RESUMO
Low molecular weight collagen peptide (LMWCP) is a collagen hydrolysate derived from fish. We investigated the effects of LMWCP on hair growth using human dermal papilla cells (hDPCs), human hair follicles (hHFs), patch assay, and telogenic C57BL/6 mice, while also examining the underlying mechanisms of its action. LMWCP promoted proliferation and mitochondrial potential, and the secretion of hair growth-related factors, such as EGF, HB-EGF, FGF-4, and FGF-6 in hDPCs. Patch assay showed that LMWCP increased the neogeneration of new HFs in a dose-dependent manner. This result correlated with an increase in the expression of dermal papilla (DP) signature genes such as, ALPL, SHH, FGF7, and BMP-2. LMWCP upregulated phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin, and nuclear translocation of ß-catenin, and it increased the expression of Wnt3a, LEF1, VEGF, ALP, and ß-catenin. LMWCP promoted the growth of hHFs and increased the expression of ß-catenin and VEGF. Oral administration of LMWCP to mice significantly stimulated hair growth. The expression of Wnt3a, ß-catenin, PCNA, Cyclin D1, and VEGF was also elevated in the back skin of the mice. Furthermore, LMWCP increased the expression of cytokeratin and Keratin Type I and II. Collectively, these findings demonstrate that LMWCP has the potential to increase hair growth via activating the Wnt/ß-catenin signaling pathway.
Assuntos
Via de Sinalização Wnt , beta Catenina , Camundongos , Humanos , Animais , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Peso Molecular , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Cultivadas , Camundongos Endogâmicos C57BL , Folículo Piloso , Cabelo , Proliferação de CélulasRESUMO
This study reveals that low-molecular-weight collagen peptide (LMWCP) can stimulate the differentiation and the mineralization of MC3T3-E1 cells in vitro and attenuate the bone remodeling process in ovariectomized (OVX) Sprague-Dawley rats in vivo. Moreover, the assessed LMWCP increased the activity of alkaline phosphatase (ALP), synthesis of collagen, and mineralization in MC3T3-E1 cells. Additionally, mRNA levels of bone metabolism-related factors such as the collagen type I alpha 1 chain, osteocalcin (OCN), osterix, bone sialoprotein, and the Runt family-associated transcription factor 2 were increased in cells treated with 1,000 µg/ml of LMWCP. Furthermore, we demonstrated that critical bone morphometric parameters exhibited significant differences between the LMWCP (400 mg/kg)-receiving and vehicle-treated rat groups. Moreover, the expression of type I collagen and the activity of ALP were found to be higher in both the femur and lumbar vertebrae of OVX rats treated with LMWCP. Finally, the administration of LMWCP managed to alleviate osteogenic parameters such as the ALP activity and the levels of the bone alkaline phosphatase, the OCN, and the procollagen type 1 N-terminal propeptide in OVX rats. Thus, our findings suggest that LMWCP is a promising candidate for the development of food-based prevention strategies against osteoporosis.
Assuntos
Fosfatase Alcalina , Osteoblastos , Ratos , Animais , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/farmacologia , Ratos Sprague-Dawley , Colágeno/metabolismo , Peptídeos/farmacologia , Osteogênese , Osteocalcina/genética , Osteocalcina/metabolismo , Osteocalcina/farmacologia , Diferenciação CelularRESUMO
Although blackcurrant has several health benefits, such as antioxidant and anti-inflammatory properties, its effects on the retina remain unclear. In this study, we investigated the efficacy of black currant extract (BCE) in an in vitro and in vivo model of dry age-related macular degeneration (AMD) induced by blue light. Dry macular degeneration is characterized by the abnormal accumulation of lipofuscin (e.g., N-retinylidene-N-retinylethanolamine, A2E) in the retina. Blue light (BL) significantly decreased the viability of A2E-laden human retinal pigment epithelial cells (ARPE-19). However, BCE treatment protected ARPE-19 cells from A2E and BL. A2E, which is oxidized by blue light, generates reactive oxygen species in RPE cells. Treatment with BCE significantly decreased (80.8%) reactive oxygen species levels induced by A2E and BL in a concentration-dependent manner. BCE inhibited A2E accumulation in ARPE-19 cells and significantly downregulated the expression of genes increased by A2E and BL in ARPE-19 cells. In vivo, oral administration of BCE (25-100 mg/kg) ameliorated ocular lesions of BL-induced retinal damage in a mouse model and rescued the thickness of the whole retina, photoreceptor segment layer, outer nuclear layer, and inner nuclear layer. The decrease in the number of nuclei in the outer nuclear layer induced by BL was also rescued by BCE. Additionally, BCE administration rescued (40.0%) the BL-induced reduction in the expression level of superoxide dismutase 1. Taken together, our results suggest that BCE may have preventive and therapeutic effects on dry AMD through its antioxidant activity and inhibition of lipofuscin accumulation in the retina.
RESUMO
The glycation process has been recognized as one of the critical parameters that accelerate signs of skin aging, especially in skin exposed to environment factors, such as ultraviolet radiation. Although previous studies showed the anti-inflammatory and antiaging properties of the hydrolyzed collagen tripeptide (CTP), its exact mechanism is not fully understood. Therefore, in this study, we sought to investigate the effect of a topical CTP on facial skin. Our group designed a 4 week prospective, single-arm study of 22 Asian women who applied topical CTP. We observed significant improvements in skin wrinkles, elasticity, and density with a reduction in skin accumulation of advanced glycated end products (AGEs) at week 4 without any adverse effects. The in vitro study revealed a preventive effect of the topical CTP on the accumulation of AGEs, denatured collagen production, and reactive oxygen species in dermal fibroblasts. Moreover, treatment with the CTP decreased induction of matrix metalloproteinases while increasing the collagen 1 level. These results suggest that the application of a topical CTP might improve clinical aging phenotypes via the inhibition of glycation and oxidative stress, leading to a delay in cellular aging.
Assuntos
Senescência Celular/efeitos dos fármacos , Colágeno/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Estresse Oxidativo , Fragmentos de Peptídeos/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Adulto , Estudos de Casos e Controles , Elasticidade , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Glicosilação , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Espécies Reativas de Oxigênio/metabolismo , Pele/metabolismo , Envelhecimento da Pele/patologiaRESUMO
This study examined whether the oral administration of low-molecular-weight collagen peptide (LMCP) containing 3% Gly-Pro-Hyp with >15% tripeptide (Gly-X-Y) content could ameliorate osteoarthritis (OA) progression using a rabbit anterior cruciate ligament transection (ACLT) model of induced OA and chondrocytes isolated from a patient with OA. Oral LMCP administration (100 or 200 mg/kg/day) for 12 weeks ameliorated cartilage damage and reduced the loss of proteoglycan compared to the findings in the ACLT control group, resulting in dose-dependent (p < 0.05) improvements of the OARSI score in hematoxylin & eosin (H&E) and Safranin O staining. In microcomputed tomography analysis, LMCP also significantly (p < 0.05) suppressed the deterioration of the microstructure in tibial subchondral bone during OA progression. The elevation of IL-1ßand IL-6 concentrations in synovial fluid following OA induction was dose-dependently (p < 0.05) reduced by LMCP treatment. Furthermore, immunohistochemistry illustrated that LMCP significantly (p < 0.05) upregulated type II collagen and downregulated matrix metalloproteinase-13 in cartilage tissue. Consistent with the in vivo results, LMCP significantly (p < 0.05) increased the mRNA expression of COL2A1 and ACAN in chondrocytes isolated from a patient with OA regardless of the conditions for IL-1ßinduction. These findings suggest that LMCP has potential as a therapeutic treatment for OA that stimulates cartilage regeneration.
Assuntos
Condrócitos/metabolismo , Colágeno/uso terapêutico , Matriz Extracelular/metabolismo , Osteoartrite/tratamento farmacológico , Agrecanas , Animais , Ligamento Cruzado Anterior , Células Cultivadas , Colágeno Tipo II , Citocinas , Modelos Animais de Doenças , Humanos , Masculino , Metaloproteinase 13 da Matriz , Peso Molecular , Peptídeos/uso terapêutico , Coelhos , Líquido SinovialRESUMO
Licorice, the root of Glycyrrhiza glabra, has been observed to possess an anti-obesity effect. Previous research has suggested that licorice acetone extract (LE) has an influence on mitotic clonal expansion (MCE) and adenosine monophosphate-activated protein kinase (AMPK), which play a key role in regulating adipogenesis. This study sought further insight into the molecular mechanism of LE's anti-obesity effect using 3T3-L1 adipocytes in vitro. LE inhibited 3T3-L1 adipogenesis, and the inhibitory effect of LE on adipogenesis was most significant in the early stage of adipogenic differentiation. LE inhibited the protein expression of cyclins and cyclin-dependent kinases in the MCE stage and arrested cells in the G1 phase of the cell cycle. Furthermore, it activated AMPK via phosphorylation. Moreover, the expression levels of lipid metabolism-related genes were regulated by LE. These findings suggest the anti-obesity effect of LE via MCE and AMPK regulation. PRACTICAL APPLICATIONS: Although the anti-obesity effects of licorice have been studied, the application of functional food-related anti-obesity effects of licorice has been less than that of other extracts. The present study increases the reliability of the anti-obesity effect of licorice by suggesting a new mechanism of action and expands the application of functional foods related to the anti-obesity effect of licorice. A new mechanistic insight will not only improve the scientific knowledge but will also help to predict the side effects of licorice's anti-obesity application.