Prospects of exogenous inositols in maintaining of skin, hair and nails condition: A review

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Abstract

Myoinositol (MI) and D-chiroinositol (DCI), used in the therapy of menstrual disorders, polycystic ovarian syndrome (PCOS), hirsutism, acne, gestational diabetes, and other diseases, are required for intracellular signal transduction from insulin and other hormone receptors. Clinical practice shows that, for instance, MI and DCI in the treatment of PCOS improve the condition of skin, hair, and nails. These effects of MI and DCI are related to the normalization of insulin signaling and support of differentiation and growth of various skin cell types (keratinocytes, fibroblasts, epitheliocytes, etc.). The effects of MI and DCI on the skin and its appendages, including in wound healing, can be enhanced by manganese, which provides an antioxidant effect and improves the connective tissue matrix of the skin, and folic acid, which is involved in amino acid metabolism, proliferation, and differentiation of dividing cells.

About the authors

Olga A. Gromova

Federal Research Center “Informatics and Management”

Author for correspondence.
Email: unesco.gromova@gmail.com
ORCID iD: 0000-0002-7663-710X

D. Sci. (Med.), Prof.

Russian Federation, Moscow

Ivan Yu. Torshin

Federal Research Center “Informatics and Management”

Email: tiy135@ccas.ru
ORCID iD: 0000-0002-2659-7998

Cand. Sci. (Chem.), Cand. Sci. (Phys.-Math.)

Russian Federation, Moscow

Nana K. Tetruashvili

Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology

Email: n_tetruashvili@oparina4.ru
ORCID iD: 0000-0002-9201-2281

D. Sci. (Med.)

Russian Federation, Moscow

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2. Fig. 1. Insulin receptor signaling cascades involved in skin repair during wound healing.

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3. Fig. 2. Topical insulin stimulates wound healing: a — typical images of wounds treated with 30 µl saline (control) or 0.03 IU of insulin in 30 µl saline; b — the use of insulin significantly increases the rate of wound surface closure (p<0,05).

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4. Fig. 3. MI-dependent activation by insulin of the Rac1 signaling protein that stimulates keratinocyte survival in cell culture. Cells were treated with 10-7 M insulin for 3 or 5 min. Insulin stimulates the translocation of Rac1 protein across the membrane (blue spots) and the membrane undulation of migrating cells (arrows).

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5. Fig. 4. Localization of the active form of AKT kinase in regenerating skin. Two major phosphorylated (i.e. activated by MI) forms of kinase: pAkt(Ser-473) and pAkt(Thr-308). Antibody staining, scale bar 50 mm; gt – granulation tissue; he – hyperproliferative epithelium; sc – superficial crust.

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6. Fig. 5. Electrotaxis of keratinocytes is performed via the PI3Kγ protein (Pik3cg gene): a – the injury causes lateral electric fields directed toward the center of the wound (red arrow), resulting from collapse of the local transepithelial potential difference (V). The black arrows indicate the dimensions and directions of the currents; b, c – disruption of keratinocyte electrotaxis. The red lines and blue arrows represent the trajectories and directions of cell movement. Pik3cg+/+ – normal, Pik3cg-/- – gene deletion; d–f – disruption of electrotaxis when the polarity of the electric field changes. When the field polarity is reversed, keratinocytes are removed from the wound area. In the case of gene deletion, there is no pronounced change in the movement direction.

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7. Fig. 6. Eicosanoid levels in skin cells when exposed to IF3, indomethacin or saline (*p<0.05; **p<0.01).

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8. Fig. 7. The enzyme Itpkb is involved in the propagation of the Ca2+ wave necessary for wound healing. The scale bar is 20 µm; the asterisks indicate the location of the wounds. Deletion of the Itpkb gene impairs Ca2+ wave propagation. Examples of Ca2+ wave propagation: damage to a control tissue sample (top), damage to a tissue sample from an animal with Itpkb deletion (center), and damage to a tissue sample from an animal with Itpkb deletion with 0.5 μmol/L IF4 added (bottom).

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9. Fig. 8. Upregulation of the IP3R3 receptor in rapidly renewing tissues: a – IP3R3 staining in small intestine epithelial cells. Black arrows indicate IP3R3 staining; blue arrows indicate no IP3R3 staining; b – IP3R3 staining is clearly visible in the hair follicle.

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10. Fig. 9. Hair cycle abnormalities in experimental deletion of the Itpr3 gene: a – side view, 5 weeks; b – hair morphology (bar 50 mm), more loose fibers in case of deletion; c, d – dorsal view, 8 weeks and 6 months; e – skin structure abnormalities, C – tail side, R – skull side; f – outer and inner sides of the skin in the Itpr3-/- deletion, with the red line indicating the boundary of the alopecia area; g – hematoxylin-eosin staining of the sagittal section of the dorsal skin at Itpr3-/- deletion.

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11. Fig. 10. Cytoskeletal abnormalities in the Itpr3 gene deletion in hair follicles: a – the root parts of many hairs in the telogen phase are covered by a serrated cuticle (asterisks) and are mixed with thicker anagen hairs covered by a smooth cuticle; b – normal hair follicle, * – hair, S – sebaceous glands; c – thin hair roots are quite rare (asterisks), hair channels are occupied by single hairs in anagen phase (thick arrows) or mixed hairs in anagen and telogen phases (thin arrows); d – keratin foliating (arrows) in gene deletion; e – hair follicle in gene deletion.

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12. Fig. 11. Synergism of MI/DСI and Mn in maintaining of skin, hair and nails condition.

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