Journal Info

Title: Jurnal Medical Aradean (Arad Medical Journal)
Abbreviated title: J. Med. Ar.
Publisher: "Vasile Goldis" University Press
Owner: Western University "Vasile Goldis" Arad, Romania
ISSN: 1224-3744
e-ISSN: 2067-7790

Ranking and Indexing

Rank: CNCSIS C (code 292) since 2010

International Database: Index Copernicus Journal Master List Value (2010): 4.66

Who's Online

We have 22 guests online

Index Databases

Pharmacology of silybum marianum and its active constituents. Therapeutic activity – part 1 PDF Print E-mail
Written by Pilat L., Mihali C., Herman H., Popescu C., Turcus V., Ardelean A., Ardelean G., Mariasiu T., Popa C., Hermenean A.   
Read full article
Article Title: Pharmacology of silybum marianum and its active constituents. Therapeutic activity – part 1
Authors: Luminita Pilat1, Ciprian Mihali2, Hildegard Herman2, Cristina Popescu2, Violeta Turcus3, Aurel
Ardelean3, Ardelean Gavril3, Teodora Mariasiu1, Calin Popa1, Anca Hermenean1,2*
Affiliation: 1“Vasile Goldis” Western University of Arad, Faculty of Medicine, Pharmacy and Dentistry, Arad, Romania
2“Vasile Goldis” Western University of Arad, Institute of Life Sciences, Arad, Romania
3“Vasile Goldis” Western University of Arad, Faculty of Natural Sciences, Arad, Romania
Abstract: In the last years a lot of effort has been made in demonstrating the role of plant extracts in medicine. The usage
of herbal drugs for the treatment of several diseases has increased all over the world. The global popularity of
herbal supplements and the promise they hold in treating various disease states has caused an unprecedented
interest in understanding the molecular basis of the biological activity of traditional remedies. The herbal drugs
are believed to be harmless without causing adverse reactions, as they are obtained from nature and are
easily available. There are about 600 commercial herbal formulations available only for liver disease, which are
claimed to have hepatoprotective effects. As the need for effective, affordable health promotion and treatment
increases, especially in the growing ageing population, there is a need for rigorous scientific examination of
herbal medicines. This article reviews on published reports pertaining to milk thistle’s benefits.
Keywords: Silymarin, disease, pharmacokinetics, regeneration, herbal medicine
References: Al-Anati L, Essid E, Reinehr R, Petzinger E, Silibinin
protects OTA-mediated TNF-a release from
perfused rat livers and isolated rat Kupffer cells.
Mol.Nutr.Res., 53, 460-466, 2009.
Avizeh R, Najafzadeh H, Razijalali M, Shirali S,
Evaluation of prophylactic and therapeutic effects of
silymarin and N-acetylcysteine in acetaminopheninduced
hepatotoxicity in cats. J.Vet.Pharmacol.
Therap., 33, 95-99, 2009.
Basiglio C, Pozzi EJS, Mottino AD, Roma MG,
Differential effects of silymarin and its active
component silibinin on plasma membrane stability
and hepatocellular lysis. Chemico-Biological
Interactions, 179, 297-303, 2009.
Brandon-Warner E, Sugg JA, Schrum LW, Mckillop LH,
Silibinin inhibits ethanol metabolism and ethanoldependent
cell proliferation in an vitro model of
hepatocellular carcinoma. Cancer Letters, 291, 120-
129, 2010.
Carpino G, Morini S, Gianinni Corradini S et al,
Alpha_SMA expression in hepatic stellate cells and
quantitative analysis of liver fibrosis in cirrhosis
and in recurrent chronic hepatitis after liver
transplantation, Dig.Liver Dis., 37, 349-356, 2005.
Chang HR, Chen PN, Yang SF, Sun YS, Wu SW, Hung
TW, Lian JD, Chu SC, Hsieh YS, Silibinin inhibits
the invasion and migration of renal carcinoma 786-o
cells in vitro, inhibits the growth of xenografts in vivo
and enhances chemosensitivity to 5-fluorouracil and
paclitaxel. Molecular Carcinogenesis, 50, 812–823,
Chen CH, Huang TS, Wongc CH, Hong CL, Tsai YH,
Liang CC, Lu FJ, Chang WH, Synergistic anticancer
effect of baicalein and silymarin on human
hepatoma HepG2 Cells. Food and Chemical
Toxicology, 47, 638–644, 2009.
Cho YK, Yun JW, Park JH, Kim HJ, Park DII, Sohn CII,
Jeon WK, Kim BI, Jin W, Kwon YH, Shin MK, Yoo
TM, Kang JH, Park CS, Sohn CI, Jeon WK, Kim
BI, Jin W, Kwon YH, Shin MK, Yoo TM, Kang JH,
Park CS, Deleterious effects of silymarin on the
expression of genes controlling endothelial nitric
oxide synthase activity in carbon tetrachloridetreated
rat livers. Life Sciences, 85, 281-290, 2009.
Colombo V, Lupi M, Falcetta F, Forestieri D, D’Incalci
M, Ubezio P, Chemotherapeutic activity of silymarin
combined with doxorubicin or paclitaxel in sensitive
and multidrug-resistant colon cancer cells. Cancer
Chemother Pharmacol, 67, 369–379, 2011.
Colturato CP, Constantin RP, Maeda Jr. AS, Constantin
RP, Yamamoto NS, Bracht A, Ishii-Iwamoto EL,
Constantin J, Chemico-Biological Interactions, 195,
119–132, 2012.
Crocenzi FA et al, Silibinin [Milk thistle] prevents
cholestasis-associated retrieval of the bile salt
export pump, Bsep, in isolated rat hepatocyte
couplets: possible involvement of camp. Biochem
Pharmacol., 69(7), 1113-20, 2005.
Crocenzi FA, Sanchez-Pozzi EJ, Pellegrino JM, et al.
Beneficial effects of silymarin on estrogen-induced
cholestasis in the rat: A study in in vivo and in
isolated hepatocyte couplets. Hepatology, 34, 329–
339, 2001.
Das S, Roy P, Auddy RG, Mukherjee A, Silymarin
nanoparticle prevents paracetamol-induced
hepatotoxicity, International Journal of
Nanomedicine, 6, 1291–1301, 2011.
De La Puerta R, Martinez E, Bravo L. Effect of silymarin
on different acute inflammation models and on
leukocyte migration. J Pharm Pharmacol, 48, 968-
970, 1996.
Deep G, Agarwal R, Antimetstatic efficacy of silibinin:
molecular mechanisms and therapeutic potential
against cancer. Cancer Metastasis Rev, 29, 447-463,
Deep G, Oberlies NH, Kroll DJ, Agarwal R, Identifying
the differential effects of silymarin constituents on
cell growth and cell cycle regulatory molecules in
human prostate cancer cells. Int. J. Cancer:, 123,
41–50, 2008.
Dehmlow C, Erhard J, de Groot H. Inhibition of
Kupffer cell functions as an explanation for the
hepatoprotective properties of silibinin. Hepatology,
23, 749-754, 1996.
Dehmlow C, Inhibition of Kupffer cell functions as an
explanation for the hepatoprotective properties of
silibinin. Hepatology, Apr; 23 (4): 749-54, 1996.
Doehmer J, Weiss G, Weiss GP, Mc Gregor GP, Appel
K, Assessment of a dry extract from milk thistle
(Silybum marianum) for interference with human
liver cytochrome P450 activities. Toxicology in
vitro, 25, 21-27, 2011.
Duan WJ, Li QS, Xia MY, Tashiro SI, Onodera S, Ikejima
T, Silibinin activated p53 and induced autophagic
death in human fibrosarcoma ht1080 cells via
reactive oxygen species-p38 and c-jun n-terminal
kinase pathways. Biol. Pharm. Bull., 34(1), 47—53,
Erlejman AG, Verstraeten SV, Fraga CG, Oteiza PI, The
interaction of flavonoids with membranes: potential
determinant of flavonoid antioxidant effects. Free
Radic.Res, 38, 1311-1320, 2004
Esmaily H, Hosseini-Tabatabaei A, Rahimian R,
Khorasani R, Baeeri M, Barazesh-Morgani A, Yasa
N, Khademi Y, Abdollahi M, On the benefits of
silymarin in murine colitits by improving balance of
destructive cytokines and reduction of toxic stress
in the bowel cells. Centr.Eur.J.Bio., 4(2), 204-213,
Esmaily H, Vaziri-Bami A, Miroliaee AE, Baeeri M,
Abdollahi M, The correlation between NH-kb
inhibition and disease activity by coadministration of
silibinin and ursodeoxycholic acid in experimental
colitis. Fundamental&Clinical Pharmacology, 25,
723-733, 2010.
Fantozzi R, Brunelleschi S, Rubino A, et al. FMLPactivated
neutrophils evoke histamine release from
mast cells. Agents Actions, 18:155-158, 1986.
Flaig TW, Glode M, Gustafson D, van Bokhoven A,
Tao Y, Wilson S, Su LJ, Li Y, Harrison G, Agarwal
R, Crawford ED, Lucia MS, Pollak M, A study
of high-dose oral silybin-phytosome followed by
prostatectomy in patients with localized prostate
cancer. The Prostate 70, 848-855, 2010
Girish C, Koner BC, Jayanthi S, Rao KR, Rajesh B,
Pradhan SC, Hepatoprotective activity of picroliv,
cucurmin and ellagic acid compared to silymarin
on paracetamol induced liver toxicity in mice.
Fundamental&Clinical Pharmacology, 23, 735-745,
Gopalakrishnan R., Sundaram J.,Sattu K.,Pandi
A.,Thiruvengadam D., (2009) Silymarin attenuated
mast cell recruitment thereby decreased the
expressions of matrix metalloproteinases-2 and 9
in rat liver carcinogenesis, Invest New Drugs, 27,
Haddad Y, Vallerand D, Brault A, Haddad PS, Antioxidant
and hepatoprotective effects of silibinin in a rat
model of nonalcoholic steatohepatitis. Evid. Based.
Complement. Alternat. Med. (Epub ahead of print),
Hui J.J., Park J.-W., Lee J.S., Lee S.-R., Jang B.-C., Suh S.-
I., Suh M.-H., Baek W.-K., (2009) Silibinin inhibits
expression of HIF-1α through suppression of protein
translation in prostate cancer cells, Biomedichal and
Biophysical Research Communications 390, 71-76.
Jain A, Yadav A, Bozhkov AI, Padalko VI, Flora SJS,
Therapeutic efficacy of sylimarin and naringenin in
reducing arsenic-induced hepatic damage in young
rats. Ecotoxicology and Environmental Safety, 74,
607-614, 2011.
Jeong JC, Shin WY, Kim TH, Kwon CH, Kim JH,
Kim YK, Kim KH, Silibinin induces apoptosis
via calpain-dependent AIF nuclear translocation
in U87MG human glioma cell death. Journal of
Experimental & Clinical Cancer Research, 30, 44,
1-8, 2011.
Jiang YY, Huang H, Wang H, Wu D, Yang R, Tashiro S,
Onodera S, Ikejima T, Interruption of mitochondrial
complex IV activity and cytochrome c expression
activated O2-mediated cell survival in silibinintreated
human melanoma A375-S2 cells via IGF-
1R–PI3K–Akt and IGF-1R–PLC γ–PKC pathways.
European Journal of Pharmacology, 668, 78–87,
Jiang YY, Wang H, Wang J, Tashiro SI, Onodera S,
Ikejima T, The Protective Effect of Silibinin Against
Mitomycin C–Induced Intrinsic Apoptosis in Human Melanoma A375-S2 Cells. J. Pharmacol.
Sci., 111, 137–146, 2009.
Kauntz H, Bousserouel S, Gosse F, Raul F, Silibinin
triggers apoptotic signaling pathways and autophagic
survival response in human colon adenocarcinoma
cells and their derived metastatic cells. Apoptosis,
16, 1042–1053, 2011.
Kim KW, Choi CH, Kim TH, Kwon CH, Woo JS, Kim
YK, Silibinin inhibits glioma cell proliferation via
ca2+/ros/mapk dependent mechanism in vitro and
glioma tumor growth in vivo. Neurochem Res, 34,
1479–1490, 2009.
Kim S, Kim SH, Hur SM, Lee SK, Kim WW, Kim
JS, Kim JH, Choe JH, Nam SJ, Lee JE, Yang JH,
Silibinin prevents TPA-induced MMP-9 expression
by down-regulation of COX-2 in human breast
cancer cells. Journal of Ethnopharmacology, 126,
252–257, 2009.
Koch HP, Silymarin [Silybum marianum]: potent inhibitor
of cyclic AMP phosphodiesterase. Methods Find
Exp Clin Pharmacol. Aug;7(8), 409-13, 1985.
Kropacova K, Misurova E, Hakova H, Protective and
therapeutic effect of silymarin on the development
of latent liver damage. Radiats Biol Radioecol, 38,
411-415, 1998.
Lieber CS, Leo MA, Cao Q, Ren C, DeCarli LM,
Silymarin retards the progression of alcohol-induced
hepatic fibrosis in baboons. J. Clin. Gastroenterol.,
37, 336–339, 2003.
Machicao F, Sonnenbichler J, Mechanism of the
stimulation of RNA synthesis in rat liver nuclei by
silybin, Hoppe Seylers Z.Physiol.Chem, 358, 141-
147, 1997.
Mateen S, Tyagi A, Agarwal C, Singh RP, Agarwal R,
Silibinin inhibits human nonsmall cell lung cancer
cell growth through cell-cycle arrest by modulating
expression and function of key cell-cycle regulators.
Molecular Carcinogenesis, 49(3), 247–258, 2010.
Mcpartland JM, Viral hepatitis treated with Phyllanthus
amarus and milk thistle (Silybum marianum): A
case report. Complementary Medicine International,
March/April, 40- 42, 1996.
Mohamed O, Salam EA, Saleem AA, Shafee N,
Hepatoprotective effects of the nitric oxide donor
isosorbide-5-mononitrate alone and in combination
with the natural hepatoprotectant, silymarin on
carbon tetrachloride-induced hepatic injury in rats.
Inflammopharmacol, 18, 87-94, 2010.
Nassuato G, Iemmolo RM, Strazzabosco M, Lirussi F,
Deana R, Francesconi MA, Muraca M, Passera D,
Fragosso A, Orlando R, Csomós G, Okolicsányi
L, Effect of Silibinin on biliary composition.
Experimental and clinical study. J. Hepatol., 12,
290–295, 1991.3
Nouchi T, Tanaka Y, Tsukada T et al, Appearance of
alpha-smooth-muscle-actin-positive cells in hepatic
fibrosis. Liver, 11, 100-105, 1991.
Park JH, Park JH, Hur HJ, Woo SJ, Lee HJ, Effects of
silymarin and formulation on the oral bioavailability
of paclitaxel in rats. European Journal of
Pharmaceutical Sciences, 45, 296-301, 2012.
Passera D, Fragasso A, Orlando R, et al. Effect of
silybinin on biliary lipid composition: Experimental
and clinical study. J Hepatol, 12, 290–295, 1991.
Pietrangelo A, Borella F, Casalgrandi G, Antioxidant
activity of silybin in vivo during long-term iron
overload in rats. Gastroenterology, 109, 1941-1949,
Ramakrishnan G, Muzio LL, Elinos-Baez CM, Jagan
S, Augustine TA, Kamaraj S, Devaki T, Silymarin
inhibited proliferation and induced apoptosis in
hepatic cancer cells. Cell Prolif, 42, 229-240, 2008.
Ramasamy K., Dwyer-Nield L. D., Serkova N. J.,
Hasebroock K. M., Tyagi A., Raina K., Singh R.P.,
Malkinson A. M., Agarwal R., (2010) Silibinin
Prevents Lung Tumorigenesis in Wild-Type but not
in iNOS-/- Mice: Potential of Real-Time Micro-CT
in Lung Cancer Chemoprevention Studies, Clinical
Cancer Research, March 1, 753-761.
Rho JK, Choi YJ, Jeon BS, Choi SJ, Cheon GJ, Woo SK,
Kim HR, Kim CH, Choi CM, Lee JC, Combined
treatment with silibinin and epidermal growth factor
receptor tyrosine kinase inhibitors overcomes drug
resistance caused by t790m mutation. Molecular
Cancer Therapeutics, March 1, 3233- 3243, 2012.
Sangeetha N., Aranganathan S., Panneerselvam J., Shanthi
P., Rama G., Nalini N., (2010) Oral supplementation
of silibinin prevents colon carcinogenesis in a
long term preclinical model, European Journal of
Pharmacology 643, 93–100.
Schriewer H, Weinhold F, The influence of silybin
from Silybum marianum (L.) Gaertn. On in vitro
phosphatidyl choline biosynthesis in rat livers.
Arzneimittelforschung, 29, 791–792, 1979.
Schumann J, Prockl J, Kiemer AK, Vollmar AM, Silibinin
protects mice from T cell-dependent liver injury. J.
Hepatol., 39, 333-340, 2003.
Shafik AN, Khodeir MM, Gouda NA, Mahmoud ME,
Improved antifibrotic effect of a combination
of verapamil and silymarin in rat –induced liver
fibrosis. Arab Journal of Gastroenterology, 12, 143–
149, 2011.
Shaker ME, Shiha GE, Ibrahim TM, Comparison of
early treatment with low doses of nilotinib, imatinib
and a clinically relevant dose of silymarin in thioacetamide–induced liver fibrosis. European
Journal of Pharmacology, 670, 593-600, 2011.
Sonnenbichler J, Goldberg M, Hane I, et al., Stimulating
effects of silibinin on the DNA-synthesis in partially
hepatectomized rat livers: non-response in hepatoma
and other malignant cell lines. Biochem Pharmacol,
35, 538-541, 1986.
Sonnenbichler J, Zetl I, Biochemical effects of the
flavolignane silibinin on RNA, protein and DNA
synthesis in rat livers. In: Cody V, Middleton E,
and Harbourne JB, ed. Plant Flavonoids in Biology
and Medicine: Bio- chemical, Pharmacological, and
Structure- Activity relationships. New York: Alan
R. List, Inc.; 319-331, 1986.
Sonnenbichler J, Zetl I. Stimulating influence of a
flavonolignan derivative on proliferation, RNA
syn- thesis and protein synthesis in liver cells.
In: Okolocsanyi L, Csomos G, Crepaldi G, eds.
Assessment and Management of Hepatobiliary
Disease. Berlin: Springer-Verlag, 265-272, 1987.
Soria EA., Eynard AR, Bongiovanni GA, Cytoprotective
effects of silymarin on epithelial cells against
arsenic-induced apoptosis in contrast with quercetin
cytotoxicity, Life Sciences, 87, 309–315, 2010.
Tanamly MD, Tadros F, Labeeb S, Makld H, Shehata
M, Mikhail N, Abdel-Hamid M, Abu-Baki L,
Medhat A, Magder LS, Afdhal NH, Strickland
GT, Randomised, double-blinded trial evaluating
silymarin [Silybum marianum] for chronic hepatitis
C in an Egyptian village: study description and
12-month results. Dig Liver Dis., Nov, 36(11), 752-
9, 2004.
Tsai JH, Liu JY, Wu TT, Ho PC, Huang CY, Shyu JC,
Hsieh YS, Tsai CC, Liu YC, Effects of sylimarin on
the resolution of liver fibrosis induced by carbon
tetrachloride in rats. Journal od Viral Hepatitis, 15,
508-514, 2008.
Tyagi A, Sharma Y, Agarwal C, Agarwal R, Silibinin
impairs constitutively active TGFα-EGFR autocrine
loop in advanced human prostate carcinoma cells.
Pharmaceutical Research, Vol. 25, No. 9, 2143-
2149, 2008.
Upadhyay G, Tiwari MN, Praksh O, Jyoti A, Involvement
of multiple molecular events in pyrogallol-induced
hepatotoxicity and silymarin-mediated protection:
Evidence from gene expression profiles. Food and
Chemical Toxicology, vol.48, 1660-1670, 2010.
Vaid M, Prasad R, Sun Q, Katiyar SK, Silymarin Targets
b-Catenin Signaling in Blocking Migration/Invasion
of Human Melanoma Cells. PLoS ONE, Volume 6,
Issue 7, e23000, 2011
Velmurugan B, Gangar SC, Kaur M, Tyagi A, Deep
G, Agarwal R, Silibinin exerts sustained growth
suppressive effect against human colon carcinoma
SW480 xenograft by targeting multiple signaling
molecules. Pharm Res., 27, 2085–2097, 2010.
Verschoyle R. D., Brown K., Steward W.P., Gescher A.
J., (2008) Consumption of silibinin, a flavonolignan
from milk thistle, and mammary cancer development
in the C3(1) SV40 T,t antigen transgenic multiple
mammary adenocarcinoma (TAg) mouse, Cancer
Chemother Pharmacol, 62, 369–372.
Verschoyle RD, Greaves P, Patel K, Marsden DA, Brown
K, Steward WP, Gescher ASJ, Evaluation of the
cancer chemopreventive efficacy of silibinin in
genetic mouse models of prostate and intestinal
carcinogenesis. Relationship with silibinin levels.
European Journal of Cancer, 44, 898 –906, 2008
Wu CG, Chamuleau RA, Bosch KS, Protective effect of
silymarin on rat liver injury induced by ischemia.
Virchows Arch B Cell Pathol Incl Mol Pathol,
64:259-263, 1993
Wu DF, The effects of silymarin [Silybum marianum] on
hepatic microsomal and mitochondrial membrane
fluidity in mice. Zhongguo Zhong Yao Za Zhi,
28(9), 870-2, 2003.
Wu K, Zeng J, Zhu G, Zhang L, Zhang D, Li L, Fan J, Wang
X, He D, Silibinin inhibits prostate cancer invasion,
motility and migration by suppressing vimentin and
MMP-2 expression. Acta Pharmacologica Sinica,
30, 1162–1168, 2009.
Yadav NP, Pal A, Shanker K, Bawankule DU, Gupta
AK, Darokar MP, Khanuja PS, Synergistic effect of
sylimarin and standardized extract of Phyllanthus
amarus against CCl4-induced hepatotoxicity in
Rattus norvegicus, Phytomedicine, 15, 1053-1061,
Zhao H., Brandt G. E., Galam L., Matts R. L., Blagg B. S.
J., (2011) Identification and initial SAR of silybin:
An Hsp90 inhibitor, Biorganic and Medicinal
Chemistry Letters 21, 2659-2664.
Zhou L, Liu P, Chen B, Wang Y, Wan XG, Internati MC,
Wachtel MS, Eldo EF, Silibinin restores paclitaxel
sensitivity to paclitaxel-resistant human ovarian
carcinoma cells. Anticancer Research, 28, 1119-
1128, 2008.
*Correspondence: Anca Hermenean, “Vasile Goldis” Western University of Arad, Institute of Life Sciences, no. 86 Liviu Rebreanu St., 310414, Arad, Romania, Tel. +40257212111, Fax. +40257212111, email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it