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The Effect of the Geroprotectors Astragaloside IV, Cycloastragenol, and Timovial–Epivial Peptide Complex on Telomere Length and Telomerase Activity in Human Mesenchymal Stromal Cells and Senescent Fibroblasts

Cell and Tissue Biology volume 14, pages 83–90 (2020)Cite this article

Abstract—

A search for geroprotectors that would affect the telomere length and/or telomerase activity and not exhibit tumorigenicity is under progress. The medical use of various extracts of plants from the Astragalus genus of the Fabaceae family was first described in 200 CE. However, scientific studies of the components of these extracts (cycloastragenol, astragaloside IV) have begun only recently. The goal of this work was to explore the effect of a composition consisting of astragaloside IV, cycloastragenol, and the Timovial–Epivial dipeptide and its components on telomere length and telomerase activity in human umbilical cord mesenchymal stromal cells and aging fibroblasts. Telomerase activity was determined by the telomeric repeat amplification protocol (TRAP). Telomere length was determined by measuring the intensity of fluorescence in situ hybridization signals using flow cytometry. None of the composition components caused a significant change in the determined parameters on its own. Only cycloastragenol had a negligible effect on the telomere length in fibroblasts. The combination of the key compound, astragaloside IV, aglycone of astragalosides—cycloastragenol (CAG), and biopeptide complex produced more significant changes in the telomere length and telomerase activity than did each component alone. The complex was shown to have a significant effect on telomere length and telomerase activity. Further studies are needed to determine the mechanism of the effect of the components combination on telomere length and telomerase activity.

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Funding

This work was carried out as part of a state order of the Ministry of Health of the Russian Federation (Enukashvily N.I., Skazina M.A., telomere length and telomerase activity evaluation) and with financial support from the Russian Science Foundation, project no. 19-74-20102 (Chubar A.V., cell culture work).

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Authors and Affiliations

  1. Institute of Cytology, Russian Academy of Sciences, 194064, St. Petersburg, Russia

    N. I. Enukashvily & A. V. Chubar

  2. Pokrovsky Stem Cell Bank, 199106, St. Petersburg, Russia

    M. A. Skazina

  3. Northwestern State Medical University Named after I.I. Mechnikov, 195067, St. Petersburg, Russia

    N. I. Enukashvily & M. A. Skazina

  4. Promomed LLC, 12909, Moscow, Russia

    A. B. Mashutin

  5. Department of Drug Registration of the Department of State Regulation of Drugs, Ministry of Health, 107045, Moscow, Russia

    A. B. Mashutin

Authors
  1. N. I. Enukashvily
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  2. M. A. Skazina
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  3. A. V. Chubar
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  4. A. B. Mashutin
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Correspondence to N. I. Enukashvily.

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in the study involving human beings complied with the ethical standards of the institutional and/or national research ethics committee and the 1964 Helsinki Declaration and its subsequent changes or comparable ethical standards. Informed voluntary consent was obtained from each of the participants in the study (donors of cells- , cultured MSC, and HF).

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Translated by I. Fridlyanskaya

Abbreviations: DMSO—dimethyl sulfoxide, MSC UC—mesenchymal stromal cell of umbilical cord, HF—human fibroblast, CAG—cycloastragenol, CREB—cAMP response element binding protein, hTERT—human telomerase reverse transcriptase, TERC—telomerase RNA component, TRAP—telomeric repeat amplification.

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Enukashvily, N.I., Skazina, M.A., Chubar, A.V. et al. The Effect of the Geroprotectors Astragaloside IV, Cycloastragenol, and Timovial–Epivial Peptide Complex on Telomere Length and Telomerase Activity in Human Mesenchymal Stromal Cells and Senescent Fibroblasts. Cell Tiss. Biol. 14, 83–90 (2020). https://doi.org/10.1134/S1990519X20020030

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  • DOI: https://doi.org/10.1134/S1990519X20020030

Keywords:

  • telomeres
  • astragalus
  • cycloastragenol
  • telomerase
  • mesenchymal stromal cells
  • fibroblasts
  • geroprotectors