Pharmacology of Silybum marianum and its active constituents. Therapeutic activity – part 2

Pharmacology of Silybum marianum and its active constituents. Therapeutic activity – part 2

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Article_Title: Pharmacology of Silybum marianum and its active constituents. Therapeutic activity – part 2
Authors: Hildegard Herman1, Luminita Pilat2, Ciprian Mihali1, Cristina Popescu1, Violeta Turcus3, Aurel
Ardelean3, Ardelean Gavril3, Teodora Mariasiu2, Calin Popa2, Anca Hermenean1,2*
Affiliation: 1“Vasile Goldis” Western University of Arad, Institute of Life Sciences, Arad, Romania
2“Vasile Goldis” Western University of Arad, Faculty of Medicine, Pharmacy and Dentistry, Arad, Romania
3“Vasile Goldis” Western University of Arad, Faculty of Natural Sciences, Arad, Romania
Abstract: Silymarin, a flavonolignan from ‘milk thistle’ (Sylibum marianum) plant is used from ancient times as a
hepatoprotective drug. Along the hepatoprotective action silymarin owns also other actions as antioxidant, antilipid
peroxidative, antifibrotic, anti-inflamatory, immunomodulatory, liver regenerating, etc. In Part 1 of this article
we reviewed the milk thistle’s benefic effects in gastrointestinal disorders and its antitumoral activities. Part 2
covers other applications of sylimarin such as antioxidant, antiinflamatory agent, nephroprotector, radiation and
skin protector. It was also studied its neuro-psihiatric and cardiac action.
Keywords: silymarin, oxidative stress, antioxidant, neuroprotection, T cell activation
References: Abbasi BH, Khan MA, Mahmood T, Ahmad M,
Chaudhary MF, Shoot regeneration and free-radical
scavenging activity in Silybum marianum L. Plant
Cell Tiss Organ Cult, 101, 371–376, 2010.
Ahmadi-Ashtiani H, Allameh A, Rastegar H, Soleimani
M, Barkhordari E, Inhibition of cyclooxygenase-2
and inducible nitric oxide synthase by silymarin in
proliferating mesenchymal stem cells: comparison
with glutathione modifiers. J Nat Med, 66, 85–94,
2012.
Altorjay I, Dalmi L, Sári B, Imre S, Balla G, The effect
of silibinin (Legalon) on the free radical scavenger
mechanisms of human erythrocytes in vitro, Acta
Physiol. Hung., 80, 375–380, 1992.
Au AY, Hasenwinkel JM, Frondoza CG, Silybin
inhibits interleukin-1b-induced production of
pro-inflammatory mediators in canine hepatocyte
cultures. J.Vet.Pharmacol.Therap, 34, 120-129,
2010.
Baluchnejadmojarad T, Neuroprotective effect of
silymarin in 6-hydroxydopamine hemi-parkinsonian
rat: Involvement of estrogen receptors and oxidative
stress. Neuroscience Letters, 480, 206-210, 2010.
Becker Schiebe M, Mengs U, Schafer M, Bulitta
M, Hoffman W, Topical use of sylimarin-based
preparation to prevent radiodermatitis. Stahlenther
Onkol., 8, 485-491, 2011.
Bosisio E, Benelli C, Pirola O, Effect of the flavanolignans
of Silybum marianum L. on lipid peroxidation in rat
liver microsomes and freshly isolated hepatocytes.
Pharmacol Res, 25, 147–54, 1992.
Chauhan V, Chauhan A, Oxidative stress in Alzheimer’s
disease. Pathophysiology, 13, 195–208, 2006.
Chtourou Y, Fetoui H, Sefi M, Trabelsi K, Barkallahm
M, Boudawara T, Kallei H, Zeghal N, Silymarin, a
natural antioxidant, protects cerebral cortex against
manganese-induced neurotoxicity in adult rats.
Biometals, 23, 985-996, 2010.
Fu H, Katsumura Y, Lin M, Hata K, Muroya Y, Hatano
Y, Fast Repair Activities Towards dgmp Hydroxyl
Radical Adducts by Silybin and its Analogues, J.
Radiat. Res., 49, 609–614, 2008.
Fu H, Lin M, Katsumura Y, Yokoya A, Hata K, Muroya
Y, Fujii K, Shikazono N, Protective effects of silybin
and analogues against X-ray radiation –induced
damage. Acta Biochim Sin, 42, 489-495, 2010.
Galhardi F, Mesquita K, Monserrat JM, Barros DM,
Effect of silymarin on biochemical parameters of
oxidative stress in aged and young rat brain, Food
and Chemical Toxicology, 47, 2655–2660, 2009.
Garagozloo M, Velardi E, Bruscoli S, Agostini M,
Sante MD, Donato V, Amirghofran Z, Riccardi
C, Silymarin suppress CD+T cell activation and
proliferation: Effects on NF-kB activity and IL-2
production. Pharmacological Research, 61, 405-
409, 2010.
Gažák R, Sedmera P, Vrbacký M, Vostálová J, Drahota
Z, Marhol P, Walterová D, Křen V, Molecular
mechanisms of silybin and 2,3-dehydrosilybin
antiradical activity—role of individual hydroxyl
groups. Free Radical Biology & Medicine 46, 745–
758, 2009.
Gazak R, Svobodova A, Psotova J, Sedmera P, Prikrylova
V, Walterova V, Kren V, Oxidised derivatives of
silybin and their antiradical and antioxidant activity.
Bioorg. Med. Chem. 12, 5677–5687, 2004.
Hou YC, Liou TK, Chern CM, Wang YH, Liao JF, Chang
S, Cho YH, Shen YC, Preventive effect of silymarin
in cerebral ischemia-reperfusion-induced brain
injury in rats possibly through impairing NF-kB and
STAT-1 activation. Phytomedicine, 17, 963-973,
2010.
Huang KX, Gong JX, Xiong W, Yang LX, Wang F,
Tao QF, Wu YH, Li XK, Stöckigt J, Zhao Y, Qu
J, Preparation of silybin 23-esters and evaluation
of their inhibitory ability against LPO and DNA
protective properties. Chinese Chemical Letters, 20,
1030–1033, 2009.
Huber A, Thongphasuk P, Erben G, Lehman WD, Tuma
S, Stremmel W, Chamulitrat W, Significantly
greater antioxidant anticancer activities of
2,3-dehydrosilybin than silybin. Biochimica et
Biophysica Acta, 1780, 837–847, 2008.
Jones D, Redefining oxidative stress. Antiox. Redox
Signal 8, 1865–1879, 2006.
Kang JS, Yoon WK, Han M, Lee H, Lee CW, Lee KH,
Han SB, Lee K, Yang KH, Park SK, Kim HM,
Inhibition of atopic dermatitis by topical application
of silymarin in NC/Nga mice. International
Immunopharmacology, 8, 1475-1480, 2008.
Katiyar SK, Korman NJ, Mukhtar H, Agarwal
R, Protective effects of silymarin against
photocarcinogenesis in a mouse skin model. J.Natl.
Cancer Inst, 89, 556-566, 1997.
Katiyar SK, Mantena SK, Meeran SM, Sylimarin protects
epidermal keratinocytes from ultraviolet radiationinduced
apoptosis and DNA damage by nucleotide
excision repair mechanism, Plos One, vol.6, no.6,
11 pages, 2011.
Katiyar SK, Meleth S, Sharma SD, Silymarin, a flavonoid
from milk thistle (Silybum marianum L.), inhibits
UV-induced oxidative stress through targeting
infiltrating CD11b+ cells in mouse skin. Photochem
Photobiol 84, 266–271, 2008.
Katiyar SK, Treatment of sylimarin, a plant flavonoid,
prevents ultraviolet light-induced immune
suppression and oxidative stress in mouse skin. Int.
J. Oncol, 21, 1213-1222, 2010.
Kaur G, Athar M, Alam MS, Dietary supplementation
of silymarin protects against chemically induced
nephorotxicity, inflammation and renal tumor
promotion response. Invest. New Drugs, 28, 703-
713, 2010.
Kim S, Choi MG, Lee H, Lee SK, Kim SH, Kim WW,
Hur SM, Kim JH, Choe JH, Nam SJ, Yang JH, Kim
S, Lee JE, Kim JS, Silibinin suppresses TNF-a
induced MMP-9 expression in gastric cancer
cells through inhibition of the MAPK Pathway.
Molecules, 14, 4301-4310, 2009.
Kravchenko LV, Morozov SV, Tutel’yan VA, Effects of
flavonoids on the resistance of microsomes to lipid
peroxidation in vitro and ex vivo. Bull Exp Biol
Med, 136, 572–575, 2003.
Lahiri-Chatterjee M, Katiyar SK, Mohan RR et al.,
A flavonoid antioxidant, silymarin, affords
exceptionally high protection against tumor
promotion in SENCAR mouse skin tumorigenesis
model. Cancer Res, 59, 622-32, 1999.
Li L, Gao Y, Zhang L, Zeng J, He D, Sun Y, Silibinin
inhibits cell growth and induces apoptosis by
caspase activation, down-regulating surviving
and blocking EGFR_ERK activation in renal cell
carcinoma. Cancer Letters, 272, 61-69, 2008.
Ligeret H, Brault A, Vallerand D, Haddada Y, Haddad PS,
Antioxidant and mitochondrial protective effects
of silibinin in cold preservation–warm reperfusion
liver injury. Journal of Ethnopharmacology, 115,
507–514, 2008.
Lu P, Mamiya T, Lu L, Mouri A, Niwa M, Kim HC, Zou
LB, Nagai T, Yamada K, Ikejima T, Nabeshima T,
Silibinin attenuates cognitive deficits and decreases
of dopamine and serotonin induced by repeated
methamphetamine treatment. Behavioural Brain
Research, 207, 387-393, 2010.
Lu P, Mamiya T, Lu LL, Mouri A, Zou LB, Nagai T,
Hiramatsu M, Ikejima T, Nabeshima T, Silibinin
prevents amyloid b peptide-induced memory
impairment and oxidative stress in mice. British
Journal of Pharmacology, 157, 1270-1277, 2009.
Malekinejad H, Taheri-Broujerdi M, Moradi M, Tabatabaie
SH, Silymarin potentiated the antinociceptive effect
of morphine in mice. Phytotherapy Research, 25,
250-255, 2011.
Mandelker L, Oxidative Stress, Free Radicals, and
Cellular Damage. Studies on Veterinary Medicine,
Oxidative Stress in Applied Basic Research and
Clinical Practice, 5, 2011
Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB,
Silymarin suppresses TNF induced activation of
NF-kappa B, c-Jun N-terminal kinase and apoptosis.
J Immunol, 163, 6800–6809, 1999.
Marrazzo G, Bosco P, Delia FL, Scapagnini G, Giacomo
CD, Malagurnera M, Balvano F, Nicolosi A, Volti
GL, Neuroprotective effect of silibinin in diabetic
mice. Neuroscience Letters, 504, 252-256, 2011.
Murata N, Murakami K, Ozawa Y, Kinoshita N, Irie K,
Shirasawa T, Shimizu T, Silymarin attenuated the
amyloid b plaque burden and improved behavioral
abnormalities in an Alzheimer disease mouse
model. Biosci. Biotechnol. Biochem, 74(11), 2299-
2306, 2010.
Nazemian F, Karimi G, Moatamedi M, Charkazi S,
Shamsara J, Mohammadpor AH, Effect of Sylimarin
administration on TNF-a serum concentration in
peritoneal dialysis. Phytotherapy Research, 24,
1654-1657, 2010.
Nencini C, Giorgi G, Micheli L, Protective effect
of silymarin on oxidative stress in rat brain.
Phytomedicine, 14, 129–135, 2007.
Prabhaba T., Amit K, Manjoor A, Mishara KP,
Radioprotection of plasmid and cellular DNA and
Swiss mice by silibinin, Mutation research, 695, 55-
60, 2010.
Raskovic A, Stilinovic N, Kolarovic J, Vasovic V,
Vukmirovic S, Mikov M, The protective effects
of Silymarin against doxorubicin-induced
cardiotoxicity and hepatotoxicity in rats. Molecules,
16, 8601-8613, 2011.
Rauen U, de Groot H, Cold-induced release of
reactive oxygen species as a decisive mediator of
hypothermia injury to cultured liver cells. Free
Radic Biol Med, 24, 1316–23, 1998.
Raza SS, Khan MM, Ashafaq M, Ahmad A, Khuwaja G,
Khan A, Siddiqui S, Safhi M, Islam F, Silymarin
protects neurons from oxidative stress associated
damages in focal cerebral ischemia: A behavioral,
biochemical and immunohistological study in
Wistar rats. Journal of the Neurological Sciences,
309, 45–54, 2011.
Sangeetha N, Aranganathan S, Nalini N, Silibinin
ameliorates oxidative stress induced aberrant crypt
foci and lipid peroxidation in 1, 2 dimethylhydrazine
induced rat colon cancer. Invest New Drugs, 28,
225–233, 2010.
Sayyah M, Boostani H, Pakseresht S, Malayeri A,
Comparison of Silybum marianum (L) Gertn with fluoxetine in the treatment of obsessive-compulsive
disorder. Progress in Neuro-Psychopharmacology
& Biological Psychiatry, 34, 362-365, 2010.
Shaker E, Mahmoud H, Mnaa S, Silymarin, the
antioxidant component and Silybum marianum
extracts prevent liver damage. Food and Chemical
Toxicology, 48, 803–806, 2010.
Shitany NAE, El-Haggar S, El-Desoky K, Silymarin
prevents Adriamycin-induced cardiotoxicity
and nephrotoxicity in rats. Food and chemical
toxicology, 46, 2422-2428, 2008.
Singh RP, Agarwal R, Flavonoid antioxidant silymarin
and skin cancer. Antioxid Redox Signal, 4, 655-63,
2002.
Singh RP, Agarwal R., Cosmeceuticals and silibinin.
Clinics in Dermatology, 27, 479-484, 2009.
Singhal NK, Srivastava G, Patel DK, Jain SK, Singh
MP. Melatonin or silymarin reduces maneb- and
paraquat-induced Parkinson’s disease phenotype in
the mouse. J Pineal Res, 50, 97–109, 2011.
Soto C, Perez J, Garcia V, Uria E, Vadillo M, Raya L,
Effect of silymarin on kidneys of rats suffering from
alloxan-induced diabetes mellitus. Phytomedicine,
17, 1090-1094, 2010.
Tsai MJ, Liao JF, Lin DY, Huang MC, Liou DY, Yang
HC, Lee HJ, Chen YT, Chi CW, Huang WC, Cheng
H, Silymarin protects spinal cord and cortical cells
against oxidative stress and lipopolysaccharide
stimulation. Neurochemistry International, 57, 867-
875, 2010.
Valenzuela A, Aspillaga M, Vial S, Guerra R, Selectivity
of silymarin on the increase of the glutathione
content in different tissues of the rat. Planta Med,
55, 420–2, 1989.
Valenzuela A, Guerra R, Protective effect of the
flavonoid silybin dihemisuccinate on the toxicity
of phenylhydrazine on rat liver. FEBS Lett., 181,
291–294, 1985.
Wu CH, Huang SM, Yen GC, Silymarin: a novel
antioxidant with antiglycation and anti-inflammatory
properties in vitro and in vivo. Antioxidants&Redox
signaling, vol.14, no.3, 2011
Yin F, Liu J, Ji X, Wang Y, Zidichouski J, Zhang J,
Silibinin: A novel inhibitor of Ab aggregation.
Neurochemistry International, 58, 399-403, 2011.
Yoo HG, Jung SN, Hwang YS, Park JS, Kim MH, Jeong
M, Ahn SJ, Ahn BW, Shin BA, Park RK, Jung
YD, Involvement of NF-kappab and caspases in
silibinin-induced apoptosis of endothelial cells. Int
J Mol Med, 13, 81–86, 2004.
Read_full_article: pdf/vol14/iss2/JMA14-2-2011-Herman.pdf
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 2
Authors: Hildegard Herman1, Luminita Pilat2, Ciprian Mihali1, Cristina Popescu1, Violeta Turcus3, Aurel
Ardelean3, Ardelean Gavril3, Teodora Mariasiu2, Calin Popa2, Anca Hermenean1,2*
Affiliation: 1“Vasile Goldis” Western University of Arad, Institute of Life Sciences, Arad, Romania
2“Vasile Goldis” Western University of Arad, Faculty of Medicine, Pharmacy and Dentistry, Arad, Romania
3“Vasile Goldis” Western University of Arad, Faculty of Natural Sciences, Arad, Romania
Abstract: Silymarin, a flavonolignan from ‘milk thistle’ (Sylibum marianum) plant is used from ancient times as a
hepatoprotective drug. Along the hepatoprotective action silymarin owns also other actions as antioxidant, antilipid
peroxidative, antifibrotic, anti-inflamatory, immunomodulatory, liver regenerating, etc. In Part 1 of this article
we reviewed the milk thistle’s benefic effects in gastrointestinal disorders and its antitumoral activities. Part 2
covers other applications of sylimarin such as antioxidant, antiinflamatory agent, nephroprotector, radiation and
skin protector. It was also studied its neuro-psihiatric and cardiac action.
Keywords: silymarin, oxidative stress, antioxidant, neuroprotection, T cell activation
References: Abbasi BH, Khan MA, Mahmood T, Ahmad M,
Chaudhary MF, Shoot regeneration and free-radical
scavenging activity in Silybum marianum L. Plant
Cell Tiss Organ Cult, 101, 371–376, 2010.
Ahmadi-Ashtiani H, Allameh A, Rastegar H, Soleimani
M, Barkhordari E, Inhibition of cyclooxygenase-2
and inducible nitric oxide synthase by silymarin in
proliferating mesenchymal stem cells: comparison
with glutathione modifiers. J Nat Med, 66, 85–94,
2012.
Altorjay I, Dalmi L, Sári B, Imre S, Balla G, The effect
of silibinin (Legalon) on the free radical scavenger
mechanisms of human erythrocytes in vitro, Acta
Physiol. Hung., 80, 375–380, 1992.
Au AY, Hasenwinkel JM, Frondoza CG, Silybin
inhibits interleukin-1b-induced production of
pro-inflammatory mediators in canine hepatocyte
cultures. J.Vet.Pharmacol.Therap, 34, 120-129,
2010.
Baluchnejadmojarad T, Neuroprotective effect of
silymarin in 6-hydroxydopamine hemi-parkinsonian
rat: Involvement of estrogen receptors and oxidative
stress. Neuroscience Letters, 480, 206-210, 2010.
Becker Schiebe M, Mengs U, Schafer M, Bulitta
M, Hoffman W, Topical use of sylimarin-based
preparation to prevent radiodermatitis. Stahlenther
Onkol., 8, 485-491, 2011.
Bosisio E, Benelli C, Pirola O, Effect of the flavanolignans
of Silybum marianum L. on lipid peroxidation in rat
liver microsomes and freshly isolated hepatocytes.
Pharmacol Res, 25, 147–54, 1992.
Chauhan V, Chauhan A, Oxidative stress in Alzheimer’s
disease. Pathophysiology, 13, 195–208, 2006.
Chtourou Y, Fetoui H, Sefi M, Trabelsi K, Barkallahm
M, Boudawara T, Kallei H, Zeghal N, Silymarin, a
natural antioxidant, protects cerebral cortex against
manganese-induced neurotoxicity in adult rats.
Biometals, 23, 985-996, 2010.
Fu H, Katsumura Y, Lin M, Hata K, Muroya Y, Hatano
Y, Fast Repair Activities Towards dgmp Hydroxyl
Radical Adducts by Silybin and its Analogues, J.
Radiat. Res., 49, 609–614, 2008.
Fu H, Lin M, Katsumura Y, Yokoya A, Hata K, Muroya
Y, Fujii K, Shikazono N, Protective effects of silybin
and analogues against X-ray radiation –induced
damage. Acta Biochim Sin, 42, 489-495, 2010.
Galhardi F, Mesquita K, Monserrat JM, Barros DM,
Effect of silymarin on biochemical parameters of
oxidative stress in aged and young rat brain, Food
and Chemical Toxicology, 47, 2655–2660, 2009.
Garagozloo M, Velardi E, Bruscoli S, Agostini M,
Sante MD, Donato V, Amirghofran Z, Riccardi
C, Silymarin suppress CD+T cell activation and
proliferation: Effects on NF-kB activity and IL-2
production. Pharmacological Research, 61, 405-
409, 2010.
Gažák R, Sedmera P, Vrbacký M, Vostálová J, Drahota
Z, Marhol P, Walterová D, Křen V, Molecular
mechanisms of silybin and 2,3-dehydrosilybin
antiradical activity—role of individual hydroxyl
groups. Free Radical Biology & Medicine 46, 745–
758, 2009.
Gazak R, Svobodova A, Psotova J, Sedmera P, Prikrylova
V, Walterova V, Kren V, Oxidised derivatives of
silybin and their antiradical and antioxidant activity.
Bioorg. Med. Chem. 12, 5677–5687, 2004.
Hou YC, Liou TK, Chern CM, Wang YH, Liao JF, Chang
S, Cho YH, Shen YC, Preventive effect of silymarin
in cerebral ischemia-reperfusion-induced brain
injury in rats possibly through impairing NF-kB and
STAT-1 activation. Phytomedicine, 17, 963-973,
2010.
Huang KX, Gong JX, Xiong W, Yang LX, Wang F,
Tao QF, Wu YH, Li XK, Stöckigt J, Zhao Y, Qu
J, Preparation of silybin 23-esters and evaluation
of their inhibitory ability against LPO and DNA
protective properties. Chinese Chemical Letters, 20,
1030–1033, 2009.
Huber A, Thongphasuk P, Erben G, Lehman WD, Tuma
S, Stremmel W, Chamulitrat W, Significantly
greater antioxidant anticancer activities of
2,3-dehydrosilybin than silybin. Biochimica et
Biophysica Acta, 1780, 837–847, 2008.
Jones D, Redefining oxidative stress. Antiox. Redox
Signal 8, 1865–1879, 2006.
Kang JS, Yoon WK, Han M, Lee H, Lee CW, Lee KH,
Han SB, Lee K, Yang KH, Park SK, Kim HM,
Inhibition of atopic dermatitis by topical application
of silymarin in NC/Nga mice. International
Immunopharmacology, 8, 1475-1480, 2008.
Katiyar SK, Korman NJ, Mukhtar H, Agarwal
R, Protective effects of silymarin against
photocarcinogenesis in a mouse skin model. J.Natl.
Cancer Inst, 89, 556-566, 1997.
Katiyar SK, Mantena SK, Meeran SM, Sylimarin protects
epidermal keratinocytes from ultraviolet radiationinduced
apoptosis and DNA damage by nucleotide
excision repair mechanism, Plos One, vol.6, no.6,
11 pages, 2011.
Katiyar SK, Meleth S, Sharma SD, Silymarin, a flavonoid
from milk thistle (Silybum marianum L.), inhibits
UV-induced oxidative stress through targeting
infiltrating CD11b+ cells in mouse skin. Photochem
Photobiol 84, 266–271, 2008.
Katiyar SK, Treatment of sylimarin, a plant flavonoid,
prevents ultraviolet light-induced immune
suppression and oxidative stress in mouse skin. Int.
J. Oncol, 21, 1213-1222, 2010.
Kaur G, Athar M, Alam MS, Dietary supplementation
of silymarin protects against chemically induced
nephorotxicity, inflammation and renal tumor
promotion response. Invest. New Drugs, 28, 703-
713, 2010.
Kim S, Choi MG, Lee H, Lee SK, Kim SH, Kim WW,
Hur SM, Kim JH, Choe JH, Nam SJ, Yang JH, Kim
S, Lee JE, Kim JS, Silibinin suppresses TNF-a
induced MMP-9 expression in gastric cancer
cells through inhibition of the MAPK Pathway.
Molecules, 14, 4301-4310, 2009.
Kravchenko LV, Morozov SV, Tutel’yan VA, Effects of
flavonoids on the resistance of microsomes to lipid
peroxidation in vitro and ex vivo. Bull Exp Biol
Med, 136, 572–575, 2003.
Lahiri-Chatterjee M, Katiyar SK, Mohan RR et al.,
A flavonoid antioxidant, silymarin, affords
exceptionally high protection against tumor
promotion in SENCAR mouse skin tumorigenesis
model. Cancer Res, 59, 622-32, 1999.
Li L, Gao Y, Zhang L, Zeng J, He D, Sun Y, Silibinin
inhibits cell growth and induces apoptosis by
caspase activation, down-regulating surviving
and blocking EGFR_ERK activation in renal cell
carcinoma. Cancer Letters, 272, 61-69, 2008.
Ligeret H, Brault A, Vallerand D, Haddada Y, Haddad PS,
Antioxidant and mitochondrial protective effects
of silibinin in cold preservation–warm reperfusion
liver injury. Journal of Ethnopharmacology, 115,
507–514, 2008.
Lu P, Mamiya T, Lu L, Mouri A, Niwa M, Kim HC, Zou
LB, Nagai T, Yamada K, Ikejima T, Nabeshima T,
Silibinin attenuates cognitive deficits and decreases
of dopamine and serotonin induced by repeated
methamphetamine treatment. Behavioural Brain
Research, 207, 387-393, 2010.
Lu P, Mamiya T, Lu LL, Mouri A, Zou LB, Nagai T,
Hiramatsu M, Ikejima T, Nabeshima T, Silibinin
prevents amyloid b peptide-induced memory
impairment and oxidative stress in mice. British
Journal of Pharmacology, 157, 1270-1277, 2009.
Malekinejad H, Taheri-Broujerdi M, Moradi M, Tabatabaie
SH, Silymarin potentiated the antinociceptive effect
of morphine in mice. Phytotherapy Research, 25,
250-255, 2011.
Mandelker L, Oxidative Stress, Free Radicals, and
Cellular Damage. Studies on Veterinary Medicine,
Oxidative Stress in Applied Basic Research and
Clinical Practice, 5, 2011
Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB,
Silymarin suppresses TNF induced activation of
NF-kappa B, c-Jun N-terminal kinase and apoptosis.
J Immunol, 163, 6800–6809, 1999.
Marrazzo G, Bosco P, Delia FL, Scapagnini G, Giacomo
CD, Malagurnera M, Balvano F, Nicolosi A, Volti
GL, Neuroprotective effect of silibinin in diabetic
mice. Neuroscience Letters, 504, 252-256, 2011.
Murata N, Murakami K, Ozawa Y, Kinoshita N, Irie K,
Shirasawa T, Shimizu T, Silymarin attenuated the
amyloid b plaque burden and improved behavioral
abnormalities in an Alzheimer disease mouse
model. Biosci. Biotechnol. Biochem, 74(11), 2299-
2306, 2010.
Nazemian F, Karimi G, Moatamedi M, Charkazi S,
Shamsara J, Mohammadpor AH, Effect of Sylimarin
administration on TNF-a serum concentration in
peritoneal dialysis. Phytotherapy Research, 24,
1654-1657, 2010.
Nencini C, Giorgi G, Micheli L, Protective effect
of silymarin on oxidative stress in rat brain.
Phytomedicine, 14, 129–135, 2007.
Prabhaba T., Amit K, Manjoor A, Mishara KP,
Radioprotection of plasmid and cellular DNA and
Swiss mice by silibinin, Mutation research, 695, 55-
60, 2010.
Raskovic A, Stilinovic N, Kolarovic J, Vasovic V,
Vukmirovic S, Mikov M, The protective effects
of Silymarin against doxorubicin-induced
cardiotoxicity and hepatotoxicity in rats. Molecules,
16, 8601-8613, 2011.
Rauen U, de Groot H, Cold-induced release of
reactive oxygen species as a decisive mediator of
hypothermia injury to cultured liver cells. Free
Radic Biol Med, 24, 1316–23, 1998.
Raza SS, Khan MM, Ashafaq M, Ahmad A, Khuwaja G,
Khan A, Siddiqui S, Safhi M, Islam F, Silymarin
protects neurons from oxidative stress associated
damages in focal cerebral ischemia: A behavioral,
biochemical and immunohistological study in
Wistar rats. Journal of the Neurological Sciences,
309, 45–54, 2011.
Sangeetha N, Aranganathan S, Nalini N, Silibinin
ameliorates oxidative stress induced aberrant crypt
foci and lipid peroxidation in 1, 2 dimethylhydrazine
induced rat colon cancer. Invest New Drugs, 28,
225–233, 2010.
Sayyah M, Boostani H, Pakseresht S, Malayeri A,
Comparison of Silybum marianum (L) Gertn with fluoxetine in the treatment of obsessive-compulsive
disorder. Progress in Neuro-Psychopharmacology
& Biological Psychiatry, 34, 362-365, 2010.
Shaker E, Mahmoud H, Mnaa S, Silymarin, the
antioxidant component and Silybum marianum
extracts prevent liver damage. Food and Chemical
Toxicology, 48, 803–806, 2010.
Shitany NAE, El-Haggar S, El-Desoky K, Silymarin
prevents Adriamycin-induced cardiotoxicity
and nephrotoxicity in rats. Food and chemical
toxicology, 46, 2422-2428, 2008.
Singh RP, Agarwal R, Flavonoid antioxidant silymarin
and skin cancer. Antioxid Redox Signal, 4, 655-63,
2002.
Singh RP, Agarwal R., Cosmeceuticals and silibinin.
Clinics in Dermatology, 27, 479-484, 2009.
Singhal NK, Srivastava G, Patel DK, Jain SK, Singh
MP. Melatonin or silymarin reduces maneb- and
paraquat-induced Parkinson’s disease phenotype in
the mouse. J Pineal Res, 50, 97–109, 2011.
Soto C, Perez J, Garcia V, Uria E, Vadillo M, Raya L,
Effect of silymarin on kidneys of rats suffering from
alloxan-induced diabetes mellitus. Phytomedicine,
17, 1090-1094, 2010.
Tsai MJ, Liao JF, Lin DY, Huang MC, Liou DY, Yang
HC, Lee HJ, Chen YT, Chi CW, Huang WC, Cheng
H, Silymarin protects spinal cord and cortical cells
against oxidative stress and lipopolysaccharide
stimulation. Neurochemistry International, 57, 867-
875, 2010.
Valenzuela A, Aspillaga M, Vial S, Guerra R, Selectivity
of silymarin on the increase of the glutathione
content in different tissues of the rat. Planta Med,
55, 420–2, 1989.
Valenzuela A, Guerra R, Protective effect of the
flavonoid silybin dihemisuccinate on the toxicity
of phenylhydrazine on rat liver. FEBS Lett., 181,
291–294, 1985.
Wu CH, Huang SM, Yen GC, Silymarin: a novel
antioxidant with antiglycation and anti-inflammatory
properties in vitro and in vivo. Antioxidants&Redox
signaling, vol.14, no.3, 2011
Yin F, Liu J, Ji X, Wang Y, Zidichouski J, Zhang J,
Silibinin: A novel inhibitor of Ab aggregation.
Neurochemistry International, 58, 399-403, 2011.
Yoo HG, Jung SN, Hwang YS, Park JS, Kim MH, Jeong
M, Ahn SJ, Ahn BW, Shin BA, Park RK, Jung
YD, Involvement of NF-kappab and caspases in
silibinin-induced apoptosis of endothelial cells. Int
J Mol Med, 13, 81–86, 2004.
*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