Summary: Heterodimers of FLAVONOIDS bound to LIGNANS.

Top Publications

  1. Shibano M, Lin A, Itokawa H, Lee K. Separation and characterization of active flavonolignans of Silybum marianum by liquid chromatography connected with hybrid ion-trap and time-of-flight mass spectrometry (LC-MS/IT-TOF). J Nat Prod. 2007;70:1424-8 pubmed
    ..A (1) and B (2), silydianin (3), silybins A (4) and B (5), and isosilybins A (6) and B (7) are major bioactive flavonolignans in silymarin, a herbal remedy derived from the milk thistle Silybum marianum...
  2. Polyak S, Morishima C, Lohmann V, Pal S, Lee D, Liu Y, et al. Identification of hepatoprotective flavonolignans from silymarin. Proc Natl Acad Sci U S A. 2010;107:5995-9 pubmed publisher
    ..In the current study, we evaluated the hepatoprotective actions of the seven major flavonolignans and one flavonoid that comprise silymarin...
  3. Miranda S, Lee J, Brouwer K, Wen Z, Smith P, Hawke R. Hepatic metabolism and biliary excretion of silymarin flavonolignans in isolated perfused rat livers: role of multidrug resistance-associated protein 2 (Abcc2). Drug Metab Dispos. 2008;36:2219-26 pubmed publisher
    ..Mrp2) (Abcc2) in the biliary excretion of silymarin, the hepatobiliary disposition of the six major silymarin flavonolignans was studied using isolated perfused livers (IPRLs) from wild-type (WT) and Mrp2-deficient (TR(-)) Wistar rats...
  4. Mohanlal S, Parvathy R, Shalini V, Helen A, Jayalekshmy A. Isolation, characterization and quantification of tricin and flavonolignans in the medicinal rice Njavara (Oryza sativa L.), as compared to staple varieties. Plant Foods Hum Nutr. 2011;66:91-6 pubmed publisher
    ..methanolic extract of Njavara Black (NB) rice bran gave three important compounds namely, tricin and two rare flavonolignans- tricin 4'-O-(erythro-?-guaiacylglyceryl) ether and tricin 4'-O-(threo-?-guaiacylglyceryl) ether...
  5. Chlopcíková S, Psotova J, Miketova P, Simanek V. Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part I. Silymarin and its flavonolignans. Phytother Res. 2004;18:107-10 pubmed
    ..The ability of silymarin complex and its components to protect cardiomyocytes against doxorubicin-induced oxidative stress is due mainly to their cell membrane stabilization effect, radical scavenging and iron chelating potency. ..
  6. Deep G, Gangar S, Rajamanickam S, Raina K, Gu M, Agarwal C, et al. Angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer: targeting VEGF-VEGFR signaling. PLoS ONE. 2012;7:e34630 pubmed publisher
    ..The rationale of the present study was to compare the anti-angiogenic potential of four pure diastereoisomeric flavonolignans, namely silybin A, silybin B, isosilybin A and isosilybin B, which we established previously as biologically ..
  7. Wenzig E, Kunert O, Ferreira D, Schmid M, Schühly W, Bauer R, et al. Flavonolignans from Avena sativa. J Nat Prod. 2005;68:289-92 pubmed
    Three flavonolignans derived from the flavone tricin were isolated from Avena sativa herb. This is the first report of the presence of flavonolignans in A. sativa...
  8. Chang C, Wang G, Zhang L, Tsai W, Chen R, Wu Y, et al. Cardiovascular protective flavonolignans and flavonoids from Calamus quiquesetinervius. Phytochemistry. 2010;71:271-9 pubmed publisher
    Tricin-type flavonolignans, (2S)-dihydrotricin 4'-O-(erythro-beta-guaiacylglyceryl) ether, (2S)-dihydrotricin 4'-O-(threo-beta-guaiacylglyceryl) ether, (2S)-dihydrotricin 4'-O-(threo-beta-4-hydroxyphenylglyceryl) ether, tricin 4'-O-(..
  9. Trouillas P, Marsal P, Svobodova A, Vostalova J, Gažák R, Hrbac J, et al. Mechanism of the antioxidant action of silybin and 2,3-dehydrosilybin flavonolignans: a joint experimental and theoretical study. J Phys Chem A. 2008;112:1054-63 pubmed publisher
    b>Flavonolignans from silymarin, the standardized plant extract obtained from thistle, exhibit various antioxidant activities, which correlate with the other biological and therapeutic properties of that extract...

More Information


  1. Svobodova A, Walterova D, Psotova J. Influence of silymarin and its flavonolignans on H(2)O(2)-induced oxidative stress in human keratinocytes and mouse fibroblasts. Burns. 2006;32:973-9 pubmed
    ..In this study, we investigated the protective effects of silymarin, its flavonolignans silybin and dehydrosilybin and flavonoids quercetin and taxifolin against hydrogen peroxide-induced damage to ..
  2. Davis Searles P, Nakanishi Y, Kim N, Graf T, Oberlies N, Wani M, et al. Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. Cancer Res. 2005;65:4448-57 pubmed
    ..Whereas several other more abundant flavonolignans do ultimately influence the same end points at higher exposure concentrations, these findings are suggestive ..
  3. Deep G, Oberlies N, Kroll D, Agarwal R. Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells. Int J Cancer. 2008;123:41-50 pubmed publisher
    ..This study provided further evidence for differential anticancer potential among each silymarin constituent, which would have potential implications in devising better formulations of silymarin against prostate and other cancers. ..
  4. Wang K, Zhang H, Shen L, Du Q, Li J. 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;53:1053-7 pubmed publisher
    ..A (1) and B (2), silydianin (3), silybins A (4) and B (5), and isosilybins A (6) and B (7), major bioactive flavonolignans in silymarin, a herbal remedy derived from the milk thistle Silybum marianum...
  5. Graf T, Wani M, Agarwal R, Kroll D, Oberlies N. Gram-scale purification of flavonolignan diastereoisomers from Silybum marianum (Milk Thistle) extract in support of preclinical in vivo studies for prostate cancer chemoprevention. Planta Med. 2007;73:1495-501 pubmed
    ..is a mixture of at least eight compounds, and four major constituents are a group of structurally related flavonolignans: silybin A, silybin B, isosilybin A, and isosilybin B...
  6. Althagafy H, Meza Avina M, Oberlies N, Croatt M. Mechanistic study of the biomimetic synthesis of flavonolignan diastereoisomers in milk thistle. J Org Chem. 2013;78:7594-600 pubmed publisher
    ..This mechanism is significantly different from a previously proposed process that involves the coupling of two independently formed radicals. ..
  7. Dunnick J, Singh B, Nyska A, Peckham J, Kissling G, Sanders J. Investigating the potential for toxicity from long-term use of the herbal products, goldenseal and milk thistle. Toxicol Pathol. 2011;39:398-409 pubmed publisher
    ..In contrast, the radical-scavenging and antioxidant properties of silibinin and other flavonolignans in milk thistle extract may have contributed to the decrease in background tumors in rodents in the present ..
  8. Esposito F, Tintori C, Martini R, Christ F, Debyser Z, Ferrarese R, et al. Kuwanon-L as a New Allosteric HIV-1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation. Chembiochem. 2015;16:2507-12 pubmed publisher
    ..Overall, docking and biochemical results suggest that kuwanon-L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents. ..
  9. Lee M, Kim W, Park H, Kang S, Lee S. Anti-proliferative activity of hydnocarpin, a natural lignan, is associated with the suppression of Wnt/?-catenin signaling pathway in colon cancer cells. Bioorg Med Chem Lett. 2013;23:5511-4 pubmed publisher
    ..These data suggest that hydnocarpin might be a novel Wnt inhibitor and has a potential of signaling regulator in ?-catenin-mediated signaling pathways. ..
  10. Colturato C, Constantin R, Maeda A, Constantin R, Yamamoto N, Bracht A, et al. Metabolic effects of silibinin in the rat liver. Chem Biol Interact. 2012;195:119-32 pubmed publisher
    ..However, this effect was, in part, secondary to impairment in cellular energy metabolism, a finding that should be considered in its therapeutic usage. ..
  11. Corchete P, Bru R. Proteome alterations monitored by DIGE analysis in Silybum marianum cell cultures elicited with methyl jasmonate and methyl B cyclodextrin. J Proteomics. 2013;85:99-108 pubmed publisher
    ..This finding forms a baseline for future research on a non-sequenced medicinal plant S. marianum at molecular level. ..
  12. Albassam A, Frye R, Markowitz J. The effect of milk thistle (Silybum marianum) and its main flavonolignans on CYP2C8 enzyme activity in human liver microsomes. Chem Biol Interact. 2017;271:24-29 pubmed publisher
    ..extract of milk thistle is termed silymarin, a complex mixture that contains a number of structurally-related flavonolignans, the flavonoid, taxifolin, and a number of other constituents...
  13. Zhao Y, Chen B, Yao S. 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;38:564-70 pubmed
    ..developed for simultaneous determination of multiple bioactive compounds such as abietane-type diterpenes, flavonolignans and phenolic compounds in compound preparations of Silybum marianum and Salvia miltiorrhiza...
  14. Nyiredy S, Samu Z, Szucs Z, Gulácsi K, Kurtan T, Antus S. New insight into the biosynthesis of flavanolignans in the white-flowered variant of Silybum marianum. J Chromatogr Sci. 2008;46:93-6 pubmed
    ..Moreover, the isolation of their cis-benzodioxane diastereomers, (-)-isocisilandrin (5) and cisilandrin (6), confirm that the previously proposed biosynthetic pathway involving a nonselective O-beta coupling is correct. ..
  15. Verschoyle R, Brown K, Steward W, Gescher A. Consumption of silibinin, a flavonolignan from milk thistle, and mammary cancer development in the C3(1) SV40 T,t antigen transgenic multiple mammary adenocarcinoma (TAg) mouse. Cancer Chemother Pharmacol. 2008;62:369-72 pubmed
    ..Intervention neither promoted, nor interfered with, tumour development. The result suggests that promotion of carcinogenesis is not a feature of silibinin consistent across rodent models of mammary carcinogenesis. ..
  16. Spiridonov A, Popov A, Kurkin V, Berezin I, Zinina M. [The use of flavolignans of "Silybum marianum (L.) Gaertn." to create a new fat product--fortified butter]. Vopr Pitan. 2005;74:42-5 pubmed
  17. Chai X, Lu Y, Ren H, Tu P. [Advances in studies on chemical constituents and bioactivities of plants from flacourtiaceae]. Zhongguo Zhong Yao Za Zhi. 2006;31:269-79 pubmed
  18. Kim J, Lau E, Pan L, de Blanco E. NF-kappaB inhibitors from Brucea javanica exhibiting intracellular effects on reactive oxygen species. Anticancer Res. 2010;30:3295-300 pubmed
    ..Brucea javanica was studied to identify nuclear factor kappaB (NF-?B) inhibitors exhibiting reactive oxygen species (ROS) intracellular amplification...
  19. Smith W, Lauren D, Burgess E, Perry N, Martin R. A silychristin isomer and variation of flavonolignan levels in milk thistle (Silybum marianum) fruits. Planta Med. 2005;71:877-80 pubmed
    ..This was shown by NMR spectroscopy to be silychristin B (8), a diastereoisomer of the known silychristin (7). Levels of these and the other flavonolignans varied markedly in fruits of different S. marianum samples.
  20. Košinová P, Gažák R, Duroux J, Lazzaroni R, Kren V, Assfeld X, et al. Dimerisation process of silybin-type flavonolignans: insights from theory. Chemphyschem. 2011;12:1135-42 pubmed publisher
    ..g., dehydrosilybin dimerisation after H-atom abstraction from the 3-OH group). This explains the regioselectivity of polyphenol dimerisation. ..
  21. Xiao X, Huang H, Ge Z, Rounge T, Shi J, Xu X, et al. A pair of chiral flavonolignans as novel anti-cyanobacterial allelochemicals derived from barley straw (Hordeum vulgare): characterization and comparison of their anti-cyanobacterial activities. Environ Microbiol. 2014;16:1238-51 pubmed publisher
    ..In this study, a pair of chiral flavonolignans were isolated from barley straw extract using a bioassay-guided isolation procedure against Microcystis sp...
  22. Wang Y, Li Y, Wang A, He X, Liao S, Lan Y. Two new phenolic glycosides from Inula cappa. J Asian Nat Prod Res. 2010;12:765-9 pubmed publisher
    ..The structures of the new compounds were elucidated by means of spectroscopic methods such as 1D, 2D NMR, and HR-ESI-MS. ..
  23. MacKinnon S, Hodder M, Craft C, Simmons Boyce J. Silyamandin, a new flavonolignan isolated from milk thistle tinctures. Planta Med. 2007;73:1214-6 pubmed
    ..Incubation of the tincture at 40 degrees C for 3 months resulted in an increase in the level of this compound, as observed in the LC/DAD silymarin profile. ..
  24. Ashtiani S, Hasanloo T, Bihamta M. Enhanced production of silymarin by Ag+ elicitor in cell suspension cultures of Silybum marianum. Pharm Biol. 2010;48:708-15 pubmed publisher
    Cell suspension cultures of Silybum marianum L. Gaertn (Compositae) produce silymarin, a mixture of flavonolignans. In an attempt to increase cell growth and silymarin production, we exposed cell cultures to various levels of Ag+ (0.2, 0...
  25. Tůmová L, Tůma J, Megusar K, Dolezal M. Substituted pyrazinecarboxamides as abiotic elicitors of flavolignan production in Silybum marianum (L.) gaertn cultures in vitro. Molecules. 2010;15:331-40 pubmed publisher
    Substituted pyrazinecarboxamides markedly influenced production of flavonolignans in Silybum marianum callus and suspension cultures...
  26. Sy Cordero A, Graf T, Nakanishi Y, Wani M, Agarwal R, Kroll D, et al. Large-scale isolation of flavonolignans from Silybum marianum extract affords new minor constituents and preliminary structure-activity relationships. Planta Med. 2010;76:644-7 pubmed publisher
  27. Jung Y, Kim D, Hwang J, Yun N, Lee Y, Han S, et al. Anti-inflammatory effect of tricin 4'-O-(threo-?-guaiacylglyceryl) ether, a novel flavonolignan compound isolated from Njavara on in RAW264.7 cells and in ear mice edema. Toxicol Appl Pharmacol. 2014;277:67-76 pubmed publisher
    ..Taken together, these results suggest that TTGE has anti-inflammatory properties through down-regulation of NF-?B and STAT3 pathways. ..
  28. Bijak M, Saluk Bijak J. Flavonolignans inhibit the arachidonic acid pathway in blood platelets. BMC Complement Altern Med. 2017;17:396 pubmed publisher
    ..Accordingly, the aim of our study was to determine the effects of three major flavonolignans (silybin, silychristin and silydianin) on COX pathway activity in blood platelets...
  29. Sharma D, Hall I. Hypolipidemic, anti-inflammatory, and antineoplastic activity and cytotoxicity of flavonolignans isolated from Hydnocarpus wightiana seeds. J Nat Prod. 1991;54:1298-302 pubmed
    b>Flavonolignans isolated from Hydnocarpus wightiana seeds, namely hydnowightin, hydnocarpin, and neohydnocarpin, demonstrated potent hypolipidemic activity in mice, lowering both serum cholesterol and triglyceride levels at 8 mg/kg/day ip...
  30. Zhu H, Brinda B, Chavin K, Bernstein H, Patrick K, Markowitz J. An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study. Drug Metab Dispos. 2013;41:1679-85 pubmed publisher
    ..Silybum marianum) extracts, one of the most widely used dietary supplements, contain a mixture of six major flavonolignans (silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin) and other components...
  31. Abouzid S, Ahmed H, Moawad A, Owis A, Chen S, Nachtergael A, et al. Chemotaxonomic and biosynthetic relationships between flavonolignans produced by Silybum marianum populations. Fitoterapia. 2017;119:175-184 pubmed publisher
    b>Flavonolignans constitute an important class of plant secondary metabolites formed by oxidative coupling of one flavonoid and one phenylpropanoid moiety...
  32. El Elimat T, Raja H, Graf T, Faeth S, Cech N, Oberlies N. Flavonolignans from Aspergillus iizukae, a fungal endophyte of milk thistle (Silybum marianum). J Nat Prod. 2014;77:193-9 pubmed publisher
    Silybin A (1), silybin B (2), and isosilybin A (3), three of the seven flavonolignans that constitute silymarin, an extract of the fruits of milk thistle (Silybum marianum), were detected for the first time from a fungal endophyte, ..
  33. Tůmová L, Tůma J, Dolezal M. Pyrazinecarboxamides as potential elicitors of flavonolignan and flavonoid production in Silybum marianum and Ononis arvensis cultures in vitro. Molecules. 2011;16:9142-52 pubmed publisher
    ..Both tested elicitors increased the production of flavonolignans in S. marianum callus and suspension cultures and flavonoids in O. arvensis callus and suspension cultures...
  34. Trailovic S, Ivanovic S, Varagić V. Ivermectin effects on motor coordination and contractions of isolated rat diaphragm. Res Vet Sci. 2011;91:426-33 pubmed publisher
    ..Effect on motor coordination is the first detectable clinical symptom of ivermectin toxicity and apparently is a result of its central effects. ..
  35. Pan M, Ho C. Chemopreventive effects of natural dietary compounds on cancer development. Chem Soc Rev. 2008;37:2558-74 pubmed publisher
  36. Wallace S, Carrier D, Clausen E. Batch solvent extraction of flavanolignans from milk thistle (Silybum marianum L. Gaertner). Phytochem Anal. 2005;16:7-16 pubmed
    ..8-, 0.95-, 1.7- and 1.6-fold higher than when extracting whole seeds. When extracting with boiling water, the yields of silychristin, silybinin A, and silybinin B were 380, 47 and 50% higher for whole seeds compared with defatted seeds. ..
  37. Tumova L, Gallová K, Rimáková J. [Silybum marianum in vitro]. Ceska Slov Farm. 2004;53:135-40 pubmed
    ..The maximal production of flavonolignans was achieved at the beginning of cultivation, i.e...
  38. Bueno Pérez L, Pan L, Sass E, Gupta S, Lehman A, Kinghorn A, et al. Potentiating effect of the flavonolignan (-)-hydnocarpin in combination with vincristine in a sensitive and P-gp-expressing acute lymphoblastic leukemia cell line. Phytother Res. 2013;27:1735-8 pubmed publisher
    ..0001), respectively, when compared to vincristine treatment as a single agent. To investigate the mechanism for the vincristine re-sensitization caused by (-)-hydnocarpin, the P-gp inhibitory effect of (-)-hydnocarpin was evaluated. ..
  39. Sy Cordero A, Day C, Oberlies N. Absolute configuration of isosilybin A by X-ray crystallography of the heavy atom analogue 7-(4-Bromobenzoyl)isosilybin A. J Nat Prod. 2012;75:1879-81 pubmed publisher
    Isosilybin A (1) is one of the major flavonolignans that constitute silymarin, an extract of the fruits (achenes) of milk thistle (Silybum marianum)...
  40. Wang J, Yin G, Zhou X, Su J, Li Y, Zhong H, et al. Anti-inflammatory flavonolignans from Hydnocarpus anthelminthica seeds. J Asian Nat Prod Res. 2011;13:80-3 pubmed publisher
    ..Bioassay showed that compounds 3-5 could inhibit nitric oxide production in LPS-stimulated RAW 264.7 macrophage cell lines, with IC(50) values of 7.81, 9.38, and 10.55 ?M, respectively...
  41. Hu M, Ning Y, Wu A, Xia Y, Zhu C, Lin C. [Study on chemical constituents of Callicarpa peii]. Zhong Yao Cai. 2013;36:563-6 pubmed
    ..To study the chemical constituents of Callicarpa peii...
  42. Khalili M, Hasanloo T, Kazemi Tabar S, Rahnama H. Influence of exogenous salicylic acid on flavonolignans and lipoxygenase activity in the hairy root cultures of Silybum marianum. Cell Biol Int. 2009;33:988-94 pubmed publisher
    ..marianum were investigated. Detection and identification of flavonolignans was carried out by high performance liquid chromatograph method...
  43. Pyszková M, Biler M, Biedermann D, Valentová K, Kuzma M, Vrba J, et al. Flavonolignan 2,3-dehydroderivatives: Preparation, antiradical and cytoprotective activity. Free Radic Biol Med. 2016;90:114-25 pubmed publisher
    ..Here, we explore the electron-donor properties of the major silymarin flavonolignans. Silybin (SB), silychristin (SCH), silydianin (SD) and their respective 2,3-dehydroderivatives (DHSB, DHSCH ..
  44. Guz N, Stermitz F. Synthesis and structures of regioisomeric hydnocarpin-type flavonolignans. J Nat Prod. 2000;63:1140-5 pubmed
    b>Flavonolignans represent natural compounds whose biosynthesis presumes a radical coupling of a ring B catecholic flavonoid with a molecule of coniferyl alcohol or an analogue...