Silybum marianum (L.) is a medicinal plant traditionally used in treatment of liver disorders. In last decades, silymarin (SM), a standardized extract from S. marianum seeds has been studied for its dermatological application, namely for UVB-protective properties. However, information on SM and its polyphenols effect on activity of enzymes participating in the (photo)aging process is limited. Therefore, evaluation of SM and its flavonolignans potential to inhibit collagenase, elastase, and hyaluronidase in tube tests was the goal of this study. The antioxidant and UV screening properties of SM and its flavonolignans silybin, isosilybin, silydianin, silychristin and 2,3-dehydrosilybin (DHSB) were also evaluated by a DPPH assay and spectrophotometrical measurement. DHSB showed the highest ability to scavenge DPPH radical and also revealed the highest UVA protection factor (PF-UVA) that corresponds with its absorption spectrum. SM and studied flavonolignans were found to exhibit anti-collagenase and anti-elastase activity. The most potent flavonolignan was DHSB. None of studied flavonolignans or SM showed anti-hyaluronidase activity. Our results suggest that SM and its flavonolignans may be useful agents for skin protection against the harmful effects of full-spectrum solar radiation including slowing down skin (photo)aging.

Department of Medical Chemistry and Biochemistry Faculty of Medicine and Dentistry Palacký University Hněvotínská 3 775 15 Olomouc Czech Republic

Laboratory of Biotransformation Institute of Microbiology Academy of Sciences of the Czech Republic Vídeňská 1083 142 20 Prague Czech Republic

See more in PubMed

Rinnerthaler M., Bischof J., Streubel M.K., Trost A., Richter K. Oxidative stress in aging human skin. Biomolecules. 2015;5:545–589. doi: 10.3390/biom5020545. PubMed DOI PMC

Rijken F., Bruijnzeel P.L. The pathogenesis of photoaging: The role of neutrophils and neutrophil-derived enzymes. J. Investig. Dermatol. Symp. Proc. 2009;14:67–72. doi: 10.1038/jidsymp.2009.15. PubMed DOI

Buhren B.A., Schrumpf H., Hoff N.P., Bölke E., Hilton S., Gerber P.A. Hyaluronidase: From clinical applications to molecular and cellular mechanisms. Eur. J. Med. Res. 2016;21:5. doi: 10.1186/s40001-016-0201-5. PubMed DOI PMC

Tundis R., Loizzo M.R., Bonesi M., Menichini F. Potential role of natural compounds against skin aging. Curr Med Chem. 2015;22:1515–1538. doi: 10.2174/0929867322666150227151809. 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

Vaid M., Katiyar S.K. Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.) (Review) Int. J. Oncol. 2010;36:1053–1060. doi: 10.3892/ijo_00000586. PubMed DOI PMC

Surai P.F. Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives. Antioxidants. 2015;4:204–247. doi: 10.3390/antiox4010204. PubMed DOI PMC

Gažák R., Svobodová A., Psotová J., Sedmera P., Přikrylová V., Walterová D., Kren 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

Rajnochová Svobodová A., Gabrielová E., Michaelides L., Kosina P., Ryšavá A., Ulrichová J., Zálešák B., Vostálová J. UVA-photoprotective potential of silymarin and silybin. Arch. Dermatol. Res. 2018;310:413–424. doi: 10.1007/s00403-018-1828-6. PubMed DOI

Katiar S.K. Silymarin and skin cancer prevention: Anti-inflammatory, antioxidant and immunomodulatory effects (Review) Int. J. Oncol. 2005;26:169–176. doi: 10.3892/ijo.26.1.169. PubMed DOI

Pittayapruek P., Meephansan J., Prapapan O., Komine M., Ohtsuki M. Role of matrix metalloproteinases in photoaging and photocarcinogenesis. Int. J. Mol. Sci. 2016;17:868. doi: 10.3390/ijms17060868. PubMed DOI PMC

Anthony K.P., Saleh M.A. Free radical scavenging and antioxidant activities of silymarin components. Antioxidants. 2013;2:398–407. doi: 10.3390/antiox2040398. PubMed DOI PMC

Köksal E., Gülçin I., Beyza S., Sarikaya O., Bursal E. In vitro antioxidant activity of silymarin. J. Enzyme Inhib. Med. Chem. 2009;24:395–405. doi: 10.1080/14756360802188081. PubMed DOI

Abenavoli L., Capasso R., Milic N., Capasso F. Milk thistle in liver diseases: Past, present, future. Phytother. Res. 2010;24:1423–1432. doi: 10.1002/ptr.3207. PubMed DOI

Svobodová A., Zdařilová A., Malisková J., Mikulková H., Walterová D., Vostalová J. Attenuation of UVA-induced damage to human keratinocytes by silymarin. J. Dermatol. Sci. 2007;46:21–30. doi: 10.1016/j.jdermsci.2006.12.009. PubMed DOI

Svobodová A., Zdařilová A., Walterová D., Vostálová J. Flavonolignans from Silybum marianum moderate UVA-induced oxidative damage to HaCaT keratinocytes. J. Dermatol. Sci. 2007;48:213–224. doi: 10.1016/j.jdermsci.2007.06.008. PubMed DOI

Pientaweeratch S., Panapisal V., Tansirikongkol A. Antioxidant, anti-collagenase and anti-elastase activities of Phyllanthus emblica, Manilkara zapota and silymarin: An in vitro comparative study for anti-aging applications. Pharm. Biol. 2016;54:1865–1872. doi: 10.3109/13880209.2015.1133658. PubMed DOI

Vimalraj S., Rajalakshmi S., Saravanan S., Raj Preeth D., LA Vasanthi R., Shairam M., Chatterjee S. Synthesis and characterization of zinc-silibinin complexes: A potential bioactive compound with angiogenic, and antibacterial activity for bone tissue engineering. Colloids Surf. B Biointerfaces. 2018;167:134–143. doi: 10.1016/j.colsurfb.2018.04.007. PubMed DOI

Lee D.H., Oh J.H., Chung J.H. Glycosaminoglycan and proteoglycan in skin aging. J. Dermatol. Sci. 2016;83:174–181. doi: 10.1016/j.jdermsci.2016.05.016. PubMed DOI

Svobodová A., Vostálová J. Solar radiation induced skin damage: Review of protective and preventive options. Int. J. Radiat. Biol. 2010;86:999–1030. doi: 10.3109/09553002.2010.501842. PubMed DOI

Couteau C., Cheignon C., Paparis E., Coiffard L.J. Silymarin, a molecule of interest for topical photoprotection. Nat. Prod. Res. 2012;26:2211–2214. doi: 10.1080/14786419.2011.637219. PubMed DOI

Rajnochová Svobodová A., Zálešák B., Biedermann D., Ulrichová J., Vostálová J. Phototoxic potential of silymarin and its bioactive components. J. Photochem. Photobiol. B. 2016;156:61–68. doi: 10.1016/j.jphotobiol.2016.01.011. PubMed 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

Gažák R., Trouillas P., Biedermann D., Fuksová K., Marhol P., Kuzma M., Kren V. Base-catalyzed oxidation of silybin and isosilybin into 2,3-dehydro derivatives. Tetrahedron Lett. 2013;54:315–317. doi: 10.1016/j.tetlet.2012.11.049. 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. Molecule. 2019;24:61. doi: 10.3390/molecules24010061. PubMed DOI PMC

Sayre R.M., Agin P.P., Levee G.I., Marlowe E. Comparison of in vivo and in vitro testing of sunscreening formulas. Photochem. Photobiol. 1979;29:559–566. doi: 10.1111/j.1751-1097.1979.tb07090.x. PubMed DOI

Diffey B.L., Robson J. A new substrate to measure sunscreen protection factors throughout the ultraviolet spectrum. J. Soc. Cosmet. Chem. 1989;40:127–133.

Couteau C., Couteau O., Alami-El Boury S., Coiffard L.J. Sunscreen products: What do they protect us from? Int. J. Pharm. 2011;415:181–184. doi: 10.1016/j.ijpharm.2011.05.071. PubMed DOI

Karsili T.N., Marchetti B., Ashfold M.N., Domcke W. Ab initio study of potential ultrafast internal conversion routes in oxybenzone, caffeic acid, and ferulic acid: Implications for sunscreens. J. Phys. Chem. A. 2014;118:11999–12010. doi: 10.1021/jp507282d. PubMed DOI

Ndlovu G., Fouche G., Tselanyane M., Cordier W., Steenkamp V. In vitro determination of the anti-aging potential of four southern African medicinal plants. BMC Complement Altern. Med. 2013;13:304. doi: 10.1186/1472-6882-13-304. PubMed DOI PMC

Maity N., Nema N.K., Sarkar B.K., Mukherjee P.K. Standardized Clitoria ternatea leaf extract as hyaluronidase, elastase and matrix-metalloproteinase-1 inhibitor. Indian J. Pharmacol. 2012;44:584–587. doi: 10.4103/0253-7613.100381. PubMed DOI PMC

Hesperidin, Hesperetin, Rutinose, and Rhamnose Act as Skin Anti-Aging Agents

Dehydroflavonolignans from Silymarin Potentiate Transition Metal Toxicity In Vitro but Are Protective for Isolated Erythrocytes Ex Vivo

Presence of Mycotoxins in Milk Thistle (Silybum marianum) Food Supplements: A Review

Simple and Rapid HPLC Separation and Quantification of Flavonoid, Flavonolignans, and 2,3-Dehydroflavonolignans in Silymarin

Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives