLD and 26 with HCV related chronic hepatitis in combination with NAFLD, non-responders to previous antiviral treatment. 53 (39 NAFLD and 14 HCV) were treated, while the other 32 patients (20 NAFLD and 12 HCV) served as a control group (no treatment)The complex silybin-vitamin E-phospholipids (Realsil®), 4 pieces/d for six months followed by another six months of follow upEffects on insulin resistance and liver damageUS steatosis, liver enzymes, hyperinsulinaemia, and indices of liver fibrosis were improved in both treated groupsSuggestive
Ferenci et al[139]Observational study on 36 patients with HCV chronic hepatitis non responders to IFN + ribavirin. Duration of the study: 7 dSilybin i.v. (Madaus, Germany) at 5, 10, 15 and 20 mg/kg per day for 14 dEffect on viral load. SafetyGood compliance, no side effects and potent antiviral effect against HCVHigh