Silymarin is a bioflavonoid complex extract derived from dry seeds of Milk thistle [(Silybum marianum(L.) Gaernt. (Fam. Asteraceae/Compositaceae)] whose hepatoprotective effect has clinically been proved. Low toxicity, favorable pharmacokinetics, powerful antioxidant, detoxifying, preventive, protective and regenerative effects and side effects similar to placebo make silymarin extremely attractive and safe for therapeutic use. The medicinal properties of silymarin and its main component silibinin have been studied in the treatment of Alzheimer's disease, Parkinson's disease, sepsis, burns, osteoporosis, diabetes, cholestasis and hypercholesterolemia. Owing to its apoptotic effect, without cytotoxic effects, silymarin possesses potential applications in the treatment of various cancers. Silymarin is being examined as a neuro-, nephro- and cardio-protective in the damage of different etiologies due to its strong antioxidant potentials. Furthermore, it has fetoprotective (against the influence of alcohol) and prolactin effects and is safe to be used during pregnancy and lactation. Finally, the cosmetics industry is examining the antioxidant and UV-protective effects of silymarin. Further clinical studies and scientific evidence that silymarin and silibinin are effective in the therapy of various pathologies are indispensable in order to confirm their different flavonolignan pharmacological effects.
KrenV., WalterováD. (2005) Silybin and silymarin-new effects and applications. Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia, 149, 29–41.
2.
KrollD.J., ShawH.S., OberliesN.H. (2007) Milk thistle nomenclature: Why it matters in cancer research and pharmacokinetic studies. Integrative Cancer Therapies, 6, 110–119.
3.
AbenavoliL., CapassoR., MilicN., CapassoF. (2010) Milk thistle in liver diseases: past, present and future. Phytotherapy Research, 24, 1423–1432.
4.
AbenavoliL., AvielloG., CapassoR., MilicN., CapassoF. (2011) Milk thistle for treatment of nonalcoholic fatty liver disease. Hepatitis Monthly, 11, 173–177.
5.
TzengJ.I., ChenM.F., ChungH.H., ChengJ.T. (2013) Silymarin decreases connective tissue growth factor to improve liver fibrosis in rats treated with carbon tetrachloride. Phytotherapy Research, 27, 1023–1028.
6.
Kwon doY., JungY.S., KimS.J., KimY.S., ChoiD.W., KimY.C. (2013) Alterations in sulfur amino acid metabolism in mice treated with silymarin: a novel mechanism of its action involved in enhancement of the antioxidant defense in liver. Planta Medica, 79, 997–1002.
7.
PradhanS.C., GirishC. (2006) Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. The Indian Journal of Medical Research, 124, 491–504.
8.
ColturatoC.P., ConstantinR.P., MaedaA.S.Jr., ConstantinR.P., YamamotoN.S., BrachtA., Ishii-IwamotoE.L., ConstantinJ. (2012) Metabolic effects of silibinin in the rat liver. Chemico-biological Interactions, 195, 119–132.
9.
ShakerE., MahmoudH., MnaaS. (2010) Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association, 48, 803–806.
10.
ParésA., PlanasR., TorresM., CaballeríaJ., ViverJ.M., AceroD., PanésJ., RigauJ., SantosJ., RodésJ. (1998) Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. Journal of Hepatology, 28, 615–621.
11.
MayerK.E., MyersR.P., LeeS.S. (2005) Silymarin treatment of viral hepatitis: a systematic review. Journal of Viral Hepatitis, 12, 559–567.
12.
KimY.C., KimE.J., LeeE.D., KimJ.H., JangS.W., KimY.G., KwonJ.W., KimW.B., LeeM.G. (2003) Comparative bioavailability of silibinin in healthy male volunteers. International Journal of Clinical Pharmacology and Therapeutics, 41, 593–596.
13.
WuJ.W., LinL.C., TsaiT.H. (2009) Drug–drug interactions of silymarin on the perspective of pharmacokinetics. Journal of Ethnopharmacology, 121, 185–193.
14.
GhoshA., GhoshT., JainS. (2010) Silymarin- a review on the pharmacodynamics and bioavailability enhancement approaches. Journal of Pharmaceutical Science and Technology, 2, 348–355, [15] Wen Z, Dumas TE, Schrieber SJ, Hawke RL, Fried MW, Smith PC. (2008) Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 36, 65–72.
15.
CalaniL., BrighentiF., BruniR., Del RioD. (2012) Absorption and metabolism of milk thistle flavanolignans in humans. Phytomedicine, 20, 40–46.
16.
Post-WhiteJ., LadasE.J., KellyK.M. (2007) Advances in the Use of Milk Thistle (Silybum marianum). Integrative Cancer Therapies, 6, 104–109.
17.
BrantleyS.J., OberliesN.H., KrollD.J., PaineM.F. (2010) Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations. The Journal of Pharmacology and Experimental Therapeutics, 332, 1081–1087.
18.
YinF., LiuJ., JiX., WangY., ZidichouskiJ., ZhangJ. (2011) Silibinin: a novel inhibitor of Aβ aggregation. Neurochemistry International, 58, 399–403.
19.
TotaS., KamatP.K., ShuklaR., NathC. (2011) Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment. Behavioural Brain Research, 221, 207–215.
20.
MarrazzoG., BoscoP., La DeliaF., ScapagniniG., Di GiacomoC., MalaguarneraM., GalvanoF., NicolosiA., Li VoltiG. (2011) Neuroprotective effect of silibinin in diabetic mice. Neuroscience Letters, 504, 252–256.
21.
LuP., MamiyaT., LuL., MouriA., NiwaM., KimH.C., ZouL.B., NagaiT., YamadaK., IkejimaT., NabeshimaT. (2010) Silibinin attenuates cognitive deficits and decreases of dopamine and serotonin induced by repeated methamphetamine treatment. Behavioural Brain Research, 207, 387–393.
22.
BaluchnejadmojaradT., RoghaniM., MafakheriM. (2010) Neuroprotective effect of silymarin in 6-hydroxydopamine hemi-Parkinsonian rat: Involvement of estrogen receptors and oxidative stress. Neuroscience Letters, 480, 206–210.
23.
KaurM., AgarwalR. (2007) Silymarin and epithelial cancer chemoprevention: how close we are to bedside?Toxicology and Applied Pharmacology, 224, 350–359.
24.
BhatiaN., ZhaoJ., WolfD.M., AgarwalR. (1999) Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin. Cancer Letters, 147, 77–84.
25.
ZhoJ., SharmaY., AgarwalR. (1999) Significant inhibition by the flavonoid antioxidant silymarin against 12-0-tetradecanoylphorbol 13-acetate caused modulation of antioxidant and inflammatory enzymes, and cyclooxygenase 2 and interleukin-1 alpha expression in SENCAR mouse epidermis: Implications in the prevention of stage I tumor promotion. Molecular Carcinogenesis, 26, 321–333.
26.
ZiX., AgarwalR. (1999) Modulation of mitogen-activated protein kinase activation and cell cycle regulators by the potent skin cancer preventive agent silymarin. Biochemical and Biophysical Research Communications, 263, 528–536.
27.
SinghR.P., TyagiA.K., ZhaoJ., AgarwalR. (2002) Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis. Carcinogenesis, 23, 499–510.
28.
KatiyarS.K., KormanN.J., MukhtarH., AgarwalR. (1997) Protective effects of silymarin against photocarcinogenesis in a mouse skin model. Journal of the National Cancer Institute, 89, 556–566.
29.
Katiyar-SantoshK. (2002) Treatment of silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin. International Journal of Oncology, 21, 1213–1222.
30.
PinnellS.R. (2003) Cutaneous photodamage, oxidate stress, and topical antioxidant protection. Journal of the American Academy of Dermatology, 48, 1–19.
31.
LiuW., OtkurW., LiL., WangQ., HeH., ZangL., HayashiT., TashiroS., OnoderaS., XiaM., IkejimaT. (2013) Interference of silibinin with IGF-1R signalling pathways protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis. Biochemical and Biophysical Research Communications, 432, 314–319.
32.
LiuW., OtkurW., LiL., WangQ., HeH., YeY., ZhangY., HayashiT., TashiroS., OnoderaS., IkejimaT. (2013) Autophagy induced by silibinin protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis. Journal of Photochemistry and Photobiology. B: Biology, 123, 23–31.
33.
SinghR.P., AgarwalR. (2005) Mechanisms and preclinical efficacy of silibinin in preventing skin cancer. European Journal of Cancer, 41, 1969–1979.
34.
RamakrishnanG., AugustineT.A., JaganS., VinodhkumarR., DevakiT. (2007) Effect of silymarin on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Experimental Oncology, 29, 39–44.
35.
Brandon-WarnerE., SuggJ.A., SchrumL.W., McKillopI.H. (2010) Silibinin inhibits ethanol metabolism and ethanol-dependent cell proliferation in an in vitro model of hepatocellular carcinoma. Cancer Letters, 291, 120–129.
36.
MomenyM., KhorramizadehM.R., GhaffariS.H., YousefiM., YekaninejadM.S., EsmaeiliR., JahanshiriZ., NooridaloiiM.R. (2008) Effects of silibinin on cell growth and invasive properties of a human hepatocellular carcinoma cell line, HepG-2, through inhibition of extracellular signal-regulated kinase 1/2 phosphorylation. European Journal of Pharmacology, 591, 13–20.
37.
ZiX., FeyesD.K., AgarwalR. (1998) Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast cancer cells MDA-MB 468: induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins. Clinical Cancer Research: an official journal of the American Association for Cancer Research, 4, 1055–1064.
38.
LinZ.Y., ChuangW.L. (2011) Influence of silibinin on differential expressions of total cytokine genes in human hepatocellular carcinoma cell lines. Biomedicine and Preventive Nutrition, 1, 91–94.
39.
LeeS.O., JeongY.J., ImH.G., KimC.H., ChangY.C., LeeI.S. (2007) Silibinin suppresses PMA-induced MMP-9 expression by blocking the AP-1 activation via MAPK signaling pathways in MCF-7 human breast carcinoma cells. Biochemical and Biophysical Research Communications, 354, 165–171.
40.
KimS., ChoiJ.H., LimH.I., LeeS.K., KimW.W., KimJ.S., KimJ.H., ChoeJ.H., YangJ.H., NamS.J., LeeJ.E. (2009) Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells. Phytomedicine, 16, 573–580.
41.
XuP., YinQ., ShenJ., ChenL., YuH., ZhangZ., LiY. (2013) Synergistic inhibition of breast cancer metastasis by silibinin-loaded lipid nanoparticles containing TPGS. International Journal of Pharmaceutics, 454, 21–30.
42.
LuW., LinC., KingT.D., ChenH., ReynoldsR.C., LiY. (2012) Silibinin inhibits Wnt/β-catenin signaling by suppressing Wnt co-receptor LRP6 expression in human prostate and breast cancer cells. Cellular Signalling, 24, 2291–2296.
43.
GalloD., GiacomelliS., FerliniC., RaspaglioG., ApollonioP., PrisleiS., RivaA., MorazzoniP., BombardelliE., ScambiaG. (2003) Antitumour activity of the silybin-phosphatidylcholine complex, IdB 1016, against human ovarian cancer. European Journal of Cancer, 39, 2403–2410.
HuangQ., WuL.J., TashiroS., OnoderaS., LiL.H., IkejimaT. (2005) Silymarin augments human cervical cancer HeLa cell apoptosis via P38/JNK-MAPK pathways in serum-free medium. Journal of Asian Natural Products Research, 7, 701–709.
46.
García-MaceiraP., MateoJ. (2009) Silibinin inhibits hypoxia-inducible factor-1α and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy. Oncogene, 28, 313–324.
47.
TyagiA., AgarwalC., HarrisonG., GlodeL.M., AgarwalR. (2004) Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-CDK-cyclin cascade, and caspase 3 and PARP cleavages. Carcinogenesis, 25, 1711–1720.
48.
VinhP.Q., SugieS., TanakaT., HaraA., YamadaY., KatayamaM., DeguchiT., MoriH. (2002) Chemopreventive effects of a flavonoid antioxidant silymarin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice. Japanese Journal of Cancer Research: Gann, 93, 42–49.
49.
SinghR.P., TyagiA., SharmaG., MohanS., AgarwalR. (2008) Oral silibinin inhibits in vivo human bladder tumor xenograft growth involving down-regulation of survivin. Clinical Cancer Research: an official journal of the American Association for Cancer Research, 14, 300–308.
50.
SinghR.P., MallikarjunaG.U., SharmaG., DhanalakshmiS., TyagiA.K., ChanD.C., AgarwalC., AgarwalR. (2004) Oral silibinin inhibits lung tumor growth in athymic nude mice and forms a novel chemocombination with doxorubicin targeting NF-kB-mediated inducible chemoresistance. Clinical Cancer Research: an official journal of the American Association for Cancer Research, 10, 8641–8647.
51.
SadavaD., KaneS.E. (2013) Silibinin reverses drug resistance in human small-cell lung carcinoma cells. Cancer Letters, 339, 102–106.
52.
SinghR.P., DeepG., ChittezhathM., KaurM., Dwyer-NieldL.D., MalkinsonA.M., AgarwalR. (2006) Effect of silibinin on the growth and progression of primary lung tumors in mice. Journal of the National Cancer Institute, 98, 846–855.
53.
ChittezhathM., DeepG., SinghR.P., AgarwalC., AgarwalR. (2008) Silibinin inhibits cytokine-induced signaling cascades and down-regulates inducible NO synthase in human lung carcinoma A549 cells. Molecular Cancer Therapeutics, 7, 1817–1826.
54.
CufíS., BonaviaR., Vazquez-MartinA., Corominas-FajaB., Oliveras-FerrarosC., CuyàsE., Martin-CastilloB., Barrajón-CatalánE., VisaJ., Segura-CarreteroA., Bosch-BarreraJ., JovenJ., MicolV., MenendezJ.A. (2013) Silibinin meglumine, a water-soluble form of milk thistle silymarin, is an orally active anti-cancer agent that impedes the epithelial-to-mesenchymal transition (EMT) in EGFR-mutant non-small-cell lung carcinoma cells. Food and Chemical Toxicology: an international journal published for the British Industrial Biological Research Association, 60, 360–368.
55.
Davis-SearlesP.R., NakanishiY., KimN.C., GrafT.N., OberliesN.H., WaniM.C., WallM.E., AgarwalR., KrollD.J. (2005) Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. Cancer Research, 65, 4448–4457.
56.
SinghR.P., AgarwalR. (2004) A cancer chemopreventive agent silibinin, targets mitogenic and survival signaling in prostate cancer. Mutation Research, 555, 21–32.
57.
VerschoyleR.D., GreavesP., PatelK., MarsdenD.A., BrownK., StewardW.P., GescherA.J. (2008) 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.
58.
RainaK., BlouinM.J., SinghR.P., MajeedN., DeepG., VargheseL., GlodéL.M., GreenbergN.M., HwangD., CohenP., PollakM.N., AgarwalR. (2007) Dietary feeding of silibinin inhibits prostate tumor growth and progression in transgenic adenocarcinoma of the mouse prostate model. Cancer Research, 67, 11083–11091.
59.
SuC.H., ChenL.J., LiaoJ.F., ChengJ.T. (2013) Increase of phosphatase and tensin homolog by silymarin to inhibit human pharynx squamous cancer. Journal of Medicinal Food, 16, 778–784.
HoganF.S., KrishnegowdaN.K., MikhailovaM., KahlenbergM.S. (2007) Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer. The Journal of Surgical Reasearch, 143, 58–65.
62.
KohnoH., TanakaT., KawabataK., HiroseY., SugieS., TsudaH., MoriH. (2002) Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. International Journal of Cancer, 101, 461–468.
63.
SangeethaN., ViswanathanP., BalasubramanianT., NaliniN. (2012) Colon cancer chemopreventive efficacy of silibinin through perturbation of xenobiotic metabolizing enzymes in experimental rats. European Journal of Pharmacology, 674, 430–438.
64.
SinghR.P., GuM., AgarwalR. (2008) Silibinin inhibits colorectal cancer growth by inhibiting tumor cell proliferation and angiogenesis. Cancer Research, 68, 2043–2050.
65.
NambiarD., PrajapatiV., AgarwalR., SinghR.P. (2012) In vitro and in vivo anticancer efficacy of silibinin against human pancreatic cancer BxPC-3 and PANC-1 cells. Cancer Letters, pii: S0304–3835(12)00539–3. doi: 10.1016/j.canlet.2012.09.004.
66.
KangS.N., LeeM.H., KimK.M., ChoD., KimT.S. (2001) Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by silibinin: involvement of protein kinase C. Biochemical Pharmacology, 61, 1487–1495.
67.
ZhongX., ZhuY., LuQ., ZhangJ., GeZ., ZhengS. (2006) Silymarin causes caspases activation and apoptosis in K562 leukemia cells through inactivation of Akt pathway. Toxicology, 227, 211–216.
68.
ZhangJ., LuanQ., LiuY., LeeD.Y., WangZ. (2011) A comparison of the diastereoisomers, silybin A and silybin B, on the induction of apoptosis in K562 cells. Natural Product Communications, 6, 1653–1656.
69.
SonnenbichlerJ., ScaleraF., SonnenbichlerI., WeyhenmeyerR. (1999) Stimulatory effects of silibinin and silicristin from the milk thistle Silybum marianum on kidney cells. The Journal of Pharmacology and Experimental Therapeutics, 290, 1375–1383.
70.
DietzmannJ., ThielU., AnsorgeS., NeumannK.H., TagerM. (2002) Thiol-inducing and immunoregulatory effects of flavonoids in peripheral blood mononuclear cells from patients with end-stage diabetic nephropathy. Free Radical Biology and Medicine, 33, 1347–1354.
71.
Dashti-KhavidakiS., ShahbaziF., KhaliliH., Lessan-PezeshkiM. (2012) Potential renoprotective effects of silymarin against nephrotoxic drugs: a review of literature. Journal of Pharmaceutical Sciences, 15, 112–123.
72.
NenciniC., GiorgiG., MicheliL. (2007) Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine, 14, 129–135.
NabaviS.M., SuredaA., NabaviS.F., LatifiA.M., MoghaddamA.H., HellioC. (2012) Neuroprotective effects of silymarin on sodium fluoride-induced oxidative stress. Journal of Fluorine Chemistry, 142, 79–82.
75.
SalamoneF., GalvanoF., MarinoA., PaternostroC., TibulloD., BucchieriF., MangiameliA., ParolaM., BugianesiE., Li VoltiG. (2012) Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis. Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 44, 334–342.
76.
AnestopoulosI., KavoA., TentesI., KortsarisA., PanayiotidisM., LazouA., PappaA. (2013) Silibinin protects H9c2 cardiac cells from oxidative stress and inhibits phenylephrine-induced hypertrophy: potential mechanisms. The Journal of Nutritional Biochemistry, 24, 586–594.
77.
KrecmanV., SkottováN., WalterováD., UlrichováJ., SimánekV. (1998) Silymarin inhibits the development of diet-induced hypercholesterolemia in rats. Planta Medica, 64, 138–142.
78.
RadjabianT., HuseiniH.F. (2010) Anti-hyperlipidemic and anti-atherosclerotic activities of silymarins from cultivated and wild plants of Silybum marianum L. with different contents of flavonolignans. Iranian Journal of Pharmacology and Therapeutics, 9, 63–67.
79.
HuseiniH.F., LarijaniB., HeshmatR., FakhrzadehH., RadjabipourB., ToliatT., RazaM. (2006) The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytotherapy Research, 20, 1036–1039.
80.
LirussiF., BeccarelloA., ZanetteG., De MonteA., DonadonV., VelussiM., CrepaldiG. (2002) Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent. Diabetes, Nutrition and Metabolism, 15, 222–231.
81.
MesheimishB.A.R., HussainS.A.R., IsmailS.H., HusseinK.I., SulaimanA.A. (2007) Hypolipidemic effect of silymarin in dyslipidaemia of different etiologies. Journal of the Faculty of Medicine, Baghdad, 49, 449–456.
82.
VelussiM., CernigoiA.M., De MonteA., DapasF., CaffauC., ZilliM. (1997) Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. Journal of Hepatology, 26, 871–879.
83.
AbenavoliL., MilicN., CapassoF. (2012) Anti-oxidant therapy in non-alcoholic fatty liver disease: the role of silymarin. Endocrine, 42, 754–755.
84.
TokluH.Z., Tunali AkbayT., Velioglu-OguncA., ErcanF., GedikN., Keyer-UysalM., SenerG. (2008) Silymarin, the antioxidant component of Silybum marianum, prevents sepsis-induced acute lung and brain injury. The Journal of Surgical Research, 145, 214–222.
85.
Seidlová-WuttkeT., BeckerV., ChristoffelH., JarryW., WuttkeD. (2003) Silymarin is a selective estrogen receptor β (ERβ) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx) rats. Journal of Steroid Biochemistry & Molecular Biology, 86, 179–188.
86.
El-ShitanyN.A., HegazyS., El-DesokyK. (2010) Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats. Phytomedicine, 17, 116–125.
87.
AshkavandZ., MalekinejadH., AmniattalabA., Rezaei-GolmishehA., VishwanathB.S. (2012) Silymarin potentiates the anti-inflammatory effects of Celecoxib on chemically induced osteoarthritis in rats. Phytomedicine, 19, 1200–1205.
88.
MorelandN., La GrangeL., MontoyaR. (2002) Impact of in utero exposure to EtOH on corpus callosum development and paw preference in rats: protective effects of silymarin. BMC Complementary and Alternative Medicine, 2, 10.
89.
NeeseS., La GrangeL., TrujilloE., RomeroD. (2004) The effects of ethanol and silymarin treatment during gestation on spatial working memory. BMC Complementary and Alternative Medicine, 4, 4.
90.
CapassoR., AvielloG., CapassoF., SavinoF., IzzoA.A., LemboF., BorrelliF. (2004) Silymarin BIO-C®, an extract from Silybum marianum fruits, induces hyperprolactinemia in intact female rats. Phytomedicine, 16, 839–844.
91.
GharagozlooM., VelardiE., BruscoliS., AgostiniM., Di SanteM., DonatoV., AmirghofranZ., RiccardiC. (2010) Silymarin suppress CD4+ T cell activation and proliferation: Effects on NF-kB activity and IL-2 production. Pharmacological Research: the Official Journal of the Italian Pharmacological Society, 61, 405–409.
92.
BannwartC.F., Nakaira-TakahagiE., GolimM.A., MedeirosL.T.L., RomãoM., WeelI.C., PeraçoliM.T. (2010) Downregulation of nuclear factor kappa B (NF-kB) pathway by silibinin inhuman monocytes challenged with Paracoccidioides brasiliensis. Life Sciences, 86, 880–886.
93.
ChoiY.H., JinG.Y., GuoH.S., PiaoH.M., LiLc, LiG.Z., LinZ.H., YanG.H. (2012) Silibinin attenuates allergic airway inflammation in mice. Biochemical and Biophysical Research Communications, 427, 450–455.
94.
DehmlowC., ErhardJ., De GrootH. (1996) Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silybinin. Hepatology, 23, 749–754.
95.
DehmlowC., MurawskiN., de GrootH. (1996) Scavenging of reactive oxygen species and inhibition of arachidonic acid metabolism by silibinin in human cells. Life Sciences, 58, 1591–1600.
96.
KangJ.S., JeonY.J., ParkS.K., YangK.H., KimH.M. (2004) Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1β and prostaglandin E2 synthesis by silymarin. Biochemical Pharmacology, 67, 175–181.
97.
TokluH.Z., Tunali-AkbayT., ErkanliG., YükselM., ErcanF., SenerG. (2007) Silymarin, the antioxidant component of Silybum marianum, protects against burn-induced oxidative skin injury. Burns, 33, 908–916.
98.
CrocenziF.A., BasiglioC.L., PérezL.M., PortesioM.S., PozziE.J., RomaM.G. (2005) Silibinin prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: Possible involvement of cAMP. Biochemical Pharmacology, 69, 1113–1120.
99.
SinghR.P., AgarwalR. (2009) Cosmeceuticals and silibinin. Clinics in Dermatology, 27, 479–484.
