Ginnalin B induces differentiation markers and modulates the proliferation/differentiation balance via the upregulation of NOTCH1 in human epidermal keratinocytes |
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| Affiliation: | 1. Department of Hospital Pharmacy, University of Toyama, Toyama 930-0194, Japan;2. Institute of Biological, Environmental and Rural Sciences/Phytoquest Limited, Plas Gogerddan, Aberystwyth, Ceredigion SY23 3EB, United Kingdom;3. Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3TA, United Kingdom;4. FUSHIMI Pharmaceutical Co. Ltd., Marugame, Kagawa 763-8605, Japan;1. Department of Cardiovascular Surgery, Toyohashi Heart Center, Toyohashi, Japan;2. Department of Cardiology, Toyohashi Heart Center, Toyohashi, Japan;1. Laboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, South Korea;2. College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae, Gyeongnam 50834, South Korea;1. School of Pharmacy, Chengdu Medical College, Chengdu 610500, China;2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China;3. Department of Gastroenterology, Chongzhou People’s Hospital, Chengdu 611230, China |
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| Abstract: | 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. |
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| Keywords: | Anhydrosugar Ginnalin B Keratinocyte Keratin 10 Differentiation |
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