RESUMO
The skin keeps the human body healthy from extrinsic stimuli such as ultraviolet (UV) irradiation. However, chronic exposure of these stimuli reduces the number of proteins that constitute the extracellular matrix (ECM) and causes wrinkle formation. The amount of collagen, the main protein that constitutes connective tissue, is reduced in the human skin due to UV radiation. When human dermal fibroblasts were damaged by UVB, UVB increased the MMPs expressions and degraded type I collagen and other ECM proteins. Oyster (Crassostrea gigas) hydrolysate (OH) is known to have anticancer, antioxidant, and anti-apoptotic effects. To scrutinize the anti-wrinkle effect of the OH in the viewpoint of the balance between collagen degradation and synthesis, we conducted the study in UVB damaged human dermal fibroblasts. We determined type I procollagen, MMPs and related proteins using ELISA kit, qRT-PCR and western blot. In our study, we discovered that OH inhibits collagen degradation by regulating MAPKs, AP-1 and MMPs expression. Also, we found that OH promotes collagen production by enhancing TGFß receptor II expression and Smad3 phosphorylation. These results showed that OH regulates collagen degradation and stimulates collagen synthesis. Through this study, we found that OH is effective in inhibiting wrinkle formation and restore photo-aged human skin. It indicates that OH can be one of the functional materials in the fields of anti-wrinkle research.
Assuntos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Transcrição AP-1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Raios Ultravioleta , Animais , Colágeno/metabolismo , Humanos , Hidrólise , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Ostreidae , Pele/enzimologia , Pele/metabolismo , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiaçãoRESUMO
When the human skin is chronically exposed to external stimuli such as ultraviolet (UV) radiation, the skin tissue suffers damage and the structure of the extracellular matrix (ECM) in the skin is disrupted. This eventually causes symptoms such as wrinkles loss of elasticity, skin sagging, and skin cancer. We previously found that hydrolysate extracted from pacific oyster (Crassostrea gigas) is effective in improving wrinkle formation. In this study, we selected a pentapeptide that was expected to have the most wrinkle reduction effect among the various peptides in oyster hydrolysate through preliminary in vitro screening and examined whether the pentapeptide derived from oyster hydrolysate (OHP) is effective in reducing wrinkles in vivo. We investigated the wrinkle-reducing effect of the OHP through 18-week SKH-1 hairless mice model. Our results showed that the OHP reduces wrinkles lengths, depths, and epidermal thickness which were increased by UVB radiation, and restores the amount of collagen. The OHP recovered the activity of antioxidant enzymes and regulated the expression of proinflammatory cytokines. We also found that OHP increases the expression of type I collagen through stimulating the TGFß/Smad signaling pathway and inhibits the MMPs expression by regulating the MAPK/AP-1 signaling pathway. This study has shown that the OHP plays crucial roles in collagen production and wrinkle reduction in hairless mice and we proved the possibility of the OHP as a component for inhibiting wrinkle formation which was induced by photoaging.
Assuntos
Crassostrea/química , Peptídeos/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Animais , Colágeno Tipo I/metabolismo , Citocinas/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Epiderme/patologia , Feminino , Hidrólise , Hylobatidae , Camundongos , Camundongos Pelados , Peptídeos/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Envelhecimento da Pele/patologiaRESUMO
Chronic ultraviolet (UV) irradiation induces wrinkle formation. UV exposure increases reactive oxygen species (ROS) and upregulates the expression of matrix metalloproteinases (MMPs), which results in skin photoaging. Oyster (Crassostrea gigas), which is an abundant food resource in Asia and Europe, contains various sources of biological compounds and has several effects. Also, oyster hydrolysate (OH) has many biological activities. We investigated the inhibitory effects of OH on wrinkle formation in UVB-irradiated hairless mice. We induced UVB irradiation in hairless mice for 18 weeks and administered OH orally from the 9th week to the 18th week. We performed skin replicas and histological analyses in UVB-irradiated hairless mice dorsal skins. To determine the inhibitory mechanism of OH on wrinkle formation, we measured gene and protein expressions in dorsal skin using RT-qPCR and western blot analyses respectively. In our study, OH decreases wrinkle formation, epidermal thickness and collagen degradation in UVB-irradiated hairless mice. The gene expressions of MMPs were decreased and the gene expressions of collagen type I and TIMP-1 were increased in OH administered groups. Like gene expression tendencies, the protein expressions of MMPs were reduced and that of collagen type I was increased. Furthermore, the phosphorylation levels of ERK, JNK, and p38 were reduced in OH administered groups. We found that OH inhibits wrinkle formation, skin thickening, and collagen degradation by downregulating the MMP expression via the regulation of phosphorylation of MAPK. The results showed that OH significantly prevents UVB-induced photoaging in dorsal skin. Consistent with in vivo data, OH has potential as an anti-wrinkle agent.
Assuntos
Extratos Celulares/administração & dosagem , Extratos Celulares/farmacologia , Crassostrea/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Raios Ultravioleta , Administração Oral , Animais , Relação Dose-Resposta a Droga , Hidrólise , Masculino , Camundongos , Camundongos Pelados , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Pacific oyster (Crassostrea gigas) has been used to treat pigmentary disorders such as freckles, melasma, and moles in Korea. AIM OF THE STUDY: We aimed to investigate the inhibitory effects of oyster hydrolysate (OH) on melanogenesis in B16F10 melanoma cells and UVB-irradiated C57BL/6J mice. MATERIAL AND METHODS: The molecular weight distribution and peptide sequences of OH were detected using MALDI-TOF and UHPLC. To evaluate the anti-melanogenic effects of OH, cell viability, melanin content, tyrosinase activity, intracellular cyclic adenosine monophosphate (cAMP) and protein expressions levels were measured in B16F10 cells. In addition, OH was orally administered to UVB-irradiated mice for 9 weeks. After sacrificing the mice, the whitening effects of OH were evaluated based on histological observations and protein expression levels. RESULTS: In B16F10 cells, OH decreased melanin content and tyrosinase activity in a dose-dependent manner. OH exhibited anti-melanogenic activities via downregulation of cAMP signaling pathway, which consequently decreased melanin synthesis. In UVB-irradiated mice groups, OH decreased the number of active melanocytes and melanin granules. The expression of tyrosinase-related proteins and microphthalmia-associated transcription factor (MITF) decreased in the OH-administered groups. CONCLUSIONS: These results show that OH inhibits melanin synthesis in B16F10 cells via downregulation of cAMP signaling pathway and in UVB-irradiated mice, by decreasing the number of active melanocytes and melanin granules.