Skip to main content
SpringerLink
Log in

Probing the effects of sweet cherry (Prunus avium L.) extract on 2D and 3D human skin models

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Natural products are not only positioned in the heart of traditional medicine but also in modern medicine as many current drugs are coming from natural sources. Apart from the field of medicine and therapeutics, natural products are broadly used in other industrial fields such as nutrition, skincare products and nanotechnology.

Methods and results

The aim of this study was to assess the effects of sweet cherry (Prunus avium L.) fruit extract from the Greek native cultivar ‘Vasiliadi’, on the human 2D and 3D in vitro models in order to investigate its potential impact on skin. We focused on 2D culture of primary normal human epidermal keratinocytes (NHEK) that were treated with sweet cherry fruit extract. In the first place, we targeted fruit extract potential cytotoxicity by determining ATP intracellular levels. Furthermore, we assessed its potential skin irritability by using 3D skin model. To better understand the bioactivity of sweet cherry fruit. extract, we used qPCR to study the expression of various genes that are implicated in the skin functions. Our experiments showed that sweet cherry fruit extract is non-toxic in 2D keratinocytes culture as well as non-irritant in 3D skin model. Our results revealed that the extract mediated important pathways for the optimum epidermis function such as cell proliferation, immune and inflammatory response.

Conclusion

The sweet cherry fruit extracts possesses significant activity in epidermis function without any potential of cytotoxicity or skin irritability, which makes it a rather promising active agent for skincare.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Availability of data and material

Not applicable.

Code availability

Not applicable.

References

  1. Dyring-Andersen B, Løvendorf MB, Coscia F et al (2020) Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin. Nat Commun 11:5587. https://doi.org/10.1038/s41467-020-19383-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Johansen C (2017) Generation and culturing of primary human keratinocytes from adult skin. J Vis Exp. https://doi.org/10.3791/56863

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gruber F, Kremslehner C, Eckhart L, Tschachler E (2020) Cell aging and cellular senescence in skin aging—recent advances in fibroblast and keratinocyte biology. Exp Gerontol 130:110780. https://doi.org/10.1016/j.exger.2019.110780

    Article  CAS  PubMed  Google Scholar 

  4. Byrd AL, Belkaid Y, Segre JA (2018) The human skin microbiome. Nat Rev Microbiol 16:143–155. https://doi.org/10.1038/nrmicro.2017.157

    Article  CAS  PubMed  Google Scholar 

  5. Nestle FO, Di Meglio P, Qin J-Z, Nickoloff BJ (2009) Skin immune sentinels in health and disease. Nat Rev Immunol 9:679–691. https://doi.org/10.1038/nri2622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fowler JF, Woolery-Lloyd H, Waldorf H, Saini R (2010) Innovations in natural ingredients and their use in skin care. J Drugs Dermatol 9:S72–S81 (quiz s82-3)

    PubMed  Google Scholar 

  7. Liu RH (2003) Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr 78:517S-520S. https://doi.org/10.1093/ajcn/78.3.517S

    Article  CAS  PubMed  Google Scholar 

  8. Mintie CA, Singh CK, Ahmad N (2020) Whole fruit phytochemicals combating skin damage and carcinogenesis. Transl Oncol 13:146–156. https://doi.org/10.1016/j.tranon.2019.10.014

    Article  PubMed  Google Scholar 

  9. Commisso M, Bianconi M, Di Carlo F et al (2017) Multi-approach metabolomics analysis and artificial simplified phytocomplexes reveal cultivar-dependent synergy between polyphenols and ascorbic acid in fruits of the sweet cherry (Prunus avium L.). PLoS ONE 12:e0180889. https://doi.org/10.1371/journal.pone.0180889

    Article  PubMed  PubMed Central  Google Scholar 

  10. McCune LM, Kubota C, Stendell-Hollis NR, Thomson CA (2010) Cherries and health: a review. Crit Rev Food Sci Nutr 51:1–12. https://doi.org/10.1080/10408390903001719

    Article  CAS  Google Scholar 

  11. Bastos C, Barros L, Dueñas M et al (2015) Chemical characterisation and bioactive properties of Prunus avium L.: the widely studied fruits and the unexplored stems. Food Chem 173:1045–1053. https://doi.org/10.1016/j.foodchem.2014.10.145

    Article  CAS  PubMed  Google Scholar 

  12. Kelley D, Adkins Y, Laugero K (2018) A review of the health benefits of cherries. Nutrients 10:368. https://doi.org/10.3390/nu10030368

    Article  CAS  PubMed Central  Google Scholar 

  13. Garrido M, Espino J, Toribio-Delgado AF et al (2012) A jerte valley cherry-based product as a supply of tryptophan. Int J Tryptophan Res 5:IJTR.S9394. https://doi.org/10.4137/IJTR.S9394

    Article  CAS  Google Scholar 

  14. Agulló-Chazarra L, Borrás-Linares I, Lozano-Sánchez J et al (2020) Sweet cherry byproducts processed by green extraction techniques as a source of bioactive compounds with antiaging properties. Antioxidants 9:418. https://doi.org/10.3390/antiox9050418

    Article  CAS  PubMed Central  Google Scholar 

  15. Michailidis M, Karagiannis E, Tanou G et al (2020) Sweet cherry fruit cracking: follow-up testing methods and cultivar-metabolic screening. Plant Methods 16:51. https://doi.org/10.1186/s13007-020-00593-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Karagiannis E, Sarrou E, Michailidis M et al (2020) Fruit quality trait discovery and metabolic profiling in sweet cherry genebank collection in Greece. Food Chem. https://doi.org/10.1016/j.foodchem.2020.128315

    Article  PubMed  Google Scholar 

  17. Letsiou S, Karamaouna A, Ganopoulos I et al (2021) The pleiotropic effects of Prunus avium L. extract against oxidative stress on human fibroblasts. An in vitro approach. Mol Biol Rep 48:4441–4448. https://doi.org/10.1007/s11033-021-06464-0

    Article  CAS  PubMed  Google Scholar 

  18. Letsiou S, Bakea A, Le Goff G et al (2020) In vitro protective effects of marine-derived Aspergillus puulaauensis TM124-S4 extract on H2O2-stressed primary human fibroblasts. Toxicol Vitr 66:104869. https://doi.org/10.1016/j.tiv.2020.104869

    Article  CAS  Google Scholar 

  19. Letsiou S, Kapazoglou A, Tsaftaris A (2020) Transcriptional and epigenetic effects of Vitis vinifera L. leaf extract on UV-stressed human dermal fibroblasts. Mol Biol Rep 47:5763–5772. https://doi.org/10.1007/s11033-020-05645-7

    Article  CAS  PubMed  Google Scholar 

  20. Letsiou S, Kalliampakou K, Gardikis K et al (2017) Skin protective effects of Nannochloropsis gaditana extract on H2O2-stressed human dermal fibroblasts. Front Mar Sci. https://doi.org/10.3389/fmars.2017.00221

    Article  Google Scholar 

  21. Letsiou S, Bakea A, Holefors A, Rembiesa J (2020) In vitro protective effects of Paeonia mascula subsp. hellenica callus extract on human keratinocytes. Sci Rep 10:19213. https://doi.org/10.1038/s41598-020-76169-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Oyetayo A, Bada S (2017) Phytochemical screening and antibacterial activity of Prunus avium extracts against selected human pathogens. J Complement Altern Med Res 4:1–8. https://doi.org/10.9734/JOCAMR/2017/37272

    Article  Google Scholar 

  23. Ballistreri G, Continella A, Gentile A et al (2013) Fruit quality and bioactive compounds relevant to human health of sweet cherry (Prunus avium L.) cultivars grown in Italy. Food Chem 140:630–638. https://doi.org/10.1016/j.foodchem.2012.11.024

    Article  CAS  PubMed  Google Scholar 

  24. Basanta MF, de Escalada Plá MF, Raffo MD et al (2014) Cherry fibers isolated from harvest residues as valuable dietary fiber and functional food ingredients. J Food Eng 126:149–155. https://doi.org/10.1016/j.jfoodeng.2013.11.010

    Article  CAS  Google Scholar 

  25. Di Cagno R, Surico RF, Minervini G et al (2011) Exploitation of sweet cherry (Prunus avium L.) puree added of stem infusion through fermentation by selected autochthonous lactic acid bacteria. Food Microbiol 28:900–909. https://doi.org/10.1016/j.fm.2010.12.008

    Article  CAS  PubMed  Google Scholar 

  26. Letsiou S, Bakea A, Le GG et al (2020) Marine fungus Aspergillus chevalieri TM2-S6 extract protects skin fibroblasts from oxidative stress. Mar Drugs 18:460. https://doi.org/10.3390/md18090460

    Article  CAS  PubMed Central  Google Scholar 

  27. Ahmed IA, Mikail MA, Zamakshshari N, Abdullah A-SH (2020) Natural anti-aging skincare: role and potential. Biogerontology 21:293–310. https://doi.org/10.1007/s10522-020-09865-z

    Article  PubMed  Google Scholar 

  28. Agathokleous E, Calabrese EJ (2019) Hormesis: the dose response for the 21st century: the future has arrived. Toxicology 425:152249. https://doi.org/10.1016/j.tox.2019.152249

    Article  CAS  PubMed  Google Scholar 

  29. Sulyok S, Wankell M, Alzheimer C, Werner S (2004) Activin: an important regulator of wound repair, fibrosis, and neuroprotection. Mol Cell Endocrinol 225:127–132. https://doi.org/10.1016/j.mce.2004.07.011

    Article  CAS  PubMed  Google Scholar 

  30. Eisinger M, Sadan S, Silver IA, Flick RB (1988) Growth regulation of skin cells by epidermal cell-derived factors: implications for wound healing. Proc Natl Acad Sci USA 85:1937–1941. https://doi.org/10.1073/pnas.85.6.1937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mantovani A, Sica A, Sozzani S et al (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677–686. https://doi.org/10.1016/j.it.2004.09.015

    Article  CAS  PubMed  Google Scholar 

  32. Koch A, Polverini P, Kunkel S et al (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258:1798–1801. https://doi.org/10.1126/science.1281554

    Article  CAS  PubMed  Google Scholar 

  33. Azimi B, Thomas L, Fusco A et al (2020) Electrosprayed Chitin Nanofibril/Electrospun Polyhydroxyalkanoate Fiber Mesh as Functional Nonwoven for Skin Application. J Funct Biomater 11:62. https://doi.org/10.3390/jfb11030062

    Article  CAS  PubMed Central  Google Scholar 

  34. Fusco A, Savio V, Cammarota M et al (2017) Beta-Defensin-2 and Beta-Defensin-3 reduce intestinal damage caused by Salmonella typhimurium modulating the expression of cytokines and enhancing the probiotic activity of Enterococcus faecium. J Immunol Res 2017:1–9. https://doi.org/10.1155/2017/6976935

    Article  CAS  Google Scholar 

  35. Adorno-Cruz V, Liu H (2019) Regulation and functions of integrin α2 in cell adhesion and disease. Genes Dis 6:16–24. https://doi.org/10.1016/j.gendis.2018.12.003

    Article  CAS  PubMed  Google Scholar 

  36. Pummi K, Malminen M, Aho H et al (2001) Epidermal tight junctions: ZO-1 and occludin are expressed in mature, developing, and affected skin and in vitro differentiating keratinocytes. J Invest Dermatol 117:1050–1058. https://doi.org/10.1046/j.0022-202x.2001.01493.x

    Article  CAS  PubMed  Google Scholar 

  37. Miyagawa M, Fujikawa A, Nagadome M et al (2019) Glycosylceramides Purified from the Japanese Traditional Non-Pathogenic Fungus Aspergillus and Koji Increase the Expression of Genes Involved in Tight Junctions and Ceramide Delivery in Normal Human Epidermal Keratinocytes. Fermentation 5:43. https://doi.org/10.3390/fermentation5020043

    Article  CAS  Google Scholar 

  38. Jia Z, Wang X, Wang X et al (2018) Calycosin alleviates allergic contact dermatitis by repairing epithelial tight junctions via down-regulating HIF-1α. J Cell Mol Med 22:4507–4521. https://doi.org/10.1111/jcmm.13763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Chen D, Wang Z, Ren C et al (2013) Abnormal expression of paxillin correlates with tumor progression and poor survival in patients with gastric cancer. J Transl Med 11:277. https://doi.org/10.1186/1479-5876-11-277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sando GN, Zhu H, Weis JM et al (2003) Caveolin expression and localization in human keratinocytes suggest a role in lamellar granule biogenesis. j Invest Dermatol 120:531–541. https://doi.org/10.1046/j.1523-1747.2003.12051.x

    Article  CAS  PubMed  Google Scholar 

  41. Blouin CM, Le Lay S, Eberl A et al (2010) Lipid droplet analysis in caveolin-deficient adipocytes: alterations in surface phospholipid composition and maturation defects. J Lipid Res 51:945–956. https://doi.org/10.1194/jlr.M001016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kishibe M (2019) Physiological and pathological roles of kallikrein-related peptidases in the epidermis. J Dermatol Sci 95:50–55. https://doi.org/10.1016/j.jdermsci.2019.06.007

    Article  CAS  PubMed  Google Scholar 

  43. Ovaere P, Lippens S, Vandenabeele P, Declercq W (2009) The emerging roles of serine protease cascades in the epidermis. Trends Biochem Sci 34:453–463. https://doi.org/10.1016/j.tibs.2009.08.001

    Article  CAS  PubMed  Google Scholar 

  44. Lehner R, Quiroga AD (2016) Fatty acid handling in mammalian cells. Biochemistry of lipids, lipoproteins and membranes. Elsevier, Amsterdam, pp 149–184

    Chapter  Google Scholar 

  45. Amen N, Mathow D, Rabionet M et al (2013) Differentiation of epidermal keratinocytes is dependent on glucosylceramide:ceramide processing. Hum Mol Genet 22:4164–4179. https://doi.org/10.1093/hmg/ddt264

    Article  CAS  PubMed  Google Scholar 

  46. Hannun YA, Obeid LM (2018) Sphingolipids and their metabolism in physiology and disease. Nat Rev Mol Cell Biol 19:175–191. https://doi.org/10.1038/nrm.2017.107

    Article  CAS  PubMed  Google Scholar 

  47. Holleran WM, Takagi Y, Uchida Y (2006) Epidermal sphingolipids: metabolism, function, and roles in skin disorders. FEBS Lett 580:5456–5466. https://doi.org/10.1016/j.febslet.2006.08.039

    Article  CAS  PubMed  Google Scholar 

  48. Wennekes T, van den Berg RJBHN, Boot RG et al (2009) Glycosphingolipids-nature, function, and pharmacological modulation. Angew Chem Int Ed 48:8848–8869. https://doi.org/10.1002/anie.200902620

    Article  CAS  Google Scholar 

  49. van Smeden J, Janssens M, Gooris GS, Bouwstra JA (2014) The important role of stratum corneum lipids for the cutaneous barrier function. Biochim Biophys Acta 1841:295–313. https://doi.org/10.1016/j.bbalip.2013.11.006

    Article  CAS  PubMed  Google Scholar 

  50. Ishikawa J, Narita H, Kondo N et al (2010) Changes in the ceramide profile of atopic dermatitis patients. J Invest Dermatol 130:2511–2514. https://doi.org/10.1038/jid.2010.161

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Part of this study has received funding from the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT), under grant agreement No. 148.

Author information

Authors and Affiliations

  1. Institute of Plant Breeding and Genetic Resources, ELGO-DEMETER, 57001, Thessaloniki-Thermi, Greece

    Sophia Letsiou, Ioannis Ganopoulos, Aliki Xanthopoulou & Athanassios Molassiotis

  2. Institute of Olive Tree, Subtropical Crops and Viticulture (IOSV), Department of Vitis, ELGO-DEMETER, Lykovrysi, 14123, Athens, Greece

    Aliki Kapazoglou & Eirini Sarrou

  3. Laboratory of Pomology, Department of Horticulture, Aristotle University of Thessaloniki, 57001, Thessaloniki-Thermi, Greece

    Aliki Xanthopoulou

  4. Institute of Soil and Water Resources, ELGO-DEMETER, 57001, Thessaloniki-Thermi, Greece

    Georgia Tanou

  5. Joint Laboratory of Horticulture, ELGO-DEMETER, 57001, Thessaloniki-Thermi, Greece

    Georgia Tanou

Authors
  1. Sophia Letsiou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ioannis Ganopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aliki Kapazoglou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aliki Xanthopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eirini Sarrou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Georgia Tanou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Athanassios Molassiotis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sophia Letsiou.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

All authors agreed on publication.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 35 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Letsiou, S., Ganopoulos, I., Kapazoglou, A. et al. Probing the effects of sweet cherry (Prunus avium L.) extract on 2D and 3D human skin models. Mol Biol Rep 49, 2687–2693 (2022). https://doi.org/10.1007/s11033-021-07076-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-07076-4

Keywords

Search

Navigation