NOVACUTAN PREPARATIONS AS POTENTIAL DERMATOGEROPROTECTORS: MOLECULAR-MICROSCOPIC STUDY

DOI: https://doi.org/10.29296/24999490-2021-04-06

Z.I. Gazitaeva(1, 2), A.O. Drobintseva(3), V.O. Polyakova(3), I.M. Kvetnoy(4), A.Yu. Prokopov(5) 1-Institute of Beauty Fijie, 7th Rostovsky Bystreet, 11, Moscow, 119121, Russian Federation; 2-St. Petersburg Institute of Bioregulation and Gerontology Russian Federation, Dynamo Ave. 3, St. Petersburg, 197110, Russian Federation; 3-St. Petersburg State Pediatric Medical University, Litovskaya Str. 2, St. Petersburg, 194100, Russian Federation; 4-Saint-Petersburg Federal Research Institute of Phthisiology and Pulmonology, Healthcare Ministry of Russia: Ligovskiy pr. 2–4, Saint-Petersburg, 191036, Russian Federation; 5ROS-Chimia Ltd, Pervomayskaya str, 15-705, Ekaterinburg, 620000, Russian Federation E-mail: [email protected]

Introduction. The work is devoted to study of new medication Novacutan SBio and Novacutan YBio as potential geroprotectors for biorevitalization of the skin. Klotho was used as a marker – to assess the overall aging of cells; MTH1 – the antioxidant status of cells; AR-1 – U.V. resistance of cells; synthetic activity of cells: elastin and collagen. The aim of the study was to compare the geroprotective properties of Novacutan YBio and Novacutan SBio. Methods. To study the aging of skin cells in culture, we used the method of combined cultivation of fibroblasts and keratinocytes of human skin, and to verify the expression of signaling molecules – aging markers – methods of immunocytochemistry and confocal microscopy. An in vitro experiment was performed to study of biopsies of the skin of patients after applying various therapies using Novacutan preparations. Results. We studied the expression of signaling molecules/markers AP-1, Klotho, Elastin, MTH-1 in samples of “young” and «old» cell cultures of human fibroblasts and keratinocytes when exposed to them with Novacutan YBio and Novacutan SBio. The authors showed a stimulating effect of Novacutan on the expression of markers Klotho, Elastin, MTH-1, and inhibitory effect on AP-1 expression during cell aging in cultures. Under in vitro conditions. Novacutan Y and S preparations were found to activate synthetic processes in the skin. In this case, the combination therapy of laser skin resurfacing with Novacutan biorevitalization courses is the most favorable. Conclusion. These studies allow considering the preparation Novacutan as a drug with pronounced general regulatory and dermatogeroprotective properties
Keywords: 
skin aging, biorevitalization, collagen, reparative processes, klotho protein, photoaging

Список литературы: 
  1. Vademecum vpervye podschital ob'em rynka «ukolov krasoty», VADEMECUM. 2017; 03. https://vademec.ru/projects/magazines/2017/03/ [Vademecum vpervye podschital ob’em rynka “ukolov krasoty” VADEMECUM.2017; 03 (in Russian)]
  2. Hess J., Angel P., Schorpp-Kistner M. AP-1 subunits: quarrel and harmony among siblings. J. of Cell Science. 2004; 117 (25): 5965–73.
  3. Baza znanij po biologii cheloveka. Onkogenetika. AP-1 transkriptsionnyj faktor: obschie svedenija. Data obraschenija: 01.10.2020 URL: http://humbio.ru/humbio/oncogenetics/000b3f5f.htm [Baza znanij po biologii cheloveka. Onkogenetika. AP-1 transcriptional factor: general information. 01.10.2020 (in Russian)]
  4. Qin Z., Robichaud P., He T., Fisher G.J., Voorhees J.J., Quan T. Oxidant exposure induces cysteine-rich protein 61 (CCN1) via c-Jun/AP-1 to reduce collagen expression in human dermal fibroblasts. PLoS One. 2014; 9 (12): e115402. https://doi.org/0.1371/journal.pone.0115402
  5. Hwang K.A., Yi B.R., Choi K.C. Molecular mechanisms and in vivo mouse models of skin aging associated with dermal matrix alterations. Send to Lab Anim. Res. 2011; 27 (1): 1–8.
  6. Kuro-o M., Matsumura Y., Aizawa H., Kawaguchi H., Suga T., Utsugi T., Ohyama Y., Kurabayashi M., Kaname T., Kume E., Iwasaki H., Iida A. «Mutation of the mouse klotho gene leads to a syndrome resembling ageing». Nature. 1997; 390 (6655): 45–51.
  7. Boksha I.S., Prohorova T.A., Savushkina O.K., Tereshkina E.B. Biohimija. 2017; 82 (9): 1278–95. [Boksha I.S., T.A. Prohorova, O.K. Savushkina, E.B. Tereshkina. Biochemistry. 2017; 82 (9): 1278–95 (in Russian)]
  8. Koyama D., Sato Y., Aizawa M., Maki T., Kurosawa M., Kuro-o M., Furukawa Y. Soluble αKlotho as a candidate for the biomarker of aging. Biochem Biophys Res Commun. 2015; 467 (4): 1019–25. https://doi.org/10.18632/aging.102771
  9. Dalton G.D., Xie J., An S.W., Huang C.L. New Insights into the Mechanism of Action of Soluble Klotho. Front Endocrinol. 2017; 17 (8): 323.
  10. Sopjani M., Rinnerthaler M., Kruja J., Dermaku-Sopjani M. Intracellular signaling of the aging suppressor protein Klotho. Curr Mol Med. 2015; 15 (1): 27–37.
  11. Sakumi K., Furuichi M., Tsuzuki T., Kakuma T., Kawabata S., Maki H., Sekiguchi M. Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis. The Journal of Biological Chemistry. 1993; 268 (31): 23524–30.
  12. Yoshimura D., Sakumi K., Ohno M., Sakai Y., Furuichi M., Iwai S., Nakabeppu Y. An oxidized purine nucleoside triphosphatase, MTH1, suppresses cell death caused by oxidative stress. J. Biol Chem. 2003; 278 (39): 37965–73.
  13. Rai P., Onder T., Young J. J.,. McFaline J.L, Pang B. Continuous elimination of oxidized nucleotides is necessary to prevent rapid onset of cellular senescence. Send to Proc Natl Acad Sci USA. 2009; 106 (1): 169–74.
  14. De Luca G., Ventura I., Sanghez V., Russo M.T., Ajmone-Cat M.A. Prolonged lifespan with enhanced exploratory behavior in mice overexpressing the oxidized nucleoside triphosphatase hMTH1. Aging Cell. 2013; 12 (4): 695–705.
  15. Avila Rodriguez M.I., Rodriguez Barroso L.G., Sánchez M.L. Collagen: A review on its sources and potential cosmetic applications. J Cosmet Dermatol. 2018; 17 (1): 20–6. https://doi.org/10.1111/jocd.12450.
  16. Zhang M., Hwang E., Lin P., Gao W., Ngo H.T.T., Yi T.H. Prunella vulgaris L. Exerts a Protective Effect Against Extrinsic Aging Through NF-κb, mapks, AP-1, and TGF-β/Smad Signaling Pathways in UVB-Aged Normal Human Dermal Fibroblasts. Rejuvenation Res. 2018; 21 (4): 313–22. https://doi.org/10.1089/rej.2017.1971
  17. Smirnova I.O. Fotostarenie kozhi i bazal'no-kletochnyj rak: rol' tuchnyh kletok. Klinicheskaja meditsina. 2005; 83 (7): 55–8. [Smirnova I.O. Skin photoaging and basal cell carcinoma: role of must cells. Klinicheskajamedicina. 2005; 83 (7): 55–8 (in Russian)]
  18. Tselujko C.C., Maljuk E.A., Korneeva L.S., Krasavina N.P. Morfofunktsional'naja harakteristika dermy kozhi i ee izmenenija pri starenii (obzor literatury). Bjulleten'. 2016; 60: 111–6. [Celujko C.C., Maljuk E.A., Korneeva L.S., Krasavina N.P. Morphofunctional characteristics of skin derma and its changing during aging (literature review) . Bjulleten’. 2016; 60: 111–6 (in Russian)]
  19. Zhang S., Duan E. Fighting against skin aging: the way from bench to bedside. Cell Transplant. 2018; 27 (5): 729–38. https://doi.org/10.1177/0963689717725755.
  20. Mora Huertas A.C., Schmelzer C.E., Hoehenwarter W., Heyroth F., Heinz A. Molecular-level insights into aging processes of skin elastin. Biochimie. 2016; 128–129: 163–73. https://doi.org/10.1016/j.biochi.2016.08.010.
  21. Gazitaeva Z.A., Drobintseva A.O., Chang J, Poljakova V.O., Kvetnoj I.M. Molekuljarnye mehanizmy dermal'nogo geroprotektivnogo dejstvija preparatov na osnove biomimeticheskih peptidov. Molekuljarnaja meditsina. 2015; 5: 16–9. [Gazitaeva Z.A., Drobintseva A.O, CHang J, Polyakova V.O., Kvetnoj I.M. Molecular mecanisms dermal geroprotector action preparations consisting of biomimetical peptides. Molekulyarnaya meditsina. 2015; 5: 16–9 (in Russian)]