Pharmacology of silybum marianum and its active constituents. Therapeutic activity – part 1

Pharmacology of silybum marianum and its active constituents. Therapeutic activity – part 1

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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,
2011.
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,
2010.
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
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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: biologie@uvvg.ro

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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,
2011.
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,
2010.
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
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*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: biologie@uvvg.ro