Skip to content
2000
Volume 32, Issue 39
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Milk thistle compounds have recently gained attention for their potential role in cancer prevention and treatment. Despite most evidence reporting this property refers to and animal studies, milk thistle flavonoids may provide insightful suggestions about novel chemopreventive agents. This narrative review provides an overview of the current understanding of milk thistle's effects on cancer cells and highlights possible mechanisms of action. The active compounds in milk thistle mainly exhibit antioxidant and anti-inflammatory effects, which protect cells and enhance their survival responses, even inhibiting cancer development. In addition, the compounds possess immunomodulatory properties crucial in preventing cancer progression. Another important mechanism is the induction of apoptosis, promoting cancer cell death and inhibiting tumour growth. These compounds inhibit angiogenesis, preventing tumour growth and spread. Due to their potential to inhibit cancer progression, they modulate cell signalling pathways, including the MAPK and PI3K/Akt pathways, which are involved in cell growth and survival. Although current research is promising, it is crucial to address the current gaps in knowledge about milk thistle compounds in cancer prevention and treatment. Future studies should focus on rigorous clinical trials, dose optimization, mechanistic investigations, combination therapy approaches, and personalized medicine to maximize their potential. Basic experimental evidence can provide new clues to establish clinical trials to improve cancer care and reassure patients and healthcare professionals.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673371391250415105506
2025-05-06
2025-11-03
Loading full text...

Full text loading...

References

  1. SinghR.P. DhanalakshmiS. TyagiA.K. ChanD.C. AgarwalC. AgarwalR. Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factor-binding protein-3 levels.Cancer Res.200262113063306912036915
    [Google Scholar]
  2. DasS.K. VasudevanD.M. Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver.Indian J. Biochem. Biophys.200643530631117133738
    [Google Scholar]
  3. AlbahriG. BadranA. BakiA.Z. AlameM. HijaziA. DaouA. BaydounE. Potential anti-tumorigenic properties of diverse medicinal plants against the majority of common types of cancer.Pharmaceuticals202417557410.3390/ph1705057438794144
    [Google Scholar]
  4. ShandizF.A. KarimiG. DayyaniM. HosseiniS. ElyasiS. Evaluation of oral silymarin formulation efficacy in prevention of doxorubicin induced hepatotoxicity in patients with non-metastatic breast cancer.J. Oncol. Pharm. Pract.2024107815522412687781078155224126877810.1177/1078155224126877839110237
    [Google Scholar]
  5. KoláčkováP. RůžičkováG. GregorT. ŠišperováE. 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.201595112264227010.1002/jsfa.694525297972
    [Google Scholar]
  6. JaggiA.S. SinghN. Silymarin and its role in chronic diseases.Adv. Exp. Med. Biol.2016929254410.1007/978‑3‑319‑41342‑6_2
    [Google Scholar]
  7. LeeD.Y.W. LiuY. Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle).J. Nat. Prod.20036691171117410.1021/np030163b14510591
    [Google Scholar]
  8. SoleimaniV. DelghandiP.S. MoallemS.A. KarimiG. Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review.Phytother. Res.20193361627163810.1002/ptr.636131069872
    [Google Scholar]
  9. FenclovaM. Stranska-ZachariasovaM. BenesF. NovakovaA. JonatovaP. KrenV. VitekL. HajslovaJ. Liquid chromatography–drift tube ion mobility–mass spectrometry as a new challenging tool for the separation and characterization of silymarin flavonolignans.Anal. Bioanal. Chem.2020412481983210.1007/s00216‑019‑02274‑331919606
    [Google Scholar]
  10. AbenavoliL. CapassoR. MilicN. CapassoF. Milk thistle in liver diseases: Past, present, future.Phytother. Res.201024101423143210.1002/ptr.320720564545
    [Google Scholar]
  11. NawazA. ZaibS. KhanI. AhmedA. ShahzadiK. RiazH. Silybum marianum : An overview of its phytochemistry and pharmacological activities with emphasis on potential anticancer properties.Anticancer Agents Med. Chem.202323131519153410.2174/1871520623666230412111152
    [Google Scholar]
  12. GhodousiM. KarbasforooshanH. ArabiL. ElyasiS. Silymarin as a preventive or therapeutic measure for chemotherapy and radiotherapy-induced adverse reactions: A comprehensive review of preclinical and clinical data.Eur. J. Clin. Pharmacol.2023791153810.1007/s00228‑022‑03434‑836450892
    [Google Scholar]
  13. EtemadiT. MomeniH.R. DarbandiN. AbnosiM.H. Silymarin modulates cadmium-induced oxidative stress in human spermatozoa.Andrologia2022548e1447510.1111/and.1447535640054
    [Google Scholar]
  14. SchönfeldV. WeisbrodB. MüllerM. Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity.Cell. Mol. Life Sci. 202253(11-1291792010.1007/s0001800501119447243
    [Google Scholar]
  15. LiakopoulouC. KazazisC. VallianouN.G. Silimarin and cancer.Anticancer Agents Med. Chem.201818141970197410.2174/1871520618666180905154949
    [Google Scholar]
  16. ZiX. AgarwalR. Silibinin decreases prostate-specific antigen with cell growth inhibition via G 1 arrest, leading to differentiation of prostate carcinoma cells: Implications for prostate cancer intervention.Proc. Natl. Acad. Sci. USA199996137490749510.1073/pnas.96.13.749010377442
    [Google Scholar]
  17. KoltaiT. FliegelL. Role of silymarin in cancer treatment: Facts, hypotheses, and questions.J. Evid. Based Integr. Med.2022272515690X21106882610.1177/2515690X211068826
    [Google Scholar]
  18. DuanL. CarrierD.J. ClausenE.C. Silymarin Extraction from Milk Thistle Using Hot WateProceedings of the Twenty-Fifth Symposium on Biotechnology for Fuels and Chemicals, Breckenridge, CO, May 4-7, 2003; Finkelstein, M.; McMillan, J.D.; Davison, B.H.; Evans, B., Eds.; Biotechnology for Fuels and Chemicals. Humana Press, Totowa, NJ, USA200455956810.1007/978‑1‑59259‑837‑3_46
    [Google Scholar]
  19. LiuL. ZhangH. Milk thistle oil extracted by enzyme-mediated assisted solvent extraction compared with n-hexane and cold-pressed extraction.Molecules2023286259110.3390/molecules2806259136985564
    [Google Scholar]
  20. XuC. YuanY. PangP. YangH. ZhangQ. YuanD. QiW. Urinary excretion of silibinin diastereoisomers and their conjugated metabolites in rat and human at different dosages.Biomed. Chromatogr.20223612e548010.1002/bmc.548035962523
    [Google Scholar]
  21. KarimiG. VahabzadehM. LariP. RashediniaM. MoshiriM. “Silymarin”, a promising pharmacological agent for treatment of diseases.Iran. J. Basic Med. Sci.201114430831723492971
    [Google Scholar]
  22. BrindaB.J. ZhuH.J. MarkowitzJ.S. A sensitive LC–MS/MS assay for the simultaneous analysis of the major active components of silymarin in human plasma.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.20129021910.1016/j.jchromb.2012.06.00322766231
    [Google Scholar]
  23. KatiyarS. Silymarin and skin cancer prevention: Anti-inflammatory, antioxidant and immunomodulatory effects (Review).Int. J. Oncol.200526116917610.3892/ijo.26.1.16915586237
    [Google Scholar]
  24. Imai-SumidaM. ChiyomaruT. MajidS. SainiS. NipH. DahiyaR. TanakaY. YamamuraS. Silibinin suppresses bladder cancer through down-regulation of actin cytoskeleton and PI3K/Akt signaling pathways.Oncotarget2017854920329204210.18632/oncotarget.2073429190895
    [Google Scholar]
  25. KalinowskaM. PłońskaA. TrusiakM. GołębiewskaE. Gorlewska-PietluszenkoA. Comparing the extraction methods, chemical composition, phenolic contents and antioxidant activity of edible oils from Cannabis sativa and Silybum marianu seeds.Sci. Rep.20221212060910.1038/s41598‑022‑25030‑736446937
    [Google Scholar]
  26. OliveiraD.D.T. SávioA.L.V. MarcondesC.D.J.P. BarrosT.M. BarbosaL.C. SalvadoriD.M.F. SilvaD.G.N. Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status.J. Biosci.20174219110110.1007/s12038‑016‑9654‑528229968
    [Google Scholar]
  27. AghemoA. AlekseevaO.P. AngelicoF. BakulinI.G. BakulinaN.V. BordinD. BueverovA.O. DrapkinaO.M. GillessenA. KagarmanovaE.M. KorochanskayaN.V. KucheryaviiU.A. LazebnikL.B. LivzanM.A. MaevI.V. MartynovA.I. OsipenkoM.F. SasE.I. StarodubovaA. UspenskyY.P. VinnitskayaE.V. YakovenkoE.P. YakovlevA.A. Role of silymarin as antioxidant in clinical management of chronic liver diseases: A narrative review.Ann. Med.20225411548156010.1080/07853890.2022.206985435635048
    [Google Scholar]
  28. VeisiS. JohariS.A. TylerC.R. MansouriB. EsmaeilbeigiM. Antioxidant properties of dietary supplements of free and nanoencapsulated silymarin and their ameliorative effects on silver nanoparticles induced oxidative stress in Nile tilapia (Oreochromis niloticus).Environ. Sci. Pollut. Res. Int.20212820260552606310.1007/s11356‑021‑12568‑833483926
    [Google Scholar]
  29. DeepG. OberliesN.H. KrollD.J. AgarwalR. Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells.Int. J. Cancer20081231415010.1002/ijc.2348518435416
    [Google Scholar]
  30. DhanalakshmiS. AgarwalC. SinghR.P. AgarwalR. Silibinin up-regulates DNA-protein kinase-dependent p53 activation to enhance UVB-induced apoptosis in mouse epithelial JB6 cells.J. Biol. Chem.200528021203752038310.1074/jbc.M41464020015792956
    [Google Scholar]
  31. KaurM. AgarwalR. Silymarin and epithelial cancer chemoprevention: How close we are to bedside?Toxicol. Appl. Pharmacol.2007224335035910.1016/j.taap.2006.11.01117184801
    [Google Scholar]
  32. ScavoM.P. GentileE. WolframJ. GuJ. BaroneM. EvangelopoulosM. MartinezJ.O. LiuX. CeliaC. TasciottiE. VilarE. ShenH. Multistage vector delivery of sulindac and silymarin for prevention of colon cancer.Colloids Surf. B Biointerfaces201513669470310.1016/j.colsurfb.2015.10.00526513752
    [Google Scholar]
  33. AlzoubiH.K. KhabourF.O. AlkofahiS.A. MhaidatM.N. Abu-SiniyehA.A. Anticancer and antimutagenic activity of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. against skin cancer induced by DMBA: In vitro and in vivo models.Pak. J. Pharm. Sci.202134398799334602423
    [Google Scholar]
  34. KhazaeiR. SeidaviA. BouyehM. A review on the mechanisms of the effect of silymarin in milk thistle ( Silybum marianum ) on some laboratory animals.Vet. Med. Sci.20228128930110.1002/vms3.64134599793
    [Google Scholar]
  35. ForghaniP. KhorramizadehM.R. WallerE.K. Silibinin inhibits accumulation of myeloid-derived suppressor cells and tumor growth of murine breast cancer.Cancer Med.20143221522410.1002/cam4.18624574320
    [Google Scholar]
  36. IslamA. MishraA. SiddiquiM.A. SiddiquieS. Recapitulation of evidence of phytochemical, pharmacokinetic and biomedical application of silybin.Drug Res.202171948950310.1055/a‑1528‑272134318464
    [Google Scholar]
  37. BoukazoulaF. AyariD. Effect of milk thistle ( Silybum marianum ) supplementation on the serum levels of oxidative stress markers in male half marathon athletes.Biomarkers202227546146910.1080/1354750X.2022.205692135315713
    [Google Scholar]
  38. ShankarV.K. PoliceA. AjjarapuS. MurthyS.N. Development of silymarin topical formulation: In vitro and ex vivo dermal kinetics of silymarin.Int. J. Pharm.202363012243110.1016/j.ijpharm.2022.12243136436747
    [Google Scholar]
  39. DelmasD. XiaoJ. VejuxA. AiresV. Silymarin and cancer: A dual strategy in both in chemoprevention and chemosensitivity.Molecules2020259200910.3390/molecules2509200932344919
    [Google Scholar]
  40. KacarS. AykanatB.N.E. SahinturkV. Silymarin inhibited DU145 cells by activating SLIT2 protein and suppressing expression of CXCR4.Med. Oncol.20203731810.1007/s12032‑020‑1343‑432062757
    [Google Scholar]
  41. StolfA.M. CardosoC.C. MoraisH. Alves de SouzaC.E. LombaL.A. BrandtA.P. AgnesJ.P. CollereF.C. GalindoC.M. CorsoC.R. SpercoskiK.M. DittrichL.R. ZampronioA.R. CadenaS.M.S.C. AccoA. Effects of silymarin on angiogenesis and oxidative stress in streptozotocin-induced diabetes in mice.Biomed. Pharmacother.201810823224310.1016/j.biopha.2018.09.04230219681
    [Google Scholar]
  42. MateenS. RainaK. AgarwalC. ChanD. AgarwalR. Silibinin synergizes with histone deacetylase and DNA methyltransferase inhibitors in upregulating E-cadherin expression together with inhibition of migration and invasion of human non-small cell lung cancer cells.J. Pharmacol. Exp. Ther.2013345220621410.1124/jpet.113.20347123461975
    [Google Scholar]
  43. DadarM. ShahaliY. ChakrabortyS. PrasadM. TahooriF. TiwariR. DhamaK. Antiinflammatory peptides: Current knowledge and promising prospects.Inflamm. Res.201968212514510.1007/s00011‑018‑1208‑x30560372
    [Google Scholar]
  44. El-KamaryS.S. ShardellM.D. Abdel-HamidM. IsmailS. El-AteekM. MetwallyM. MikhailN. HashemM. MousaA. Aboul-FotouhA. El-KassasM. EsmatG. StricklandG.T. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis.Phytomedicine200916539140010.1016/j.phymed.2009.02.00219303273
    [Google Scholar]
  45. SuraiP.F. SuraiA. Earle-PayneK. Silymarin and inflammation: Food for thoughts.Antioxidants20241319810.3390/antiox1301009838247522
    [Google Scholar]
  46. Katiyar KatiyarS.K. Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.) (Review).Int. J. Oncol.20103651053106010.3892/ijo_0000058620372777
    [Google Scholar]
  47. HuX. QinN. XueJ. LiS. HuangX. SunJ. XuF. LiZ. LiD. HuaH. Dehydrodiconiferyl alcohol from Silybum marianum (L.) Gaertn accelerates wound healing via inactivating NF-κB pathways in macrophages.J. Pharm. Pharmacol.202072230531710.1111/jphp.1320531742713
    [Google Scholar]
  48. KimS. OhD.S. OhJ. SonT. YukD. JungY.S. Silymarin prevents restraint stress-induced acute liver injury by ameliorating oxidative stress and reducing inflammatory response.Molecules201621444310.3390/molecules2104044327043523
    [Google Scholar]
  49. HohC. BoocockD. MarczyloT. SinghR. BerryD.P. DennisonA.R. HemingwayD. MillerA. WestK. EudenS. GarceaG. FarmerP.B. StewardW.P. GescherA.J. Pilot study of oral silibinin, a putative chemopreventive agent, in colorectal cancer patients: Silibinin levels in plasma, colorectum, and liver and their pharmacodynamic consequences.Clin. Cancer Res.20061292944295010.1158/1078‑0432.CCR‑05‑272416675592
    [Google Scholar]
  50. ComelliM.C. MengsU. SchneiderC. ProsdocimiM. Toward the definition of the mechanism of action of silymarin: Activities related to cellular protection from toxic damage induced by chemotherapy.Integr. Cancer Ther.20076212012910.1177/153473540730234917548791
    [Google Scholar]
  51. ShahidiM. VaziriF. HaerianA. FarzaneganA. JafariS. SharifiR. ShiraziF.S. Proliferative and anti-inflammatory effects of resveratrol and silymarin on human gingival fibroblasts: A view to the future.J. Dent.201714420321129285030
    [Google Scholar]
  52. MandegaryA. SaeediA. EftekhariA. MontazeriV. SharifE. Hepatoprotective effect of silyamarin in individuals chronically exposed to hydrogen sulfide; modulating influence of TNF-α cytokine genetic polymorphism.Daru20132112810.1186/2008‑2231‑21‑2823566372
    [Google Scholar]
  53. KřenV. WalterováD. Silybin and silymarin--new effects and applications.Biomed. Pap. Med. Fac. Univ. Palacky. Olomouc. Czech. Repub.20051491294110.5507/bp.2005.002
    [Google Scholar]
  54. RamakrishnanG. JaganS. KamarajS. AnandakumarP. DevakiT. Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteinases-2 and 9 in rat liver carcinogenesis.Invest. New Drugs200927323324010.1007/s10637‑008‑9163‑y18665326
    [Google Scholar]
  55. MurataN. MurakamiK. OzawaY. KinoshitaN. IrieK. ShirasawaT. ShimizuT. Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer’s disease mouse model.Biosci. Biotechnol. Biochem.201074112299230610.1271/bbb.10052421071836
    [Google Scholar]
  56. GheybiF. RajabianF. Tayarani-NajaranZ. AdibiA.R. AlavizadehS.H. KesharwaniP. SahebkarA. Liposomal silymarin anti-oxidative and anti-apoptotic features in lung cells: An implication in cadmium toxicity.J. Trace Elem. Med. Biol.20238012729110.1016/j.jtemb.2023.12729137672872
    [Google Scholar]
  57. FallahM. DavoodvandiA. NikmanzarS. AghiliS. MirazimiS.M.A. AschnerM. RashidianA. HamblinM.R. ChamanaraM. NaghshN. MirzaeiH. Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer.Biomed. Pharmacother.202114211202410.1016/j.biopha.2021.11202434399200
    [Google Scholar]
  58. YunD.G. LeeD.G. Silibinin triggers yeast apoptosis related to mitochondrial Ca2+ influx in Candida albicans.Int. J. Biochem. Cell Biol.2016801910.1016/j.biocel.2016.09.00827639679
    [Google Scholar]
  59. PirouzpanahM.B. SabzichiM. PirouzpanahS. ChavoshiH. SamadiN. Silibilin-induces apoptosis in breast cancer cells by modulating p53, p21, Bak and Bcl-XL pathways.Asian Pac. J. Cancer Prev.20151652087209210.7314/APJCP.2015.16.5.208725773855
    [Google Scholar]
  60. AslanA. CanM.İ. Milk thistle impedes the development of carbontetrachloride-induced liver damage in rats through suppression of bcl-2 and regulating caspase pathway.Life Sci.20141171131810.1016/j.lfs.2014.09.00525305509
    [Google Scholar]
  61. ChoiE.S. OhS. JangB. YuH.J. ShinJ.A. ChoN.P. YangI.H. WonD.H. KwonH.J. HongS.D. ChoS.D. Silymarin and its active component silibinin act as novel therapeutic alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling cascade.Cell Oncol.201740323524610.1007/s13402‑017‑0318‑828401485
    [Google Scholar]
  62. Kropiwiec-DomańskaK. BabiczM. Kędzierska-MatysekM. Szyndler-NędzaM. SkrzypczakE. WolińskiB. Effect of milk thistle ( Silybum marianum ) supplementation on pork offal quality.Animals20221212152610.3390/ani1212152635739863
    [Google Scholar]
  63. MasodKhooyM.J. FarasatM. SalmiS.M. MirzaeiH. Combinatorial treatment with Silybum marianum essential oil enhances the therapeutic efficacy of a 5-fluorouracil base therapy for hepatocellular carcinoma.Phytother. Res.20233751968198510.1002/ptr.771636788749
    [Google Scholar]
  64. DeepG. GangarS.C. RajamanickamS. RainaK. GuM. AgarwalC. OberliesN.H. AgarwalR. Angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer: Targeting VEGF-VEGFR signaling.PLoS One201274e3463010.1371/journal.pone.003463022514647
    [Google Scholar]
  65. AddeoR. Silibinin: A New Opportunity for the Treatment of Brain Metastasis from Lung Cancer.J. Exp. Pharmacol.20211390190310.2147/JEP.S32687134611448
    [Google Scholar]
  66. WuK. NingZ. ZengJ. FanJ. ZhouJ. ZhangT. ZhangL. ChenY. GaoY. WangB. GuoP. LiL. WangX. HeD. Silibinin inhibits β-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial–mesenchymal transition and stemness.Cell. Signal.201325122625263310.1016/j.cellsig.2013.08.02824012496
    [Google Scholar]
  67. SinghR.P. DeepG. ChittezhathM. KaurM. Dwyer-NieldL.D. MalkinsonA.M. AgarwalR. Effect of silibinin on the growth and progression of primary lung tumors in mice.J. Natl. Cancer Inst.2006981284685510.1093/jnci/djj23116788158
    [Google Scholar]
  68. WuT. LiuW. GuoW. ZhuX. Silymarin suppressed lung cancer growth in mice via inhibiting myeloid-derived suppressor cells.Biomed. Pharmacother.20168146046710.1016/j.biopha.2016.04.03927261626
    [Google Scholar]
  69. AmerM.E. AmerM.A. OthmanA.I. ElsayedD.A. El-MissiryM.A. AmmarO.A. Silymarin inhibits the progression of Ehrlich solid tumor via targeting molecular pathways of cell death, proliferation, angiogenesis, and metastasis in female mice.Mol. Biol. Rep.20224964659467110.1007/s11033‑022‑07315‑235305227
    [Google Scholar]
  70. ChuS.C. ChiouH.L. ChenP.N. YangS.F. HsiehY.S. Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2.Mol. Carcinog.200440314314910.1002/mc.20018
    [Google Scholar]
  71. SinghR. AgarwalR. Prostate cancer prevention by silibinin.Curr. Cancer Drug Targets20044111110.2174/156800904348160514965263
    [Google Scholar]
  72. GharagozlooM. JafariS. EsmaeilN. JavidE.N. BagherpourB. RezaeiA. Immunosuppressive effect of silymarin on mitogen-activated protein kinase signalling pathway: The impact on T cell proliferation and cytokine production.Basic Clin. Pharmacol. Toxicol.2013113320921410.1111/bcpt.1208823701595
    [Google Scholar]
  73. PolyakS.J. MorishimaC. ShuhartM.C. WangC.C. LiuY. LeeD.Y.W. Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin.Gastroenterology200713251925193610.1053/j.gastro.2007.02.03817484885
    [Google Scholar]
  74. YassinN.Y.S. AbouZidS.F. El-KalaawyA.M. AliT.M. ElesawyB.H. AhmedO.M. Tackling of renal carcinogenesis in wistar rats by Silybum marianum total extract, silymarin, and silibinin via modulation of oxidative stress, apoptosis, Nrf2, PPAR γ, NF- κ B, and PI3K/Akt signaling pathways.Oxid. Med. Cell. Longev.202120211766516910.1155/2021/766516934630852
    [Google Scholar]
  75. MulrowC. LawrenceV. JacobsB. DennehyC. SappJ. RamirezG. AguilarC. MontgomeryK. MorbidoniL. ArterburnJ. In AHRQ evidence report summaries.United StatesAgency for Healthcare Research and Quality2000
    [Google Scholar]
  76. FedericoA. DallioM. LoguercioC. Silymarin/silybin and chronic liver disease: A marriage of many years.Molecules201722219110.3390/molecules2202019128125040
    [Google Scholar]
  77. YuL. LiT. ZhangH. MaZ. WuS. Silymarin suppresses proliferation of human hepatocellular carcinoma cells under hypoxia through downregulation of the HIF-1α/VEGF pathway.Am. J. Transl. Res.20231574521453237560243
    [Google Scholar]
  78. PiscitelliS.C. FormentiniE. BursteinA.H. AlfaroR. JagannathaS. FalloonJ. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers.Pharmacotherapy200222555155610.1592/phco.22.8.551.3320512013352
    [Google Scholar]
  79. JacobsB.P. DennehyC. RamirezG. SappJ. LawrenceV.A. Milk thistle for the treatment of liver disease.Am. J. Med.2002113650651510.1016/S0002‑9343(02)01244‑512427501
    [Google Scholar]
  80. DiCenzoR. SheltonM. JordanK. KovalC. ForrestA. ReichmanR. MorseG. Coadministration of milk thistle and indinavir in healthy subjects.Pharmacotherapy200323786687010.1592/phco.23.7.866.3272312885100
    [Google Scholar]
  81. GillessenA. SchmidtH.H.J. Silymarin as supportive treatment in liver diseases: A narrative review.Adv. Ther.20203741279130110.1007/s12325‑020‑01251‑y32065376
    [Google Scholar]
  82. MillsE. WilsonK. ClarkeM. FosterB. WalkerS. RachlisB. DeGrootN. MontoriV.M. GoldW. PhillipsE. MyersS. GallicanoK. Milk thistle and indinavir: A randomized controlled pharmacokinetics study and meta-analysis.Eur. J. Clin. Pharmacol.20056111710.1007/s00228‑004‑0843‑z15666173
    [Google Scholar]
  83. PradhanS.C. GirishC. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine.Indian J. Med. Res.2006124549150417213517
    [Google Scholar]
  84. SallerR. BrignoliR. MelzerJ. MeierR. An updated systematic review with meta-analysis for the clinical evidence of silymarin.Forsch. Komplementmed.200815192010.1159/000113648
    [Google Scholar]
  85. VidlarA. VostalovaJ. UlrichovaJ. StudentV. KrajicekM. VrbkovaJ. SimanekV. 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.2010154323924410.5507/bp.2010.03621048810
    [Google Scholar]
  86. WadhwaK. PahwaR. KumarM. KumarS. SharmaP.C. SinghG. VermaR. MittalV. SinghI. KaushikD. JeandetP. Mechanistic insights into the pharmacological significance of silymarin.Molecules20222716532710.3390/molecules2716532736014565
    [Google Scholar]
  87. PatelS. WaghelaB. ShahK. VaidyaF. MirzaS. PatelS. PathakC. RawalR. Silibinin, a natural blend in polytherapy formulation for targeting Cd44v6 expressing colon cancer stem cells.Sci. Rep.2018811698510.1038/s41598‑018‑35069‑030451890
    [Google Scholar]
  88. MarmouziI. BouyahyaA. EzzatS.M. JemliE.M. KharbachM. The food plant Silybum marianum (L.) Gaertn.: Phytochemistry, Ethnopharmacology and clinical evidence.J. Ethnopharmacol.202126511330310.1016/j.jep.2020.11330332877720
    [Google Scholar]
  89. KarbasforooshanH. HosseiniS. ElyasiS. PakdelF.A. KarimiG. Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial.Phytother. Res.201933237938610.1002/ptr.623130479044
    [Google Scholar]
  90. EsfahaniM.B.A.S. ReisiN. MirmoghtadaeiM. Evaluating the safety and efficacy of silymarin in β-thalassemia patients: A review.Hemoglobin2015392758010.3109/03630269.2014.100322425643967
    [Google Scholar]
  91. KimJ. LeeY.N. LeeJ. LeeS.G. KimH. ChoiY.S. DraelosZ.D. KimJ. Efficacy and safety of silymarin containing antioxidant serum as an adjuvant treatment of mild-to-moderate acne vulgaris: A prospective, open-label pilot study.J. Cosmet. Dermatol.202322256156810.1111/jocd.1543936204969
    [Google Scholar]
  92. SiegelA.B. NarayanR. RodriguezR. GoyalA. JacobsonJ.S. KellyK. LadasE. LunghoferP.J. HansenR.J. GustafsonD.L. FlaigT.W. TsaiW.Y. WuD.P. LeeV. GreenleeH. A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma.Integr. Cancer Ther.2014131465310.1177/153473541349079823757319
    [Google Scholar]
  93. FlaigT.W. GlodéM. GustafsonD. BokhovenV.A. TaoY. WilsonS. SuL.J. LiY. HarrisonG. AgarwalR. CrawfordE.D. LuciaM.S. PollakM. A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer.Prostate201070884885510.1002/pros.2111820127732
    [Google Scholar]
  94. TamayoC. DiamondS. Review of clinical trials evaluating safety and efficacy of milk thistle ( Silybum marianum [L.] Gaertn.).Integr. Cancer Ther.20076214615710.1177/153473540730194217548793
    [Google Scholar]
  95. HackettE.S. MamaK.R. TwedtD.C. GustafsonD.L. Pharmacokinetics and safety of silibinin in horses.Am. J. Vet. Res.201374101327133210.2460/ajvr.74.10.132724066917
    [Google Scholar]
  96. WuJ.W. LinL.C. TsaiT.H. Drug–drug interactions of silymarin on the perspective of pharmacokinetics.J. Ethnopharmacol.2009121218519310.1016/j.jep.2008.10.03619041708
    [Google Scholar]
  97. FenclovaM. NovakovaA. ViktorovaJ. JonatovaP. DzumanZ. RumlT. KrenV. HajslovaJ. VitekL. Stranska-ZachariasovaM. Poor chemical and microbiological quality of the commercial milk thistle-based dietary supplements may account for their reported unsatisfactory and non-reproducible clinical outcomes.Sci. Rep.2019911111810.1038/s41598‑019‑47250‑031366891
    [Google Scholar]
  98. BrantleyS.J. GrafT.N. OberliesN.H. PaineM.F. A systematic approach to evaluate herb-drug interaction mechanisms: Investigation of milk thistle extracts and eight isolated constituents as CYP3A inhibitors.Drug Metab. Dispos.20134191662167010.1124/dmd.113.05256323801821
    [Google Scholar]
  99. ZiX. ZhangJ. AgarwalR. PollakM. Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells.Cancer Res.200060205617562011059749
    [Google Scholar]
  100. PickovaD. OstryV. TomanJ. MalirF. Presence of mycotoxins in milk thistle ( Silybum marianum ) food supplements: A review.Toxins2020121278210.3390/toxins1212078233302488
    [Google Scholar]
  101. ChenP.N. HsiehY.S. ChiouH.L. ChuS.C. Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways.Chem. Biol. Interact.20051562-314115010.1016/j.cbi.2005.08.00516169542
    [Google Scholar]
  102. Kawaguchi-SuzukiM. FryeR.F. ZhuH.J. BrindaB.J. ChavinK.D. BernsteinH.J. MarkowitzJ.S. The effects of milk thistle ( Silybum marianum ) on human cytochrome P450 activity.Drug Metab. Dispos.201442101611161610.1124/dmd.114.05723225028567
    [Google Scholar]
  103. RamasamyK. AgarwalR. Multitargeted therapy of cancer by silymarin.Cancer Lett.2008269235236210.1016/j.canlet.2008.03.05318472213
    [Google Scholar]
  104. WangH. TsungA. MishraL. HuangH. Regulatory T cell: A double-edged sword from metabolic-dysfunction-associated steatohepatitis to hepatocellular carcinoma.EBioMedicine202410110503110.1016/j.ebiom.2024.10503138401419
    [Google Scholar]
  105. EmadiS.A. RahbardarG.M. MehriS. HosseinzadehH. A review of therapeutic potentials of milk thistle ( Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents.Iran. J. Basic Med. Sci.202225101166117636311193
    [Google Scholar]
  106. MombeiniM. SakiG. KhorsandiL. BavarsadN. Effects of silymarin-loaded nanoparticles on HT-29 human colon cancer cells.Medicina2018541110.3390/medicina54010001
    [Google Scholar]
  107. ChenL. WuT. FanR. QianY.S. LiuJ.F. BaiJ. ZhengB. LiuX.L. ZhengD. DuL.T. JiangG.Q. WangY.C. FanX.T. DengG.H. WangC.Y. ShenF. HuH.P. ZhangQ.Z. YeY.N. ZhangJ. GaoY.H. XiaJ. YanH.D. LiangM.F. YuY.L. SunF.M. GaoY.J. SunJ. ZhongC.X. WangY. WangH. KongF. ChenJ.M. WenH. WuB.M. WangC.X. WuL. HouJ.L. WangH.Y. Cell-free DNA testing for early hepatocellular carcinoma surveillance.EBioMedicine202410010496210.1016/j.ebiom.2023.10496238184937
    [Google Scholar]
  108. JiangF. ZhaoJ. SunJ. ChenW. ZhaoY. ZhouS. YuanS. TimofeevaM. LawP.J. LarssonS.C. ChenD. HoulstonR.S. DunlopM.G. TheodoratouE. LiX. Impact of ambient air pollution on colorectal cancer risk and survival: Insights from a prospective cohort and epigenetic Mendelian randomization study.EBioMedicine202410310512610.1016/j.ebiom.2024.10512638631091
    [Google Scholar]
  109. MayerK.É. MyersR.P. LeeS.S. Silymarin treatment of viral hepatitis: A systematic review.J. Viral Hepat.200512655956710.1111/j.1365‑2893.2005.00636.x16255756
    [Google Scholar]
  110. PapadimitriouN. QuC. HarrisonT.A. BeverA.M. MartinR.M. TsilidisK.K. NewcombP.A. ThibodeauS.N. NewtonC.C. UmC.Y. Obón-SantacanaM. MorenoV. BrennerH. MandicM. Chang-ClaudeJ. HoffmeisterM. PellattA.J. SchoenR.E. HarlidS. OginoS. UgaiT. BuchananD.D. LynchB.M. GruberS.B. CaoY. HsuL. HuygheJ.R. LinY. SteinfelderR.S. SunW. GuelpenV.B. ZaidiS.H. TolandA.E. BerndtS.I. HuangW.Y. AglagoE.K. DrewD.A. FrenchA.J. GeorgesonP. GiannakisM. HullarM. NowakJ.A. ThomasC.E. MarchandL.L. ChengI. GallingerS. JenkinsM.A. GunterM.J. CampbellP.T. PetersU. SongM. PhippsA.I. MurphyN. Body size and risk of colorectal cancer molecular defined subtypes and pathways: Mendelian randomization analyses.EBioMedicine202410110501010.1016/j.ebiom.2024.10501038350331
    [Google Scholar]
  111. LiuS. LanB. WangY. YangT. LiL. GeH. ZengC. XuB. QianH. MaF. Pyrotinib and trastuzumab combination treatment synergistically overcomes HER2 dependency in HER2-positive breast cancer: Insights from the PHILA trial.EBioMedicine202410910537910.1016/j.ebiom.2024.10537939368454
    [Google Scholar]
  112. BjørnstadO.V. CarrascoM. FinneK. ArdawatiaV. WingeI. AskelandC. ArnesJ.B. KnutsvikG. KleftogiannisD. PauloJ.A. AkslenL.A. VetheH. Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model.EBioMedicine202410810532510.1016/j.ebiom.2024.10532539232464
    [Google Scholar]
  113. DesaiT.A. HedmanÅ.K. DimitriouM. KopruluM. FigielS. YinW. JohanssonM. WattsE.L. AtkinsJ.R. SokolovA.V. SchiöthH.B. GunterM.J. TsilidisK.K. MartinR.M. PietznerM. LangenbergC. MillsI.G. LambA.D. MälarstigA. KeyT.J. TravisR.C. Smith-ByrneK. Identifying proteomic risk factors for overall, aggressive, and early onset prostate cancer using Mendelian Randomisation and tumour spatial transcriptomics.EBioMedicine202410510516810.1016/j.ebiom.2024.10516838878676
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673371391250415105506
Loading
/content/journals/cmc/10.2174/0109298673371391250415105506
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test