Ginnalin B induces differentiation markers and modulates the proliferation/differentiation balance via the upregulation of NOTCH1 in human epidermal keratinocytes
| Autor: | Chihiro Takeuchi, Fumihiro Ishikawa, Shuki Imaeda, Atsushi Kato, Megumi Shintani, George W. J. Fleet, Junna Koyama, Isao Adachi, Kenta Shinzawa, Robert J. Nash |
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| Rok vydání: | 2019 |
| Předmět: |
Keratinocytes
Clinical Biochemistry Pharmaceutical Science Human skin Filaggrin Proteins 01 natural sciences Biochemistry Cell Line Intermediate Filament Proteins Downregulation and upregulation Drug Discovery Keratin medicine Humans Sorbitol Receptor Notch1 Molecular Biology Cell Proliferation Skin chemistry.chemical_classification Epidermis (botany) biology 010405 organic chemistry Organic Chemistry Ceramide synthase 3 Cell Differentiation Keratin-10 Keratin 1 Antigens Differentiation G1 Phase Cell Cycle Checkpoints 0104 chemical sciences Cell biology 010404 medicinal & biomolecular chemistry medicine.anatomical_structure chemistry biology.protein Molecular Medicine Keratin-1 Keratinocyte Filaggrin |
| Zdroj: | Bioorganic & Medicinal Chemistry. 27:2172-2180 |
| ISSN: | 0968-0896 |
| Popis: | The red maple and sugar maple (Acer rubrum and A. saccharum, respectively) contain acertannins (ginnalins and maplexins), galloylated derivatives of 1,5-anhydro- d -glucitol (1,5-AG, 1). These compounds have a variety of potential medicinal properties and we have shown that some of them promote the expression of ceramide synthase 3. We now report on the beneficial effects of ginnalin B, (6-O-galloyl-1,5-AG, 5), leading to acceleration of skin metabolism and reduction of the turnover time. Ginnalin B dose-dependently increased the relative amount of keratin 10, keratin 1, and filaggrin gene, with maximal increase of 1.7-, 2.9, and 5.2-fold at 100 μM, respectively. The validation study showed that it had superior capacity to induce multiple stages of keratinocyte differentiation and significantly elevated the immunostaining site of keratin 10 and filaggrin in a 3-dimensional cultured human skin model, by 1.2 and 2.8-fold, respectively. Furthermore, ginnalin B caused the arrest of proliferation at the G0/G1 phase but it did not induce apoptotic cell death in normal human keratinocytes. Molecular studies revealed that ginnalin B up-regulated the levels of NOTCH1 and a concomitant increase p21 expression. Ginnalin B, therefore, represents a new class of promising functional and medical cosmetic compound and it could contribute to the maintenance of homeostasis of the epidermis. |
| Databáze: | OpenAIRE |
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