Asunto(s)
Epidermis/efectos de los fármacos , Hesperidina/administración & dosificación , Animales , Proliferación Celular , Epidermis/metabolismo , Hesperidina/química , Homeostasis , Concentración de Iones de Hidrógeno , Inflamación , Lípidos/química , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Permeabilidad , Antígeno Nuclear de Célula en Proliferación/metabolismo , Envejecimiento de la Piel , Fenómenos Fisiológicos de la Piel , Cicatrización de HeridasRESUMEN
Systemic and topical glucocorticoids (GC) can cause significant adverse effects not only on the dermis, but also on epidermal structure and function. In epidermis, a striking GC-induced alteration in permeability barrier function occurs that can be attributed to an inhibition of epidermal mitogenesis, differentiation and lipid production. As prior studies in normal hairless mice demonstrated that topical applications of a flavonoid ingredient found in citrus, hesperidin, improve epidermal barrier function by stimulating epidermal proliferation and differentiation, we assessed here whether its topical applications could prevent GC-induced changes in epidermal function in murine skin and the basis for such effects. When hairless mice were co-treated topically with GC and 2% hesperidin twice-daily for 9 days, hesperidin co-applications prevented the expected GC-induced impairments of epidermal permeability barrier homoeostasis and stratum corneum (SC) acidification. These preventive effects could be attributed to a significant increase in filaggrin expression, enhanced epidermal ß-glucocerebrosidase activity and accelerated lamellar bilayer maturation, the last two likely attributable to a hesperidin-induced reduction in stratum corneum pH. Furthermore, co-applications of hesperidin with GC largely prevented the expected GC-induced inhibition of epidermal proliferation. Finally, topical hesperidin increased epidermal glutathione reductase mRNA expression, which could counteract multiple functional negative effects of GC on epidermis. Together, these results show that topical hesperidin prevents GC-induced epidermal side effects by divergent mechanisms.
Asunto(s)
Clobetasol/efectos adversos , Clobetasol/antagonistas & inhibidores , Epidermis/efectos de los fármacos , Glucocorticoides/efectos adversos , Glucocorticoides/antagonistas & inhibidores , Hesperidina/administración & dosificación , Administración Tópica , Animales , Proliferación Celular/efectos de los fármacos , Clobetasol/administración & dosificación , Epidermis/patología , Epidermis/fisiopatología , Femenino , Proteínas Filagrina , Glucocorticoides/administración & dosificación , Glutatión Reductasa/genética , Proteínas de Filamentos Intermediarios/genética , Metabolismo de los Lípidos/efectos de los fármacos , Ratones , Ratones Pelados , Ratones Endogámicos C57BL , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The beneficial effects of certain herbal medicines on cutaneous function have been appreciated for centuries. Among these agents, chrysanthemum extract, apigenin, has been used for skin care, particularly in China, for millennia. However, the underlying mechanisms by which apigenin benefits the skin are not known. In this study, we first determined whether topical apigenin positively influences permeability barrier homoeostasis, and then the basis thereof. Hairless mice were treated topically with either 0.1% apigenin or vehicle alone twice daily for 9 days. At the end of the treatments, permeability barrier function was assessed with either an electrolytic water analyzer or a Tewameter. Our results show that topical apigenin significantly enhanced permeability barrier homoeostasis after tape stripping, although basal permeability barrier function remained unchanged. Improved barrier function correlated with enhanced filaggrin expression and lamellar body production, which was paralleled by elevated mRNA levels for the epidermal ABCA12. The mRNA levels for key lipid synthetic enzymes also were upregulated by apigenin. Finally, both cathelicidin-related peptide and mouse beta-defensin 3 immunostaining were increased by apigenin. We conclude that topical apigenin improves epidermal permeability barrier function by stimulating epidermal differentiation, lipid synthesis and secretion, as well as cutaneous antimicrobial peptide production. Apigenin could be useful for the prevention and treatment of skin disorders characterized by permeability barrier dysfunction, associated with reduced filaggrin levels and impaired antimicrobial defenses, such as atopic dermatitis.