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Bioorg Med Chem ; 27(11): 2172-2180, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-31005366

RESUMEN

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.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Receptor Notch1/metabolismo , Piel/efectos de los fármacos , Sorbitol/análogos & derivados , Antígenos de Diferenciación/metabolismo , Línea Celular , Proteínas Filagrina , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Proteínas de Filamentos Intermediarios/metabolismo , Queratina-1/metabolismo , Queratina-10/metabolismo , Sorbitol/farmacología
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