The Chemical Constituents and Pharmacological Actions of Silybum Marianum

Author(s): Fangxue Xu, Chunchao Han*, Yujuan Li, Mengmeng Zheng, Xiaozhi Xi, Chaoqun Hu, Xiaowei Cui, Hui Cao

Journal Name: Current Nutrition & Food Science

Volume 15 , Issue 5 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


This review presents the chemical constituents and pharmacological actions of Silybum marianum. These chemical constituents include flavonolignans, fatty acids, phenolics and other chemical constituents. Furthermore, flavonolignans constituents include silymarin isosilychristin, silychristin, silydianin, silybin A, silybin B, isosilybin A, isosilybin B, etc. Pharmacological actions include a well curative effect on non-alcoholic steatohepatitis, UV damage, varieties of cancers, diabetes. In addition, its pharmacological actions include anti-inflammatory, anti-depression and more pharmacological actions. This paper will enable Silybum marianum lay the foundation for producing high and sustainable productions in the future.

Keywords: Chemical constituents, fatty acids, flavonolignans, pharmacological actions, phenolics, Silybum marianum.

Kubatka P, Kapinová A, Kello M, et al. Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer. Eur J Nutr 2016; 55(3): 955-65.
Wang CY, Bai XY, Wang CH. Traditional Chinese medicine: a treasured natural resource of anticancer drug research and development. Am J Chin Med 2014; 42(3): 543-59.
Wallace SN, Carrier DJ, Clausen EC. Batch solvent extraction of flavanolignans from milk thistle (Silybum marianum L. Gaertner). Phytochem Anal 2005; 16(1): 7-16.
Qin NB, Li SG, Yang XY, et al. Bioactive terpenoids from Silybum marianum and their suppression on NO release in LPS-induced BV-2 cells and interaction with iNOS. Bioorg Med Chem Lett 2017; 27(10): 2161-5.
Hackett ES, Twedt DC, Gustafson DL. Milk thistle and its derivative compounds: a review of opportunities for treatment of liver disease. J Vet Intern Med 2013; 27(1): 10-6.
Polyak SJ, Morishima C, Lohmann V, et al. Identification of hepatoprotective flavonolignans from silymarin. Proc Natl Acad Sci 2010; 107(13): 5995-9.
Karakuş A, Değer Y. Protective effect of Silybum marianum and Taraxacum officinale extracts against oxidative kidney injuries induced by carbon tetrachloride in rats. Ren Fail 2017; 39(1): 1-6.
Palomino OM, Gouveia NM, Ramos S, et al. Protective effect of Silybum marianum and silibinin on endothelial cells submitted to high glucose concentration. Planta Med 2017; 83(1-02): 97-103.
Serçe A, Toptancı BÇ, Tanrıkut SE, et al. Assessment of the antioxidant activity of Silybum marianum seed extract and its protective effect against DNA oxidation, protein damage and lipid peroxidation. Food Technol Biotechnol 2016; 54(4): 455-61.
El-Garhy HA, Khattab S, Moustafa MM, et al. Silybin content and overexpression of chalcone synthase genes in Silybum marianum L. plants under abiotic elicitation. Plant Physiol Biochem 2016; 108: 191-202.
Dietz BM, Hajirahimkhan A, Dunlap TL, et al. Botanicals and their bioactive phytochemicals for women’s health. Pharmacol Rev 2016; 68(4): 1026-73.
Sajadi SM, Nasrollahzadeh M. Aqueous extract from seeds of Silybum marianum L. as a green material for preparation of the Cu/Fe3O4 nanoparticles: A magnetically recoverable and reusable catalyst for the reduction of nitroarenes. J Colloid Interface Sci 2016; 469: 93-8.
Flora K, Hahn M, Rosen H, et al. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998; 93(2): 139-43.
Smith WA, Lauren DR, Burgess EJ, et al. A silychristin isomer and variation of flavonolignan levels in milk thistle (Silybum marianum) fruits. Planta Med 2005; 71(9): 877-80.
Graf TN, Cech NB, Polyak SJ, et al. A validated UHPLC-tandem mass spectrometry method for quantitative analysis of flavonolignans in milk thistle (Silybum marianum) extracts. J Pharm Biomed Anal 2016; 126: 26-33.
Zhao Y, Chen B. Simultaneous determination of abietane-type diterpenes, flavonolignans and phenolic compounds in compound preparations of Silybum marianum and Salvia miltiorrhiza by HPLC-DAD-ESI MS. J Pharm Biomed Anal 2005; 38(3): 564-70.
Tůmová L, Gallová K. Silybum marianum in vitro. Ceska a Slovenska Farmacie 2004; 53(3): 135-40.
Fibigr J, Šatínský D, Solich P. A new approach to the rapid separation of isomeric compounds in a Silybum marianum extract using UHPLC core-shell column with F5 stationary phase. J Pharm Biomed Anal 2017; 134: 203-13.
Hadad GM, Emara S, Abdel-Salam RA. Validated optimized method for simultaneous analysis of active silymarin components and dimethyl-4,4-dimethoxy-5,6,5,6-dimethylene dioxybiphenyl-2,2-dicarboxylate in a pharmaceutical preparation by use of a monolithic silica C-18 column. Chromatographia 2009; 70(1-2): 217-21.
Li W, Han J, Li Z, et al. Preparative chromatographic purification of diastereomers of silybin and their quantification in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2008; 862(1-2): 51-7.
Wang K, Zhang H, Shen L, et al. Rapid separation and characterization of active flavonolignans of Silybum marianum by ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry. J Pharm Biomed Anal 2010; 53(4): 1053-7.
Cheilari A, Sturm S, Intelmann D, et al. Head-to-head comparison of ultra-high-performance liquid chromatography with diode array detection versus quantitative nuclear magnetic resonance for the quantitative analysis of the silymarin complex in Silybum marianum fruit extracts. J Agric Food Chem 2016; 64(7): 1618-26.
Kvasnicka F, Bíba B, Sevcik R, et al. Analysis of the active components of silymarin. J Chromatogr A 2003; 990(1-2): 239-45.
Hassan EM, Khamis EF, El-Kimary EI. Development of a differential pulse voltammetric method for the determination of Silymarin/Vitamin E acetate mixture in pharmaceuticals. Talanta 2008; 74(4): 773-8.
Chan WK, Nik Mustapha NR, Mahadeva S. A randomized trial of silymarin for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2017; 15(12): 1940-9.e8.
Ni X. Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD). Am J Transl Res 2016; 8(2): 1073-81.
Aller R, Izaola O, Gomez S, et al. Effect of silymarin plus vitamin E in patients with non-alcoholic fatty liver disease. A randomized clinical pilot study. Eur Rev Med Pharmacol Sci 2015; 19(16): 3118-24.
Fehér P, Ujhelyi Z, Varadi J, et al. Efficacy of pre- and post-treatment by topical formulations containing dissolved and suspended Silybum marianum against UVB-induced oxidative stress in guinea pig and on HaCaT keratinocytes. Molecules 2016; 21(10): E1269.
Katiyar SK, Meleth S. Silymarin, a flavonoid from milk thistle (Silybum marianum L.), inhibits UV-induced oxidative stress through targeting infiltrating CD11b+ cells in mouse skin. Photochem Photobiol 2008; 84(2): 266-71.
Zi X, Feyes D, Agarwal R. Anti-carcinogenic 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 cyclin. Clin Cancer Res 1998; 4(4): 1055-64.
Eo HJ, Park GH. Inhibition of Wnt signaling by silymarin in human colorectal cancer cells. Biomol Ther (Seoul) 2016; 24(4): 380-6.
Montgomery A, Adeyeni T, San K, et al. Curcumin sensitizes silymarin to exert synergistic anticancer activity in colon cancer cells. J Cancer 2016; 7(10): 1250-7.
Su CH, Chen LJ, Liao JF. Increase of phosphatase and tensin homolog by silymarin to inhibit human pharynx squamous cancer. J Med Food 2013; 16(9): 778-84.
Snima KS, Arunkumar P, Jayakumar R, et al. Silymarin encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles: a prospective candidate for prostate cancer therapy. J Biomed Nanotechnol 2014; 10(4): 559-70.
Youn CK, Cho SI, Lee MY, et al. Inhibition of ERK1/2 by silymarin in mouse mesangial cells. Korean J Physiol Pharmacol 2017; 21(1): 117-24.
Elyasi S, Hosseini S, Niazi Moghadam MR, et al. Effect of oral silymarin administration on prevention of radiotherapy induced mucositis: a randomized, double-blinded, placebo-controlled clinical trial. Phytother Res 2016; 30(11): 1879-85.
Meng R, Mahadevan J, Oseid E, et al. Silymarin activates c-AMP phosphodiesterase and stimulates insulin secretion in a glucose-dependent manner in HIT-T15 cells. Antioxidants (Basel) 2016; 5(4): 47.
Voroneanu L, Nistor I, Dumea R, et al. Silymarin in type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. J Diabetes Res 2016; 5147468.
Ebrahimpour Koujan S, Gargari BP, Mobasseri M, et al. Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial. Phytomedicine 2015; 22(2): 290-6.
Thakare VN, Dhakane VD, Patel BM. Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus. Pharmacol Rep 2016; 68(5): 1020-7.
Khoshnoodi M, Fakhraei N, Dehpour AR. Possible involvement of nitric oxide in antidepressant-like effect of silymarin in male mice. Pharm Biol 2015; 53(5): 739-45.
Hirayama K, Oshima H, Yamashita A, et al. Neuroprotective effects of silymarin on ischemia-induced delayed neuronal cell death in rat hippocampus. Brain Res 2016; 1646: 297-303.
Darvishi Khezri H, Salehifar E, Kosaryan M, et al. Potential effects of silymarin and its flavonolignan components in patients with β-thalassemia major: a comprehensive review in 2015. Adv Pharmacol Sci 2016; 3046373.
Razavi BM. Protective effect of silymarin against chemical-induced cardiotoxicity. Iran J Basic Med Sci 2016; 19(9): 916-23.
Lee JS, Hong DY, Kim ES, et al. Improving the water solubility and antimicrobial activity of silymarin by nanoencapsulation. Colloids Surf B Biointerfaces 2017; 154: 171-7.
Panapisal V, Charoensri S, Tantituvanont A. Formulation of microemulsion systems for dermal delivery of silymarin. AAPS PharmSciTech 2012; 13(2): 389-99.
Polachi N, Bai G, Li T, et al. Modulatory effects of silibinin in various cell signaling pathways against liver disorders and cancer - A comprehensive review. Eur J Med Chem 2016; 123: 577-95.
Li LH, Wu LJ, Tashiro S, et al. Silibinin prevents UV-induced HaCaT cell apoptosis partly through inhibition of caspase-8 pathway. Biol Pharm Bull 2006; 29(6): 1096-101.
Narayanapillai S, Agarwal C, Tilley C, et al. Silibinin is a potent sensitizer of UVA radiation-induced oxidative stress and apoptosis in human keratinocyte HaCaT cells. Photochem Photobiol 2012; 88(5): 1135-40.
Zheng N, Liu L, Liu WW, et al. Crosstalk of ROS/RNS and autophagy in silibinin-induced apoptosis of MCF-7 human breast cancer cells in vitro. Acta Pharmacol Sin 2017; 38(2): 277-89.
Raina K, Kumar S, Dhar D, et al. Silibinin and colorectal cancer chemoprevention: a comprehensive review on mechanisms and efficacy. J Biomed Res 2016; 30(6): 452-65.
Chen PN, Hsieh YS, Chiang CL, et al. Silibinin inhibits invasion of oral cancer cells by suppressing the MAPK pathway. J Dent Res 2006; 85(3): 220-5.
Anestopoulos I, Sfakianos AP, Franco R, et al. A novel role of silibinin as a putative epigenetic modulator in human prostate carcinoma. Molecules 2016; 22(1): E62.
De Zi X, Feyes D, Agarwal R. Anti-carcinogenic 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 cyclin. Clin Cancer Res 1998; 4(4): 1055-64. Deep G, Agarwal R. Antimetastatic efficacy of silibinin: molecular mechanisms and therapeutic potential against cancer. Cancer Metastasis Rev 2010; 29(3): 447-63.
DE Oliveira DT, Savio AL, Marcondes JP, et al.Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status. J Biosci 2017; 42(1): 91-101.
Bosch-Barrera J, Sais E, Cañete N, et al. Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin. Oncotarget 2016; 7(22): 32006-14.
Zhang B, Wang B, Cao S, et al. Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation. Int J Mol Med 2017; 39(5): 1111-8.
DebRoy S, Hiraga N, Imamura M, et al.Hepatitis C virus dynamics and cellular gene expression in uPA-SCID chimeric mice with humanized livers during intravenous silibinin monotherapy. J Viral Hepat 2016; 23(9): 708-17.
Song X, Zhou B, Zhang P, et al. Protective Effect of silibinin on learning and memory impairment in LPS-treated rats via ROS-BDNF-TrkB pathway. Neurochem Res 2016; 41(7): 1662-72.
Bouderba S, Sanchez-Martin C, Villanueva GR, et al. Beneficial effects of silibinin against the progression of metabolic syndrome, increased oxidative stress, and liver steatosis in Psammomys obesus, a relevant animal model of human obesity and diabetes. J Diabetes 2014; 6(2): 184-92.
Song X, Zhou B, Cui L, et al. Silibinin ameliorates Aβ25-35-induced memory deficits in rats by modulating autophagy and attenuating neuroinflammation as well as oxidative stress. Neurochem Res 2017; 42(4): 1073-83.
Kyriakopoulos G, Tsaroucha AK, Valsami G, et al. Silibinin improves TNF-α and M30 expression and histological parameters in rat kidneys after hepatic ischemia/reperfusion. J Invest Surg 2017; 18: 1-9.
Kim SH, Kim KY, Yu SN, et al. Silibinin induces mitochondrial NOX4-mediated endoplasmic reticulum stress response and its subsequent apoptosis. BMC Cancer 2016; 16: 452.
Harati K, Behr B, Wallner C, et al. Antiproliferative activity of epigallocatechin-3-gallate and silibinin on soft tissue sarcoma cells. Mol Med Rep 2017; 15(1): 103-10.
Ko JW, Shin NR, Park SH, et al. Silibinin inhibits the fibrotic responses induced by cigarette smoke via suppression of TGF- 1/Smad 2/3 signaling. Food Chem Toxicol 2017. 106(Pt A): 424- 9.
Nguyen MH, Yu H, Dong B. A supersaturating delivery system of silibinin exhibiting high payload achieved by amorphous nano-complexation with chitosan. Eur J Pharm Sci 2016; 89: 163-71.
Lee DY. Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J Nat Prod 2003; 66(9): 1171-4.
Zhou J, Chao G, Li Y, et al. Activation of NRF2/ARE by isosilybin alleviates Aβ25-35-induced oxidative stress injury in HT-22 cells. Neurosci Lett 2016; 632: 92-7.
McDonald BR, Nibbs AE, Scheidt KA. A biomimetic strategy to access the silybins: total synthesis of (-)-isosilybin A. Org Lett 2015; 17(1): 98-101.
Sy-Cordero AA, Day CS, Oberlies NH. Absolute configuration of isosilybin A by X-ray crystallography of the heavy atom analogue 7-(4-Bromobenzoyl)isosilybin A. J Nat Prod 2012; 75(11): 1879-81.
Pferschy-Wenzig EM, Atanasov AG, Malainer C, et al. Identification of isosilybin a from milk thistle seeds as an agonist of peroxisome proliferator-activated receptor gamma. J Nat Prod 2014; 77(4): 842-7.
Deep G, Gangar SC, Oberlies NH, et al. Isosilybin A induces apoptosis in human prostate cancer cells via targeting Akt, NF-κB, and androgen receptor signaling. Mol Carcinog 2010; 49(10): 902-12.
Sy-Cordero AA, Graf TN, Runyon SP, et al. Enhanced bioactivity of silybin B methylation products. Bioorg Med Chem 2013; 21(3): 742-7.
Deep G, Oberlies NH, Kroll DJ, et al. Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells. Carcinogenesis 2007; 28(7): 1533-42.
Deep G, Oberlies NH, Kroll DJ, et al. Isosilybin B causes androgen receptor degradation in human prostate carcinoma cells via PI3K-Akt-Mdm2-mediated pathway. Oncogene 2008; 27(28): 3986-98.
Smith WA, Lauren DR, Burgess EJ, et al. A silychristin isomer and variation of flavonolignan levels in milk thistle (Silybum marianum) fruits. Planta Med 2005; 71(9): 877-80.
Zielińska-Przyjemska M. An in vitro study of the protective effect of the flavonoid silydianin against reactive oxygen species. Phytother Res 2006; 20(2): 115-9.
Nagy L, Kuki Á, Nagy T, et al. Collision-induced dissociation study of isosilychristin, a constituent of silymarin. Rapid Commun Mass Spectrom 2013; 27(12): 1413-6.
Ignatowicz E, Szaefer H, Zielińska M, et al. Silybin and silydianin diminish the oxidative metabolism of human polymorphonuclear neutrophils. Acta Biochim Pol 1997; 44(1): 127-9.
Koláčková P, Růžičková G, Gregor T, et al. Quick method (FT-NIR) for the determination of oil and major fatty acids content in whole achenes of milk thistle (Silybum marianum (L.) Gaertn.). J Sci Food Agric 2015; 95(11): 2264-70.
Fathi-Achachlouei B, Azadmard-Damirchi S. Milk thistle seed oil constituents from different varieties grown in Iran. J Am Oil Chem Soc 2009; 86(7): 643-9.
Mei L, Wang L, Li Q, et al. Comparison of acid degumming and enzymatic degumming process for Silybum marianum seed oil. J Sci Food Agric 2013; 93(11): 2822-8.
Zhu SY, Dong Y, Tu J, et al. Silybum marianum oil attenuates oxidative stress and ameliorates mitochondrial dysfunction in mice treated with D-galactose. Pharmacogn Mag 2014; 10(Suppl. 1): S92-9.
Hahn HJ, Jung HJ, Schrammek-Drusios MC, et al. Instrumental evaluation of anti-aging effects of cosmetic formulations containing palmitoyl peptides, Silybum marianum seed oil, vitamin E and other functional ingredients on aged human skin. Exp Ther Med 2016; 12(2): 1171-6.
Fehér P, Ujhelyi Z, Vecsernyés M, et al. Hepatoprotective effects of a self-micro emulsifying drug delivery system containing Silybum marianum native seed oil against experimentally induced liver injury. Pharmazie 2015; 70(4): 231-8.
Skottová N, Kazdová L, Oliyarnyk O, et al. Phenolics-rich extracts from Silybum marianum and Prunella vulgaris reduce a high-sucrose diet induced oxidative stress in hereditary hypertriglyceridemic rats. Pharmacol Res 2004; 50(2): 123-30.
Mhamdi B, Abbassi F, Smaoui A, et al. Fatty acids, essential oil and phenolics composition of Silybum marianum seeds and their antioxidant activities. Pak J Pharm Sci 2016; 29(3): 953-9.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 08 July, 2019
Page: [430 - 440]
Pages: 11
DOI: 10.2174/1573401314666180327155745
Price: $65

Article Metrics

PDF: 36
PRC: 1