Simple and Rapid HPLC Separation and Quantification of Flavonoid, Flavonolignans, and 2,3-Dehydroflavonolignans in Silymarin
Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články
Grantová podpora
18-00132S
Grantová Agentura České Republiky
LTC18003, and LTC19039
Ministerstvo Školství, Mládeže a Tělovýchovy
CA16112 NutRedOx and CA16205 UNGAP
European Cooperation in Science and Technology
PubMed
31973217
PubMed Central
PMC7073671
DOI
10.3390/foods9020116
PII: foods9020116
Knihovny.cz E-zdroje
- Klíčová slova
- HPLC-MS separation, diastereoisomers, enantiomers, flavonolignans, milk thistle, quantification, silymarin,
- Publikační typ
- časopisecké články MeSH
Herbal preparations from Silybum marianum have been used since the fourth century BC in liver disease treatment and against numerous other pathologies. Consumption of silymarin containing drugs and food supplements continues to increase. Precise, fast, reliable, and complex determination of all components of silymarin preparations is paramount for assessing its pharmacological quality. We present here simple and fast HPLC-DAD and LC-MS analytical methods for the determination and quantification of all known silymarin components, including 2,3-dehydroflavonolignans that has not been achieved so far. The first method, using a common C18 column, allows baseline separation of previously inseparable silychristin A, B, isosilychristin, and silydianin. Moreover, this method allowed detection of three so far unknown silymarin components. In addition, the first analytical separation of enantiomers of 2,3-dehydrosilybin was achieved using a Lux 3μ Cellulose-4 chiral column, providing even more accurate description of silymarin composition. 2,3-Dehydroflavonolignans were isolated for the first time from silymarin using preparative chromatography on C18 and ASAHIPAK columns, and 2,3-dehydrosilychristin and 2,3-dehydrosilybin were for the first time conclusively confirmed by HPLC, MS, and NMR to be silymarin components. Using the optimized analytical methods, six various silymarin preparations were analyzed showing substantial differences in the composition.
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Martin R.J., Lauren D.R., Smith W.A., Jensen D.J., Deo B., Douglas J.A. Factors influencing silymarin content and composition in variegated thistle (Silybum marianum) N. Z. J. Crop Hortic. Sci. 2006;34:239–245. doi: 10.1080/01140671.2006.9514413. DOI
Graf T.N., Cech N.B., Polyak S.J., Oberlies N.H. 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. doi: 10.1016/j.jpba.2016.04.028. PubMed DOI PMC
Kuki Á., Nagy L., Deák G., Nagy M., Zsuga M., Kéki S. Identification of silymarin constituents: An improved HPLC–MS method. Chromatographia. 2012;75:175–180. doi: 10.1007/s10337-011-2163-7. DOI
Wallace S., Carrier D.J., Beitle R.R., Clausen E.C., Griffis C.L. HPLC-UV and LC-MS-MS characterization of silymarin in milk thistle seeds and corresponding products. J. Nutraceutic. Funct. Med. Food. 2003;4:37–48. doi: 10.1300/J133v04n02_05. DOI
Althagafy H.S., Meza-Aviña M.E., Oberlies N.H., Croatt M.P. Mechanistic study of the biomimetic synthesis of flavonolignan diastereoisomers in milk thistle. J. Org. Chem. 2013;78:7594–7600. doi: 10.1021/jo4011377. PubMed DOI PMC
Gažák R., Svobodová A., Psotová J., Sedmera P., Přikrylová V., Walterová D., Křen V. Oxidised derivatives of silybin and their antiradical and antioxidant activity. Bioorg. Med. Chem. 2004;12:5677–5687. doi: 10.1016/j.bmc.2004.07.064. PubMed DOI
Chambers C.S., Holečková V., Petrásková L., Biedermann D., Valentová K., Buchta M., Křen V. The silymarin composition… and why does it matter? Food Res. Int. 2017;100:339–353. doi: 10.1016/j.foodres.2017.07.017. PubMed DOI
Biedermann D., Vavříková E., Cvak L., Křen V. Chemistry of silybin. Nat. Prod. Rep. 2014;31:1138–1157. doi: 10.1039/C3NP70122K. PubMed DOI
Plíšková M., Vondráček J., Křen V., Gažák R., Sedmera P., Walterová D., Psotová J., Šimánek V., Machala M. Effects of silymarin flavonolignans and synthetic silybin derivatives on estrogen and aryl hydrocarbon receptor activation. Toxicology. 2005;215:80–89. doi: 10.1016/j.tox.2005.06.020. PubMed DOI
Davis-Searles P.R., Nakanishi Y., Kim N.-C., Graf T.N., Oberlies N.H., Wani M.C., Wall M.E., Agarwal R., Kroll D.J. 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;65:4448–4457. doi: 10.1158/0008-5472.CAN-04-4662. PubMed DOI
Biedermann D., Buchta M., Holečková V., Sedlák D., Valentová K., Cvačka J., Bednárová L., Křenková A., Kuzma M., Škuta C., et al. Silychristin: Skeletal alterations and biological activities. J. Nat. Prod. 2016;79:3086–3092. doi: 10.1021/acs.jnatprod.6b00750. PubMed DOI
Marhol P., Bednář P., Kolářová P., Večeřa R., Ulrichová J., Tesařová E., Vavříková E., Kuzma M., Křen V. Pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasma. J. Funct. Food. 2015;14:570–580. doi: 10.1016/j.jff.2015.02.031. DOI
Filippopoulou K., Papaevgeniou N., Lefaki M., Paraskevopoulou A., Biedermann D., Křen V., Chondrogianni N. 2,3-Dehydrosilybin A/B as a pro-longevity and anti-aggregation compound. Free Radic. Biol. Med. 2017;103:256–267. doi: 10.1016/j.freeradbiomed.2016.12.042. PubMed DOI
Rajnochová Svobodová A., Gabrielová E., Ulrichová J., Zálešák B., Biedermann D., Vostálová J. A pilot study of the UVA-photoprotective potential of dehydrosilybin, isosilybin, silychristin, and silydianin on human dermal fibroblasts. Arch. Dermatol. Res. 2019;311:477–490. doi: 10.1007/s00403-019-01928-7. PubMed DOI
Kosina P., Paloncýová M., Rajnochová Svobodová A., Zálešák B., Biedermann D., Ulrichová J., Vostálová J. Dermal delivery of selected polyphenols from Silybum marianum. Theoretical and experimental study. Molecules. 2018;24:61. doi: 10.3390/molecules24010061. PubMed DOI PMC
Vostálová J., Tinková E., Biedermann D., Kosina P., Ulrichová J., Rajnochová Svobodová A. Skin protective activity of silymarin and its flavonolignans. Molecules. 2019;24:1022. doi: 10.3390/molecules24061022. PubMed DOI PMC
Tilley C., Deep G., Agarwal C., Wempe M.F., Biedermann D., Valentová K., Kren V., Agarwal R. 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. doi: 10.1002/mc.22253. PubMed DOI PMC
Fenclová M., Nováková A., Viktorová J., Jonatová P., Džuman Z., Ruml T., Křen V., Hajšlová J., Vítek L., Stránská-Zachariášová M. 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. 2019;9:11118. doi: 10.1038/s41598-019-47250-0. PubMed DOI PMC
Csupor D., Csorba A., Hohmann J. Recent advances in the analysis of flavonolignans of Silybum marianum. J. Pharm. Biomed. Anal. 2016;130:301–317. doi: 10.1016/j.jpba.2016.05.034. PubMed DOI
Karkanis A., Bilalis D., Efthimiadou A. Cultivation of milk thistle (Silybum marianum L. Gaertn.), a medicinal weed. Ind. Crop. Prod. 2011;34:825–830. doi: 10.1016/j.indcrop.2011.03.027. DOI
Džubák P., Hajdúch M., Gažák R., Svobodová A., Psotová J., Walterová D., Sedmera P., Křen V. New derivatives of silybin and 2,3-dehydrosilybin and their cytotoxic and P-glycoprotein modulatory activity. Bioorg. Med. Chem. 2006;14:3793–3810. doi: 10.1016/j.bmc.2006.01.035. PubMed DOI
Biedermann D., Moravcová V., Valentová K., Kuzma M., Petrásková L., Císařová I., Křen V. Oxidation of flavonolignan silydianin to unexpected lactone-acid derivative. Phytochem. Lett. 2019;30:14–20. doi: 10.1016/j.phytol.2019.01.006. DOI
Křenek K., Marhol P., Peikerová Ž., Křen V., Biedermann D. Preparatory separation of the silymarin flavonolignans by Sephadex LH-20 gel. Food Res. Int. 2014;65:115–120. doi: 10.1016/j.foodres.2014.02.001. DOI
Pyszková M., Biler M., Biedermann D., Valentová K., Kuzma M., Vrba J., Ulrichová J., Sokolová R., Mojovic M., Popovic-Bijelic A., et al. Flavonolignan 2,3-dehydroderivatives: Preparation, antiradical and cytoprotective activity. Free Radic. Biol. Med. 2016;90:114–125. doi: 10.1016/j.freeradbiomed.2015.11.014. PubMed DOI
Novotná M., Gažák R., Biedermann D., Di Meo F., Marhol P., Kuzma M., Bednárová L., Fuksová K., Trouillas P., Křen V. cis–trans Isomerization of silybins A and B. Beilstein J. Org. Chem. 2014;10:1047–1063. doi: 10.3762/bjoc.10.105. PubMed DOI PMC
Liu H., Du Z., Yuan Q. A novel rapid method for simultaneous determination of eight active compounds in silymarin using a reversed-phase UPLC-UV detector. J. Chromatogr. B. 2009;877:4159–4163. doi: 10.1016/j.jchromb.2009.11.001. PubMed DOI
AbouZid S.F., Chen S.N., Pauli G.F. Silymarin content in Silybum marianum populations growing in Egypt. Ind. Crop. Prod. 2016;83:729–737. doi: 10.1016/j.indcrop.2015.12.012. PubMed DOI PMC
Kim N.C., Graf T.N., Sparacino C.M., Wani M.C., Wall M.E. Complete isolation and characterization of silybins and isosilybins from milk thistle (Silybum marianum) Org. Biomol. Chem. 2003;1:1684–1689. doi: 10.1039/b300099k. PubMed DOI
Cai X., Li D., Qiao J., Lian H., Wang S. Determination of silymarin flavonoids by HPLC and LC-MS and investigation of extraction rate of silymarin in Silybum marianum fruits by boiling water. Asian J. Chem. 2009;21:63–74.
Keshavarz Afshar R., Chaichi M.R., Ansari Jovini M., Jahanzad E., Hashemi M. Accumulation of silymarin in milk thistle seeds under drought stress. Planta. 2015;242:539–543. doi: 10.1007/s00425-015-2265-9. PubMed DOI
Poppe L., Petersen M. Variation in the flavonolignan composition of fruits from different Silybum marianum chemotypes and suspension cultures derived therefrom. Phytochemistry. 2016;131:68–75. doi: 10.1016/j.phytochem.2016.09.003. PubMed DOI
Bilia A.R., Salvini D., Mazzi G., Vincieri F.F. Characterization of calendula flower, milk-thistle fruit, and passion flower tinctures by HPLC-DAD and HPLC-MS. Chromatographia. 2000;53:210–215. doi: 10.1007/BF02491573. DOI
Gažák R., Sedmera P., Marzorati M., Riva S., Křen V. Laccase-mediated dimerization of the flavonolignan silybin. J. Mol. Catal. B Enzym. 2008;50:87–92. doi: 10.1016/j.molcatb.2007.09.005. DOI
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