1. Altekruse SF, McGlynn KA, Dickie LA, Kleiner DE. Hepatocellular carcinoma confirmation, treatment, and survival in surveillance, epidemiology, and end results registries, 1992-2008. Hepatology 2012; 55: 476-482.
2. Angeli JP, Barcelos GR, Serpeloni JM, Barbosa F, Jr., Nersesyan A, Mantovani MS. Evaluation of the genotoxic and anti-genotoxic activities of silybin in human hepatoma cells (HepG2). Mutagenesis 2010; 25: 223-229.
3. Ansari D, Tingstedt B, Andersson B, Holmquist F, Sturesson C, Williamsson C, et al. Pancreatic cancer: yesterday, today and tomorrow. Future Oncol 2016; 12: 1929-1946.
4. Anwar S, Madkor HR, Ahmed N, Wagih ME. In vivo anticlastogenic effect of silymarin from milk thistle Silybum marianum L. Indian J Pharmacol 2018; 50:108-115.
5. Barros TMB, Lima APB, Almeida TC, da Silva GN. Inhibition of urinary bladder cancer cell proliferation by silibinin. Environ Mol Mutagen 2020; 61: 445-455.
6. Becker-Schiebe M, Mengs U, Schaefer M, Bulitta M, Hoffmann W. Topical use of a silymarin-based preparation to prevent radiodermatitis: results of a prospective study in breast cancer patients. Strahlenther Onkol 2011; 187: 485-491.
7. Bhatia N, Agarwal C, Agarwal R. Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells. Nutr Cancer 2001; 39: 292-299.
8. Bombardelli E, Korti F, inventors. Compositions for treatment of fatigue related to cancer. Russia patent RU2631612C2. 2017 Sep 25.
9. Bower JE. Cancer-related fatigue--mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 2014; 11: 597-609.
10. Brandon-Warner E, Eheim AL, Foureau DM, Walling TL, Schrum LW, McKillop IH. Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice. Cancer Lett 2012; 326: 88-95.
11. Brantley SJ, Oberlies NH, Kroll DJ, Paine MF. Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations. J Pharmacol Exp Ther 2010; 332: 1081-1087.
12. Chambers CS, Holečková V, Petrásková L, Biedermann D, Valentová K, Buchta M, et al. The silymarin composition… and why does it matter??? Food Res Int 2017; 100: 339-353.
13. Chen CH, Huang TS, Wong CH, Hong CL, Tsai YH, Liang CC, et al. Synergistic anti-cancer effect of baicalein and silymarin on human hepatoma HepG2 Cells. Food Chem Toxicol 2009; 47: 638-644.
14. Chevreau N, inventor; LIFEVANTAGE Corp, assignee. Topical compositions and methods for reducing oxidative stress. United States patent US 20160166626A1. 2016 Jun 16.
15. Ciustea M, Ciustea G, inventors. Combination therapy and methods for treatment and prevention of hyperproliferative diseases. United States patent US 20130045179A1. 2013 Feb 21.
16. Claudio L, Massimo R, D’Amatoulrich M, Mengsralf-Tosten, French PP, inventors. Silibinin component for the treatment of hepatitis. Japan patent JP5349486B2. 2013 Nov 20.
17. Cornblatt B, Cornblatt G, Bzhelyansky A, Henderson RW, inventors. Compositions comprising sulforaphane or a sulforaphane precursor and a milk thistle extract or powder. Taiwan patent TW201402129A. 2014 Jan 16.
18. Deep G, Agarwal R. Chemopreventive efficacy of silymarin in skin and prostate cancer. Integr Cancer Ther 2007; 6: 130-145.
19. Fanoudi S, Alavi MS, Karimi G, Hosseinzadeh H. Milk thistle (Silybum marianum) as an antidote or a protective agent against natural or chemical toxicities: a review. Drug Chem Toxicol 2020; 43: 240-254.
20. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, et al. Cancer statistics for the year 2020: An overview. Int J Cancer 2021; 149: 778-789.
21. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127: 2893-2917.
22. Frassová Z, Rudá-Kučerová J. Milk thistle (Silybum marianum) as a Supportive Phytotherapeutic Agent in Oncology. Klin Onkol 2017; 30: 426-432.
23. García-Maceira P, Mateo J. Silibinin inhibits hypoxia-inducible factor-1alpha and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy. Oncogene 2009; 28: 313-324.
24. Ge Y, Zhang Y, Chen Y, Li Q, Chen J, Dong Y, et al. Silibinin causes apoptosis and cell cycle arrest in some human pancreatic cancer cells. Int J Mol Sci 2011; 12: 4861-4871.
25. Girardi B, Principi M, Pricci M, Giorgio F, Iannone A, Losurdo G, et al. Chemoprevention of inflammation-related colorectal cancer by silymarin-, acetyl-11-keto-beta-boswellic acid-, curcumin- and maltodextrin-enriched dietetic formulation in animal model. Carcinogenesis 2018; 39: 1274-1282.
26. Goral V. Pancreatic Cancer: Pathogenesis and Diagnosis. Asian Pac J Cancer Prev 2015; 16: 5619-5624.
27. Gorev V, Kostikov O, inventors. Three-component herbal formulation for the management of pre-diabetic and diabetic states, and liver diseases. Canada patent CA2983760A1. 2019 Apr 25.
28. Guseongdeug, inventor. Cosmetic composition containing Silymarin for the protection skin damage by air pollutants. South Korea patent KR101930311B1. 2018 Dec 18.
29. 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: 10-16.
30. Hosseini S, Rezaei S, Moghaddam MRN, Elyasi S, Karimi G. Evaluation of oral nano-silymarin formulation efficacy on prevention of radiotherapy induced mucositis: A randomized, double-blinded, placebo-controlled clinical trial. PharmaNutrition. 2021; 15: 100253.
31. Huang S, Huang S, Huang Y, inventors. A kind of Silybum marianum Gaertn Seed Oil solid beverage of relieving alcoholism and protecting liver and preparation method thereof. Chinese patent CN108419977A. 2018 Aug 21.
32. Hubertus J, Wolfgang W, Dana S-W, Michael PA, inventors. Combination prepration, particulary for treating prostate cancer. Germany patent EP1904018. 2008 Feb 04.
33. Ilic M, Ilic I. Epidemiology of pancreatic cancer. World J Gastroenterol 2016; 22: 9694-9705.
34. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61: 69-90.
35. Juan Z, inventorA kind of Baoganleifufang and preparation method thereof. China patent CN110025686A. 2019 Jul 19.
36. Kacar S, Bektur Aykanat NE, Sahinturk V. Silymarin inhibited DU145 cells by activating SLIT2 protein and suppressing expression of CXCR4. Med Oncol 2020; 37: 18.
37. Karbasforooshan H, Hosseini S, Elyasi S, Fani Pakdel A, Karimi G. Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial. Phytother Res 2019; 33: 379-386.
38. Kawaguchi-Suzuki M, Frye RF, Zhu HJ, Brinda BJ, Chavin KD, Bernstein HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos 2014; 42: 1611-1616.
39. Khan N, Afaq F, Mukhtar H. Cancer chemoprevention through dietary anti-oxidants: progress and promise. Anti-oxid Redox Signal 2008; 10: 475-510.
40. Khodadoust M, Sharma A, Bruening R, inventors; Bionaut Pharmaceuticals Inc, assignee. Pancreatic cancer treatment using Na+/K+ ATPase inhibitors. United States patent US 20070105790A1. 2007 May 10.
41. Kim MJ, Kim DU, Choi JW, Kim DG, Song HJ, Bae GS, et al. Silymarin attenuates the severity of cerulein-induced acute pancreatitis. Pancreas 2020; 49: 89-95.
42. Kim SH, Choo GS, Yoo ES, Woo JS, Han SH, Lee JH, et al. Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells. Oncol Rep 2019; 42: 1904-1914.
43. Koo C-h, Lee Y-c, inventors. Composition for protecting hepatocyte containing silymarin and lipoic acid or its salts. South Korea patent KR100693613B1. 2007-03-14.
44. LAMBERT R, inventorTreatment for pancreatic adenocarcinoma and other cancers of epithelial origin. WIPO (PCT) patent WO2012122295A2. 2012 Sep 13.
45. Li CC, Hsiang CY, Wu SL, Ho TY. Identification of novel mechanisms of silymarin on the carbon tetrachloride-induced liver fibrosis in mice by nuclear factor-κB bioluminescent imaging-guided transcriptomic analysis. Food Chem Toxicol 2012; 50: 1568-1575.
46. Li R, Yu J, Wang C. Silibinin promotes the apoptosis of gastric cancer BGC823 cells through caspase pathway. J BUON 2017; 22: 1148-1153.
47. Lim KS, Ahn YT, Kim YH, Bae JS, Oh HK, Huh CS, inventors. Composition for the improvement of liver function, the reduction of serum ethanol level and anti-oxidant activity enhancement. United States patent US 7544356B2. 2009 Jun 09.
48. Lu W, Lin C, King TD, Chen H, Reynolds RC, Li Y. Silibinin inhibits Wnt/β-catenin signaling by suppressing Wnt co-receptor LRP6 expression in human prostate and breast cancer cells. Cell Signal 2012; 24: 2291-2296.
49. Mastron JK, Siveen KS, Sethi G, Bishayee A. Silymarin and hepatocellular carcinoma: A systematic, comprehensive, and critical review. Anticancer Drugs 2015; 26: 475-486.
50. Matsuda T, Ferreri K, Todorov I, Kuroda Y, Smith CV, Kandeel F, et al. Silymarin Protects Pancreatic β-Cells against Cytokine- Mediated Toxicity: Implication of c-Jun NH2-terminal kinase and Janus kinase/signal transducer and activator of transcription Pathways. Endocrinology 2005; 146: 175-185.
51. McCord JM, Myhill PR, inventors. Compositions for alleviating inflammation and oxidative stress in a mammal. United States patent US 9265808B2. 2016 Jan 23.
52. Mehri S, Dadesh Q, Tabeshpour J, Vahdati Hassani F, Karimi G, Hosseinzadeh H. Evaluation of the neuroprotective effect of silymarin on acrylamide-induced neurotoxicity. Jundishapur J Nat Pharm Prod. 2016; 11: e37644.
53. Mehri S, Omar Rawas Y, Vahdati Hassani F, Karimi G, Hosseinzadeh H. Evaluation of the Neuroprotective effect of Silybum marianum extract on acrylamide-induced neurotoxicity: an in vitro and in vivo study. J North Khor Uni Med Sci 2018; 10(1): 46-52.
54. Moezian G, Javadinia S, Sales S, Fanipakdel A, Elyasi S, Karimi G. Oral silymarin formulation efficacy in management of AC-T protocol induced hepatotoxicity in breast cancer patients: A randomized, triple blind, placebo-controlled clinical trial. J Oncol Pharm Pract 2022; 28: 827-835.
55. Mokhtari MJ, Motamed N, Shokrgozar MA. Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line. Cell Biol Int. 2008; 32: 888-892.
56. Moore A, Donahue T. Pancreatic Cancer. JAMA. 2019; 322: 1426.
57. Morrison AH, Byrne KT, Vonderheide RH. Immunotherapy and prevention of pancreatic cancer. Trends Cancer 2018; 4: 418- 428.
58. Murad H, inventor. Compositions and methods for treating dermatological disorders. United States. patent US 20020127256A1. 2002 Sep 12.
59. Nambiar D, Prajapati V, Agarwal R, Singh RP. In vitro and in vivo anticancer efficacy of silibinin against human pancreatic cancer BxPC-3 and PANC-1 cells. Cancer Lett 2013; 334: 109-117.
60. Nambiar DK, Rajamani P, Singh RP. Silibinin attenuates ionizing radiation-induced pro-angiogenic response and EMT in prostate cancer cells. Biochem Biophys Res Commun 2015; 456: 262-268.
61. Neefjes EC, van der Vorst MJ, Blauwhoff-Buskermolen S, Verheul HM. Aiming for a better understanding and management of cancer-related fatigue. Oncologist 2013; 18: 1135-1143.
62. Neha, Jaggi AS, Singh N. Silymarin and Its Role in Chronic Diseases. Adv Exp Med Biol 2016; 929: 25-44.
63. Nishisgori C. Current concept of photocarcinogenesis. Photochem Photobiol Sci 2015; 14: 1713-1721.
64. Park JM, Lee HJ, Yoo JH, Ko WJ, Cho JY, Hahm KB. Overview of gastrointestinal cancer prevention in Asia. Best Pract Res Clin Gastroenterol 2015; 29: 855-867.
65. Pashaei-Asl F, Pashaei-Asl R, Khodadadi K, Akbarzadeh A, Ebrahimie E, Pashaiasl M. Enhancement of anticancer activity by silibinin and paclitaxel combination on the ovarian cancer. Artif Cells Nanomed Biotechnol 2018; 46: 1483-1487.
66. Pourová J, Applová L, Macáková K, Vopršalová M, Migkos T, Bentanachs R. The effect of silymarin flavonolignans and their sulfated conjugates on platelet aggregation and blood vessels ex vivo. Nutrients 2019; 11: 2286.
67. Program NT. Toxicology and carcinogenesis studies of milk thistle extract (CAS No. 84604-20-6) in F344/N rats and B6C3F1 mice (Feed Studies). Natl Toxicol Program Tech Rep Ser 2011(565): 1-177.
68. Ramakrishnan G, Augustine TA, Jagan S, Vinodhkumar R, Devaki T. Effect of silymarin on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Exp Oncol 2007; 29: 39-44.
69. Ramakrishnan G, Lo Muzio L, Elinos-Báez CM, Jagan S, Augustine TA, Kamaraj S, et al. Silymarin inhibited proliferation and induced apoptosis in hepatic cancer cells. Cell Prolif 2009; 42: 229-240.
70. Ramakrishnan G, Raghavendran HR, Vinodhkumar R, Devaki T. Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats. Chem Biol Interact 2006; 161: 104-114.
71. Rangel JO, inventor. Prostate disorder(s) phyto-nutraceutical synergistic composition. United States patent US 20080260771A1. 2008 Oct 23.
72. Roy S, Deep G, Agarwal C, Agarwal R. Silibinin prevents ultraviolet B radiation-induced epidermal damages in JB6 cells and mouse skin in a p53-GADD45α-dependent manner. Carcinogenesis 2012; 33: 629-636.
73. Shukla SK, Dasgupta A, Mehla K, Gunda V, Vernucci E, Souchek J, et al. Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth. Oncotarget 2015; 6: 41146-41161.
74. Si L, Fu J, Liu W, Hayashi T, Nie Y, Mizuno K, et al. Silibinin inhibits migration and invasion of breast cancer MDA-MB-231 cells through induction of mitochondrial fusion. Mol Cell Biochem 2020; 463: 189-201.
75. Smit F, Frisohageman R, Johann JF, inventors. Method for increasing glutathione present in cells. Japan patent JP2005520787A. 2005 July 14.
76. Soleimani V, Delghandi PS, Moallem SA, Karimi G. Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review. Phytother Res 2019; 33:1627-1638.
77. Stuckler F, inventor. Natural substances based agent. United States patent US 6605296B1. 2003 Aug 12.
78. Surh I, Rundhaug J, Pavone A, Mikulec C, Abel E, Fischer SM. Upregulation of the EP1 receptor for prostaglandin E2 promotes skin tumor progression. Mol Carcinog 2011; 50: 458-468.
79. Tajmohammadi A, Razavi BM, Hosseinzadeh H. Silybum marianum (milk thistle) and its main constituent, silymarin, as a potential therapeutic plant in metabolic syndrome: A review. Phytother Res 2018; 32: 1933-1949.
80. Tilley C, Deep G, Agarwal C, Wempe MF, Biedermann D, Valentová K, et al. Silibinin and its 2,3-dehydro-derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation. Mol Carcinog 2016; 55: 3-14.
81. Tooiserkani F, Hormati A, Moradi H, Ali asl F. A Glimpse of Silybum marianum from the perspective of Iranian traditional medicine and modern studies. Qom Univ Med Sci J 2019; 13: 78-86.
82. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87-108.
83. Tyagi AK, Singh RP, Agarwal C, Chan DC, Agarwal R. Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis. Clin Cancer Res 2002; 8: 3512-3519.
84. Vahabzadeh M, Amiri N, Karimi G. Effects of silymarin on metabolic syndrome: a review. J Sci Food Agric 2018; 98: 4816-4823.
85. Van Helvoort ALB, Norren KV, Hageman RJJ, Verwillegen WA, Lansink M, inventors. Anti-proliferative composition. European Patent Office. patent EP1448232B1. 2014 July 02.
86. Vidlar A, Vostalova J, Ulrichova J, Student V, Krajicek M, Vrbkova J, et al. The safety and efficacy of a silymarin and selenium combination in men after radical prostatectomy - a six month placebo-controlled double-blind clinical trial. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010; 154: 239-244.
87. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet 2011; 378: 607- 620.
88. Vostalova J, Vidlar A, Ulrichova J, Vrbkova J, Simanek V, Student V. Use of selenium-silymarin mix reduces lower urinary tract symptoms and prostate specific antigen in men. Phytomedicine 2013; 21: 75-81.
89. Wang H, Khor TO, Shu L, Su ZY, Fuentes F, Lee JH, et al. Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability. Anticancer Agents Med Chem 2012; 12: 1281-1305.
90. Xie Y, Zhang D, Zhang J, Yuan J. Metabolism, Transport and drug-drug interactions of silymarin. Molecules 2019; 24: 3693.
91. Yang LH, Xu HT, Han Y, Li QC, Liu Y, Zhao Y, et al. Axin downregulates TCF-4 transcription via beta-catenin, but not p53, and inhibits the proliferation and invasion of lung cancer cells. Mol Cancer. 2010; 9: 25.
92. Yingchang G, Peng Z, Shanshan S, inventors. Medicine for assisting interventional therapy of liver cancer. China patent CN106377627A. 2017 Feb 08.
93. Zabrecky G, inventor. Methods and formulations for treating chronic liver disease. United States patent US 20100086627A1. 2010 Apr 08.
94. Zhang X, Liu J, Zhang P, Dai L, Wu Z, Wang L, et al. Silibinin induces G1 arrest, apoptosis and JNK/SAPK upregulation in SW1990 human pancreatic cancer cells. Oncol Lett 2018; 15: 9868-9876.
95. Zi X, Grasso AW, Kung HJ, Agarwal R. A flavonoid anti-oxidant, silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells. Cancer Res 1998; 58: 1920-1929.