Skip to main content

Advertisement

Log in

A pilot study of the UVA-photoprotective potential of dehydrosilybin, isosilybin, silychristin, and silydianin on human dermal fibroblasts

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

The exposure of naked unprotected skin to solar radiation may result in numerous acute and chronic undesirable effects. Evidence suggests that silymarin, a standardized extract from Silybum marianum (L.) Gaertn. seeds, and its major component silybin suppress UVB-induced skin damage. Here, we aimed to investigate the UVA-protective effects of silymarinʼs less abundant flavonolignans, specifically isosilybin (ISB), silychristin (SC), silydianin (SD), and 2,3-dehydrosilybin (DHSB). Normal human dermal fibroblasts (NHDF) pre-treated for 1 h with flavonolignans were then exposed to UVA light using a solar simulator. Their effects on reactive oxygen species (ROS), carbonylated proteins and glutathione (GSH) level, caspase-3 activity, single-strand breaks’ (SSBs) formation and protein level of matrix metalloproteinase-1 (MMP-1), heme oxygenase-1 (HO-1), and heat shock protein (HSP70) were evaluated. The most pronounced preventative potential was found for DHSB, a minor component of silymarin, and SC, the second most abundant flavonolignan in silymarin. They had significant effects on most of the studied parameters. Meanwhile, a photoprotective effect of SC was mostly found at double the concentration of DHSB. ISB and SD protected against GSH depletion, the generation of ROS, carbonylated proteins and SSBs, and caspase-3 activation, but had no significant effect on MMP-1, HO-1, or HSP70. In summary, DHSB and to a lesser extent other silymarin flavonolignans are potent UVA-protective compounds. However, due to the in vitro phototoxic potential of DHSB published elsewhere, further studies are needed to exclude phototoxicity for humans as well as to confirm our results on human skin ex vivo and in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Bosch R, Philips N, Suárez-Pérez JA, Juarranz A, Devmurari A, Chalensouk-Khaosaat J, González S (2015) Mechanisms of photoaging and cutaneous photocarcinogenesis, and photoprotective strategies with phytochemicals. Antioxidants (Basel) 4(2):248–268. https://doi.org/10.3390/antiox4020248

    Article  CAS  Google Scholar 

  2. Bosisio E, Benelli C, Pirola O (1992) Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacol Res 25(2):147–154

    Article  CAS  PubMed  Google Scholar 

  3. Caldecott KW (2001) Mammalian DNA single-strand break repair: an X-ra(y)ted affair. BioEssays 23(5):447–455

    Article  CAS  PubMed  Google Scholar 

  4. Collins AR (2009) Investigating oxidative DNA damage and its repair using the comet assay. Mutat Res 681(1):24–32

    Article  CAS  PubMed  Google Scholar 

  5. Fulop T, Khalil A, Larbi A (2012) The role of elastin peptides in modulating the immune response in aging and age-related diseases. Pathol Biol (Paris) 60(1):28–33. https://doi.org/10.1016/j.patbio.2011.10.006

    Article  CAS  Google Scholar 

  6. Gabrielová E, Křen V, Jabůrek M, Modrianský M (2015) Silymarin component 2,3-dehydrosilybin attenuates cardiomyocyte damage following hypoxia/reoxygenation by limiting oxidative stress. Physiol Res 64(1):79–91

    PubMed  Google Scholar 

  7. Gažák R, Svobodová A, Psotová J, Sedmera P, Přikrylová V, Walterová D, Křen V (2004) Oxidised derivatives of silybin and their antiradical and antioxidant activity. Bioorg Med Chem 12(21):5677–5687

    Article  CAS  PubMed  Google Scholar 

  8. Gažák R, Trouillas P, Biedermann D, Fuksová K, Marhol P, Kuzma M, Křen V (2013) Base-catalyzed oxidation of silybin and isosilybin into 2,3-dehydro derivatives. Tetrahedron Lett 54(4):315–317

    Article  CAS  Google Scholar 

  9. Křenek K, Marhol P, Peikerová Ž, Křen V, Biedermann D (2014) Preparatory separation of the silymarin flavonolignans by Sephadex LH-20 gel. Food Res Int 65:115–120

    Article  CAS  Google Scholar 

  10. Narayanapillai S, Agarwal C, Tilley C, Agarwal R (2012) Silibinin is a potent sensitizer of UVA radiation-induced oxidative stress and apoptosis in human keratinocyte HaCaT cells. Photochem Photobiol 88(5):1135–1140. https://doi.org/10.1111/j.1751-1097.2011.01050.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6(2):99–104

    Article  CAS  PubMed  Google Scholar 

  12. Psotová J, Chlopcíková S, Grambal F, Šimánek V, Ulrichová J (2002) Influence of silymarin and its flavonolignans on doxorubicin-iron induced lipid peroxidation in rat heart microsomes and mitochondria in comparison with quercetin. Phytother Res 16(S1):S63–S67

    Article  PubMed  Google Scholar 

  13. Pyszková M, Biler M, Biedermann D, Valentová K, Kuzma M, Vrba J, Ulrichová J, Sokolová R, Mojović M, Popović-Bijelić A, Kubala M, Trouillas P, Křen V, Vacek J (2016) Flavonolignan 2,3-dehydroderivatives: preparation, antiradical and cytoprotective activity. Free Radic Biol Med 90:114–125. https://doi.org/10.1016/j.freeradbiomed.2015.11.014

    Article  CAS  PubMed  Google Scholar 

  14. Radice M, Manfredini S, Ziosi P, Dissette V, Buso P, Fallacara A, Vertuani S (2016) Herbal extracts, lichens and biomolecules as natural photo-protection alternatives to synthetic UV filters. A systematic review. Fitoterapia 114:144–162. https://doi.org/10.1016/j.fitote.2016.09.003

    Article  CAS  PubMed  Google Scholar 

  15. Rajnochová Svobodová A, Gabrielová E, Michaelides L, Kosina P, Ryšavá A, Ulrichová J, Zálešák B, Vostálová J (2018) UVA-photoprotective potential of silymarin and silybin. Arch Dermatol Res 310(5):413–424. https://doi.org/10.1007/s00403-018-1828-6

    Article  CAS  PubMed  Google Scholar 

  16. Svobodová AR, Zálešák B, Biedermann D, Ulrichová J, Vostálová J (2016) Phototoxic potential of silymarin and its bioactive components. J Photochem Photobiol B 2016(156):61–68. https://doi.org/10.1016/j.jphotobiol.2016.01.011

    Article  CAS  Google Scholar 

  17. Rittié L, Fisher GJ (2002) UV-light-induced signal cascades and skin aging. Ageing Res Rev 14:705–720

    Article  Google Scholar 

  18. Simon MM, Reikerstorfer A, Schwarz A, Krone C, Luger TA, Jäättelä M, Schwarz T (1995) Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release. J Clin Invest 95(3):926–933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Singh RP, Agarwal R (2005) Mechanisms and preclinical efficacy of silibinin in preventing skin cancer. Eur J Cancer 41(13):1969–1979

    Article  CAS  Google Scholar 

  20. Svobodová A, Vostálová J (2010) Solar radiation induced skin damage: review of protective and preventive options. Int J Radiat Biol 86(12):999–1030. https://doi.org/10.3109/09553002.2010.501842

    Article  CAS  PubMed  Google Scholar 

  21. Svobodová A, Walterová D, Psotová J (2006) Influence of silymarin and its flavonolignans on H(2)O(2)-induced oxidative stress in human keratinocytes and mouse fibroblasts. Burns 32(8):973–979

    Article  PubMed  Google Scholar 

  22. Svobodová A, Zdařilová A, Walterová D, Vostálová J (2007) Flavonolignans from Silybum marianum moderate UVA-induced oxidative damage to HaCaT keratinocytes. J Dermatol Sci 48(3):213–224

    Article  CAS  PubMed  Google Scholar 

  23. Tomaino A, Cristani M, Cimino F, Speciale A, Trombetta D, Bonina F, Saija A (2006) In vitro protective effect of a Jacquez grapes wine extract on UVB-induced skin damage. Toxicol In Vitro 20(8):1395–1402

    Article  CAS  PubMed  Google Scholar 

  24. Trouillas P, Marsal P, Svobodová A, Vostálová J, Gazák R, Hrbác J, Sedmera P, Kren V, Lazzaroni R, Duroux JL, Walterová D (2008) Mechanism of the antioxidant action of silybin and 2,3-dehydrosilybin flavonolignans: a joint experimental and theoretical study. J Phys Chem A 112(5):1054–1063. https://doi.org/10.1021/jp075814h (Epub 15 Jan 2008)

    Article  CAS  PubMed  Google Scholar 

  25. Vaid M, Katiyar SK (2010) Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.) (Review). Int J Oncol 36(5):1053–1060

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Vostálová J, Tinková E, Biedermann D, Kosina P, Ulrichová J, Rajnochová Svobodová A (2019) Skin protective activity of silymarin and its flavonolignans. Molecules 24(6):1022. https://doi.org/10.3390/molecules24061022

    Article  CAS  PubMed Central  Google Scholar 

  27. Xiang Y, Liu G, Yang L, Zhong JL (2011) UVA-induced protection of skin through the induction of heme oxygenase-1. Biosci Trends 5(6):239–244

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the Grant GACR 15-10897S, IGA_LF_2019_015, IGA_LF_2018_012, and the Institutional Support of Palacký University in Olomouc-RVO 61989592. We wish to thank Iveta Hatalová (University Hospital in Olomouc) for assistance with skin tissue donor recruitment.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jitka Vostálová.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rajnochová Svobodová, A., Gabrielová, E., Ulrichová, J. et al. A pilot study of the UVA-photoprotective potential of dehydrosilybin, isosilybin, silychristin, and silydianin on human dermal fibroblasts. Arch Dermatol Res 311, 477–490 (2019). https://doi.org/10.1007/s00403-019-01928-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-019-01928-7

Keywords

Navigation