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1.
Genes Genomics ; 46(1): 13-25, 2024 Jan.
Article En | MEDLINE | ID: mdl-37971618

BACKGROUND: The skin microbiome, a diverse community of microorganisms, plays a crucial role in maintaining skin health. Among these microorganisms, the gram-positive bacterium Micrococcus luteus exhibits potential for promoting skin health. This study focuses on postbiotics derived from M. luteus YM-4, a strain isolated from human skin. OBJECTIVE: Our objective is to explore the beneficial effects of YM-4 culture filtrate on dermatological health, including enhancing barrier function, modulating immune response, and aiding recovery from environmental damage. METHODS: The effects of the YM-4 culture filtrate were tested on human keratinocytes and fibroblasts under various conditions using real-time PCR for gene expression analysis and fibroblast migration assays. A dehydration-simulated model was employed to prepare RNA-Seq samples from HaCaT cells treated with the YM-4 culture filtrate. Differentially expressed genes were identified and functionally classified through k-means clustering, gene ontology terms enrichment analyses, and protein-protein interactions mapping. RESULTS: The YM-4 culture filtrate enhanced the expression of genes involved in skin hydration, hyaluronic acid synthesis, barrier function, and cell proliferation. It also reduced inflammation markers in keratinocytes and fibroblasts under stress conditions. It mitigated UVB-induced collagen degradation while promoted collagen synthesis, suggesting anti-aging properties, and accelerated wound healing processes by promoting cell proliferation and migration. RNA sequencing analysis revealed that the YM-4 culture filtrate could reverse dehydration-induced transcriptional changes towards a state similar to untreated cells. CONCLUSION: M. luteus YM-4 culture filtrate exhibits significant therapeutic potential for dermatological applications.


Dehydration , Epirubicin/analogs & derivatives , Micrococcus luteus , Humans , Dehydration/metabolism , Skin/metabolism , Collagen/metabolism
2.
Skin Res Technol ; 29(11): e13518, 2023 Nov.
Article En | MEDLINE | ID: mdl-38009026

AIMS: Oriental herbs have been used as medicines in the folk remedy for their numerous phytochemicals and bioactivities. In this study, we have selected five Korean traditional medical herbs and applied bio conversion extraction technology, named it as Bioconversion Oji complex, to identify phytochemicals and evaluate skin related efficacies. MATERIAL AND METHODS: The process of two-step bio conversion was sequentially conducted. The first step of fermentation was to produce biosurfactants using macadamia seed oil with Candida bombicola, and then five natural plants were added to carry out the main fermentation. To evaluate skin improvement efficacy of Bioconversion Oji complex, in vitro and in vivo studies were conducted. We studied HaCaT cells cultured to assess viability, skin anti-inflammatory, moisturizing and barrier improvement-related mRNA expression. For efficacy study, 21 participants were tested evaluating anti-inflammatory, skin moisturizing and skin barrier improving effects of Bioconversion Oji complex compared to Water extraction of Oji (placebo) for the 4 weeks test period. RESULTS: The application of bioconversion technology highly increased the content of amino acids and lipids within Bioconversion Oji complex, and 23 flavonoids were also identified. Bioconversion Oji complex was found to be non-toxic and showed significant effects in all parameters tested, including anti-inflammation, skin moisture, and skin barrier in both in vitro and in clinical studies. CONCLUSIONS: Bioconversion Oji complex has demonstrated skin-friendly properties with significant beneficial effects on anti-inflammatory, skin hydration and barrier function properties. This study provides evidence for the use of Bioconversion Oji complex as an active ingredient in cosmetics and skincare products.


Saccharomyces cerevisiae , Skin , Humans , Fermentation , Anti-Inflammatory Agents/pharmacology
3.
J Dermatol Sci ; 109(2): 61-70, 2023 Feb.
Article En | MEDLINE | ID: mdl-36725458

BACKGROUND: Cannabidiol, a non-psychoactive phytocannabinoid, has antioxidant and anti-inflammatory activity in keratinocytes. However, the signaling pathway through which cannabidiol exerts its effect on keratinocytes or whether it can modulate keratinocyte differentiation has not been fully elucidated yet. OBJECTIVE: We investigated whether cannabidiol modulates epidermal differentiation and scavenges reactive oxygen species through the aryl hydrocarbon receptor (AhR) in keratinocytes and epidermal equivalents. METHODS: We investigated the cannabidiol-induced activation of AhR using AhR luciferase reporter assay, qRT-PCR, western blot, and immunofluorescence assays. We also analyzed whether keratinocyte differentiation and antioxidant activity are regulated by cannabidiol-induced AhR activation. RESULTS: In both keratinocytes and epidermal equivalents, cannabidiol increased both the mRNA and protein expression of filaggrin, involucrin, NRF2, and NQO1 and the mRNA expression of the AhR target genes, including CYP1A1 and aryl hydrocarbon receptor repressor. Additionally, cannabidiol showed antioxidant activity that was attenuated by AhR knockdown or co-administration with an AhR antagonist. Moreover, cannabidiol increased the ratio of OVOL1/OVOL2 mRNA expression, which is a downstream regulator of AhR that mediates epidermal differentiation. In addition to increased expression of barrier-related proteins, cannabidiol-treated epidermal equivalent showed a more prominent granular layer than the control epidermis. The increased granular layer by cannabidiol was suppressed by the AhR antagonist. CONCLUSION: Cannabidiol can be a modulator of the AhR-OVOL1-filaggrin axis and AhR-NRF2-NQO1 signaling, thus indicating a potential use of cannabidiol in skin barrier enhancement and reducing oxidative stress.


Cannabidiol , Epidermis , Keratinocytes , Receptors, Aryl Hydrocarbon , Antioxidants/pharmacology , Antioxidants/metabolism , Cannabidiol/pharmacology , Cannabidiol/metabolism , Epidermis/drug effects , Epidermis/metabolism , Filaggrin Proteins , Homeostasis/drug effects , Keratinocytes/drug effects , Keratinocytes/metabolism , NF-E2-Related Factor 2/metabolism , Oxidation-Reduction/drug effects , Receptors, Aryl Hydrocarbon/metabolism , RNA, Messenger/metabolism , Signal Transduction , Cell Differentiation/drug effects , Cell Differentiation/physiology
4.
Int J Mol Sci ; 21(22)2020 Nov 10.
Article En | MEDLINE | ID: mdl-33182726

In recent years, a number of active materials have been developed to provide anti-aging benefits for skin and, among them, peptides have been considered the most promising candidate due to their remarkable and long-lasting anti-wrinkle activity. Recent studies have begun to elucidate the relationship between the secretion of emotion-related hormones and skin aging. Kisspeptin, a neuropeptide encoded by the KISS1 gene, has gained attention in reproductive endocrinology since it stimulates the reproductive axis in the hypothalamus; however, the effects of Kisspeptin on skin have not been studied yet. In this study, we synthesized Kisspeptin-10 and Kisspeptin-E, which are biologically active fragments, to mimic the action of Kisspeptin. Next, we demonstrated the anti-aging effects of the Kisspeptin-mimicking fragments using UV-induced skin aging models, such as UV-induced human dermal fibroblasts (Hs68) and human skin explants. Kisspeptin-E suppressed UV-induced 11 beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) stimulation leading to a regulation of skin aging related genes, including type I procollagen, matrix metalloproteinases-1 (MMP-1), interleukin-6 (IL-6), and IL-8, and rescued the skin integrity. Taken together, these results suggest that Kisspeptin-E could be useful to improve UV-induced skin aging by modulating expression of stress related genes, such as 11ß-HSD1.


Kisspeptins/chemical synthesis , Kisspeptins/pharmacology , Skin Aging/drug effects , 11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors , 11-beta-Hydroxysteroid Dehydrogenase Type 1/genetics , Cell Line , Collagen Type I/genetics , Collagen Type I/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Expression/drug effects , Humans , Interleukin-6/genetics , Interleukin-6/metabolism , Interleukin-8/genetics , Interleukin-8/metabolism , Kisspeptins/chemistry , Kisspeptins/genetics , Kisspeptins/physiology , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 1/metabolism , Models, Biological , Models, Molecular , Molecular Mimicry , Molecular Structure , Peptide Fragments/chemical synthesis , Peptide Fragments/chemistry , Peptide Fragments/pharmacology , Protein Conformation , RNA, Messenger/genetics , RNA, Messenger/metabolism , Skin/drug effects , Skin/metabolism , Skin Aging/genetics , Skin Aging/physiology , Skin Physiological Phenomena , Solid-Phase Synthesis Techniques , Tissue Culture Techniques , Ultraviolet Rays/adverse effects
5.
Int J Mol Sci ; 21(9)2020 May 11.
Article En | MEDLINE | ID: mdl-32403430

In this study, caviar (sturgeon eggs) was used to elucidate its roles in adiponectin production and skin anti-aging. Recently, caviar has been largely used not only as a nutritional food, but also in cosmetic products. In particular, it has been reported that docosahexaenoic acid (DHA), as one of the main phospholipid components of caviar extract, induces intracellular lipid accumulation and the expression of adiponectin in adipocytes. Although adipocytes are well known to be associated with the skin dermis by secreting various factors (e.g., adiponectin), the effects of caviar extract and DHA on the skin are not well studied. Here, we demonstrate the effects of caviar extract and DHA on adipocyte differentiation and adiponectin production, resulting in a preventive role in UV-irradiated skin aging. Caviar extract and DHA enhanced adipocyte differentiation and promoted the synthesis of transcription factors controlling adipocyte differentiation and adiponectin. In addition, the mRNA expression levels of matrix metalloproteinase-1 (MMP-1) were decreased in UVB-irradiated Hs68 fibroblasts that were cultured in conditioned medium from caviar extract or DHA-treated differentiated adipocytes. Taken together, these results indicate that caviar extract and DHA induce adipocyte differentiation and adiponectin production, thereby inhibiting UVB-induced premature skin aging via the suppression of MMP-1 production.


Adipocytes/drug effects , Adiponectin/metabolism , Docosahexaenoic Acids/pharmacology , Eggs/analysis , Fibroblasts/drug effects , 3T3-L1 Cells , Adipocytes/cytology , Adipocytes/metabolism , Animals , Cell Differentiation/drug effects , Cell Line , Fibroblasts/metabolism , Fibroblasts/radiation effects , Fish Products , Foreskin/cytology , Foreskin/drug effects , Foreskin/radiation effects , Gene Expression/drug effects , Gene Expression/radiation effects , Humans , Male , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 1/metabolism , Mice , Skin Aging/drug effects , Skin Aging/radiation effects , Ultraviolet Rays
6.
Integr Cancer Ther ; 18: 1534735419851197, 2019.
Article En | MEDLINE | ID: mdl-31109222

AIM: To evaluate the anti-invasive effect of ethanol extracts of rhizome of Dryopteris crassirhizoma (EEDC) in matrix invasion and formation of functional invadopodia and to determine the anti-tumor effect of EEDC in a mouse model of mandibular invasion by gingival squamous cell carcinoma (SCC). METHODS: The rhizome of D crassirhizoma was extracted in ethanol. The anti-invasive effect of EEDC was analyzed with a Matrigel-coated transwell invasion and 3D culture system. Crucial factors related to the control of cancer cell invasion by EEDC were determined using a human protease array. Molecular evidence supporting the anti-invasive effect of EEDC in oral SCC (OSCC) cells used an invadopodia-mediated extracellular matrix (ECM) degradation; an in vivo athymic mouse model was also provided. RESULTS: EEDC treatment (10 µg/mL) suppressed transwell migration and invasion of HSC-3 OSCC cells without cytotoxicity. Decreased levels of matrix metalloprotease (MMP)-7, kalikrein 10, cathepsin V, MMP-2, and cathepsin D were also found in EEDC-treated HSC-3 cells based on human protease array. The anti-invasive effects of EEDC involved the suppression of invadopodia-mediated ECM degradation via inhibition of globular-actin elongation. The anti-invasive effect resulting from disturbance of functional invadopodia formation by EEDC was observed even at a low concentration of 5 µg/mL. The phosphorylation of cortactin involved in functional invadopodia formation was decreased at EEDC concentrations that inhibited invadopodia formation. The anti-tumor effect of EEDC was also observed in a mouse xenograft model. Administration of EEDC resulted in inhibition of tumor growth and progression. CONCLUSIONS: EEDC represents a potential anti-invasive and anti-tumor agent in cancer control.


Actins/metabolism , Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/drug therapy , Dryopteris/chemistry , Neoplasm Invasiveness/prevention & control , Plant Extracts/pharmacology , Polymerization/drug effects , Animals , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Male , Mice , Mice, Inbred BALB C , Phosphorylation/drug effects
7.
BMC Complement Altern Med ; 17(1): 113, 2017 Feb 16.
Article En | MEDLINE | ID: mdl-28202081

BACKGROUND: The fruit of the Terminalia chebula tree has been widely used for the treatment of various disorders. Its anti-diabetic, anti-mutagenic, anti-oxidant, anti-bacterial, anti-fungal, and anti-viral effects have been studied. Dental plaque bacteria (DPB) are intimately associated with gingivitis and periodontitis. In the quest for materials that will prove useful in the treatment and prevention of periodontal disease, we investigated the preventive effects of an ethanol extract of Terminalia chebula (EETC) on DPB-induced inflammation and bone resorption. METHODS: The anti-bacterial effect of EETC was analyzed using the disc diffusion method. The anti-inflammatory effect of EETC was determined by molecular biological analysis of the DPB-mediated culture cells. Prevention of osteoclastic bone resorption by EETC was explored using osteoclast formation and pit formation assays. RESULTS: EETC suppressed the growth of oral bacteria and reduced the induction of inflammatory cytokines and proteases, abolishing the expression of PGE2 and COX-2 and inhibiting matrix damage. By stimulating the DPB-derived lipopolysaccharides, EETC inhibited both osteoclast formation in osteoclast precursors and RANKL expression in osteoblasts, thereby contributing to the prevention of bone resorption. CONCLUSIONS: EETC may be a beneficial supplement to help prevent DPB-mediated periodontal disease.


Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Bacteria/drug effects , Dental Plaque/microbiology , Periodontal Diseases , Plant Extracts/pharmacology , Terminalia , Animals , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Bacteria/growth & development , Bone Resorption/microbiology , Bone Resorption/prevention & control , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Dinoprostone/metabolism , Gingivitis/microbiology , Gingivitis/prevention & control , Inflammation/microbiology , Inflammation/prevention & control , Mice , Mouth/microbiology , Osteoblasts/drug effects , Osteoclasts/drug effects , Peptide Hydrolases/metabolism , Periodontal Diseases/microbiology , Periodontal Diseases/pathology , Periodontal Diseases/prevention & control , Periodontitis/microbiology , Periodontitis/prevention & control , Phytotherapy , Plant Extracts/therapeutic use , RANK Ligand/metabolism , RAW 264.7 Cells
8.
Chem Biol Interact ; 250: 78-84, 2016 Apr 25.
Article En | MEDLINE | ID: mdl-26972667

Melanogenesis is a physiological process that results in the synthesis of melanin pigments, which play a crucial protective role against skin photocarcinogenesis. We investigated the effects of a Polygoni Multiflori Ramulus extract on melanogenesis and isolated emodin from Polygoni Multiflori as an active compound. In addition, the possible mechanisms of action were examined. We found that emodin inhibited both melanin content and tyrosinase activity concentration and time dependently. Tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 mRNA levels decreased following emodin treatment. However, while the mRNA levels of microphthalmia-associated transcription factor (MITF) were not affected by emodin, emodin reduced MITF protein levels. Furthermore, expression of the liver X-receptor (LXR) α gene, but not the LXR ß gene was upregulated by emodin. Moreover, emodin regulated melanogenesis by promoting degradation of the MITF protein by upregulating the LXR α gene. The emodin effects on MITF was found to be mediated by phosphorylation of p42/44 MAPK. Taken together, these findings indicate that the inhibition of melanogenesis by emodin occurs through reduced MITF protein expression, which is mediated by upregulation of the LXR α gene and suggest that emodin may be useful as a hyperpigmentation inhibitor.


Emodin/isolation & purification , Emodin/pharmacology , Fallopia multiflora/chemistry , Melanins/metabolism , Melanocytes/drug effects , Orphan Nuclear Receptors/genetics , Cell Line , Down-Regulation/drug effects , Humans , Liver X Receptors , Melanins/antagonists & inhibitors , Melanocytes/metabolism , Microphthalmia-Associated Transcription Factor/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Orphan Nuclear Receptors/metabolism , Signal Transduction/drug effects , Up-Regulation/drug effects
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