RESUMO
Zingerone is a non-volatile compound found mainly in dried ginger. Zingerone increases the expression of osteogenic markers and has antioxidant effects. A previous study showed that zingerone accelerated osteoblast differentiation by suppressing the expression of Smad7, a member of the inhibitory Smad (I-Smad) family. However, it is not known if zingerone can induce osteoblast differentiation by regulating Smad1/5/9, a member of the receptor-regulated Smad (R-Smad) family. In addition, osteoblast differentiation induced by Smad1/5/9 mediated increases in the expression of heme oxygenase 1 (HO-1) has not been reported. This study investigated the effects of zingerone on osteoblast differentiation and confirmed the relationship between Smad1/5/9 and HO-1. Zingerone increased the expression of osteogenic genes including runt-related transcription factor 2 (Runx2), distal-less homeobox (Dlx5) and osteocalcin (OC) and also promoted Smad1/5/9 phosphorylation. Interestingly, HO-1 expression was also elevated by zingerone, and an inhibitor of HO-1 (Sn[IV] protoporphyrin IX dichloride [SnPP]) suppressed the zingerone-induced increase in HO-1 expression and expression of osteogenic marker genes such as Dlx5, Runx2 and OC. Protein phosphatase 2A Cα (PP2A Cα, an inhibitor of Smad1/5/9) suppressed the zingerone-induced increase in HO-1 expression and expression of osteogenic marker genes. The zingerone-induced increase in HO-1 luciferase activity was suppressed by PP2A Cα. Taken together; our data demonstrate that zingerone promotes osteoblast differentiation by increasing Smad1/5/9 mediated HO-1 expression.
Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core , Osteoblastos , Animais , Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/farmacologia , Guaiacol/análogos & derivados , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Camundongos , Osteocalcina , Osteogênese , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Proteína Smad1/metabolismo , Fatores de Transcrição/metabolismoRESUMO
The effects of Lavandula angustifolia extract fermented with Pediococcus pentosaceus DK1 on UVB-mediated MMP-1 expression and collagen decrease in human skin fibroblasts were determined, and the conversion of its components was also analyzed. Fermentation was performed at varying L. angustifolia extract and MRS medium concentrations, and optimal fermentation conditions were selected. L. angustifolia extracts showed decreased cytotoxicity after fermentation in the fibroblasts. UVB-irradiated fibroblasts treated with fermented L. angustifolia extract showed MMP-1 expression 8.2-14.0% lower than that in UVB-irradiated fibroblasts treated with non-fermented extract. This was observed even at fermented extract concentrations lower than those of non-fermented extracts. Fibroblasts treated with fermented L. angustifolia extract showed 20% less reduction in collagen production upon UVB irradiation than those treated with non-fermented extracts. UVB-irradiated fibroblasts treated with fermented L. angustifolia extracts showed 50% higher inhibition of ROS generation than those treated with non-fermented extract. Luteolin and apigenin glycosides of L. angustifolia were converted during fermentation, and identified using RP-HPLC and LC/ESI-MS. Therefore, the effects of L. angustifolia extract on MMP-1 expression and collagen decrease in UVB-irradiated human skin fibroblasts were increased through fermentation by P. pentosaceus.
Assuntos
Diospyros/microbiologia , Lavandula/química , Pediococcus pentosaceus/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Protetores contra Radiação/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Linhagem Celular , Colágeno Tipo I/metabolismo , Fermentação , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Frutas/microbiologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos da radiação , Humanos , Metaloproteinase 1 da Matriz/genética , Pró-Colágeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Envelhecimento da Pele/genética , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversosRESUMO
In this study, we prepared double cross-linked interpenetrating polymer network (IPN) hydrogels composed of temperature sensitive poly (N-isopropylacrylamide) (PNIPAM) and pH sensitive hyaluronic acid (HA) by radical polymerization and Michael addition. Their physicochemical properties for transdermal delivery of luteolin inhibiting the hyperproliferation of keratinocytes in psoriasis were investigated and drug release studies were performed. Double networks of HA/PNIPAM IPN hydrogel were identified through FT-IR and 13CNMR. By measuring the swelling ratios pH and temperature sensitivity were confirmed, and it was influenced by the content of a cross-linking agent. As a result of texture analysis and rheometry, a IPN hydrogel with 3% crosslinker content had the most adhesive and stable cross-linked network. Therefore, luteolin was loaded on this hydrogel. Its drug release behavior was determined at various temperatures and pH using several drug release kinetic models. As a result of skin permeation study, HA/PNIPAM IPN hydrogel effectively delivers luteolin to the epidermis and dermis. No toxicity was observed as a result of observing cytotoxicity of the hydrogel for application to the skin. In conclusion, IPN hydrogels can be developed as carriers of transdermal delivery system of luteolin for psoriasis skin relief.
