Search Results (3,114)

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder affecting 10–20% of the population. In this study, we investigate the anti-inflammatory effect on the skin of eight compounds isolated from Digitalis purpurea L., using tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-stimulated human keratinocytes (HaCaT cells) and a three-dimensional (3D) reconstructed human skin model. Among the tested compounds, desrhamnosyl acteoside exhibited the most potent activity, significantly reducing the secretion of pro-inflammatory cytokines (IL-6, IL-8) and chemokines (CCL17, CCL22), suppressing the expression of inflammatory proteins, and modulating key signaling pathways, including NF-κB, JAK2/STAT1, and MAPK. Notably, this is the first report demonstrating that desrhamnosyl acteoside simultaneously targets all three pathways, indicating a multi-modal mechanism distinct from conventional single-target approaches. In the 3D skin model, desrhamnosyl acteoside further exhibited barrier-protective effects by downregulating inflammatory mediators and upregulating epidermal differentiation markers such as involucrin and loricrin. These findings reveal a previously uncharacterized phytochemical with dual anti-inflammatory and barrier-restorative activities, supporting its potential as a novel therapeutic candidate for AD and other inflammatory skin diseases. Full article

With the growing interest in natural strategies for preventing skin aging, plant-derived compounds are being actively investigated for their potential protective effects against skin inflammation and extracellular matrix (ECM) degradation. In this study, we explored the anti-aging and anti-inflammatory effects of harringtonine, an alkaloid isolated from Cephalotaxus harringtonia, in normal human epidermal keratinocytes (NHEKs) under inflammatory stress induced by tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Harringtonine significantly suppressed the expression of matrix metalloproteinases (MMP)-1, MMP-2, and MMP-9 and restored the expression of collagen synthesis-related genes [collagen type I alpha 1 chain (COL1A1), collagen type I alpha 2 chain (COL1A2), and collagen type IV alpha 1 Chain COL4A1)], indicating its protective role in ECM degradation. Additionally, harringtonine improved the expression of skin barrier-related genes, such as serine peptidase inhibitor kazal type 5 (SPINK5), loricrin (LOR), quaporin-3 (AQP3), filaggrin (FLG), and keratin 1 (KRT1) although it had no significant effect on involucrin (IVL). Harringtonine also markedly reduced the production of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and IL-8] and inflammatory mediators, including prostaglandin E₂ (PGE₂), cyclooxygenase-2 (COX-2), and nitric oxide (NO). Our findings suggest that harringtonine may serve as a promising natural compound for mitigating skin aging and inflammation through multi-targeted modulation of ECM remodeling, skin barrier function, and inflammatory response. Full article

This study aimed to evaluate the protective effects of Inula japonica leaf extract against PM₁₀-induced oxidative stress in normal human keratinocytes. Keratinocytes were pretreated with various concentrations of Inula japonica leaf extract and subsequently exposed to PM10. Cell viability, ROS production, gene and protein expression (qRT-PCR and Western blot), and UHPLC-MS profiling were assessed. Network pharmacology analysis was conducted using database-predicted compounds of Inulae Flos. The extract significantly reduced PM₁₀-induced ROS generation and restored the expression of epidermal barrier-related genes such as loricrin. It also inhibited phosphorylation of MAPKs (ERK, p38) and modulated apoptotic and inflammatory markers including Bax, p53, MMP-9, and COX-2. UHPLC-MS analysis identified eight compounds not previously reported in our earlier study, which may contribute to the extract’s protective effects. Inula japonica leaf extract exerts protective effects against PM₁₀-induced skin damage by reducing oxidative stress and inflammation in keratinocytes. These findings support its potential as a therapeutic candidate for pollution-related skin disorders. Full article

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory dermatosis of the pilosebaceous unit characterized by nodules, abscesses, and dermal tunnels. Recent transcriptomic studies have implicated dysregulation of innate and adaptive immune responses, epidermal barrier dysfunction, and systemic metabolic alterations. This review synthesizes findings from 16 studies investigating the HS transcriptome using bulk and single-cell RNA sequencing. Differential gene expression analyses revealed extensive upregulation of inflammatory cytokines and chemokines, particularly in lesional and perilesional skin. These changes were also mirrored in non-lesional skin, suggesting diffuse immune dysregulation beyond visibly affected areas. Downregulated pathways include those involved in lipid metabolism, muscle contraction, and neuronal signaling, potentially linking HS to obesity, metabolic syndrome, and neuropsychiatric comorbidities. Single-cell transcriptomics confirmed the enrichment of keratinocytes and immune cells (B cells, plasma cells, M1 macrophages, and T cells) with proinflammatory profiles in HS lesions. Keratinocyte dysfunction further implicated a compromised epidermal barrier in disease pathogenesis. While transcriptomic studies have advanced mechanistic understanding and highlighted therapeutic targets—such as the IL-1β–TH17 axis and B cell signaling pathways—methodological heterogeneity limits cross-study comparisons. Integration of multi-omics data and standardized phenotyping will be essential to identify robust biomarkers, stratify HS subtypes, and guide personalized therapeutic approaches. Full article

Wild edible plants, historically valued for their medicinal properties, can be a sustainable source of food, cosmetics, and pharmaceuticals. The blue berries of Prunus spinosa L., known as blackthorns, have antioxidant, astringent, and antimicrobial benefits. To preserve these properties after harvesting, understanding the best storage methods is essential. In this study, blackthorns were preserved using different methods (air-drying, freezing, or freeze-drying) to determine the optimal procedure for preserving their antioxidant activity. The fruits were extracted using a 50:50 (V/V) mixture of ethanol and water. The different extracts were phytochemically characterized for their phenolic content and antioxidant activity. The Folin–Ciocalteu test revealed total phenolic contents of 7.97 ± 0.04, 13.99 ± 0.04, and 7.39 ± 0.08 (mg GAE/g raw material) for the three types of extracts, respectively. The total flavonoid contents were 2.42 ± 0.16, 3.14 ± 0.15, and 2.32 ± 0.03 (mg QE/g raw material), respectively. In line with the polyphenol analysis, the antioxidant activity as determined by DPPH method was higher for the frozen extract, with a value of 91.78 ± 0.80%, which was confirmed by the ROS test on keratinocytes. These results show that both air-drying and freeze-drying processes negatively impact the preservation of antioxidant activity in blackthorns, suggesting that freezing may be the best preservation method before bioactive compound extraction. Full article

Background/Objectives: Periodontitis is a chronic infectious inflammatory disorder that affects the supporting structures of the teeth. The gingival epithelium plays a crucial role as a physical and immunological barrier, producing pro-inflammatory cytokines in response to microbial pathogens. Modulation of gingival epithelial function has been proposed as a therapeutic strategy to prevent the progression of periodontal disease. Houttuynia cordata, a perennial herb traditionally used in Asian medicine, is recognized for its anti-inflammatory properties, with documented benefits in the cardiovascular, respiratory, and gastrointestinal systems. However, its potential therapeutic role in oral pathologies, such as periodontitis, remains underexplored. This study aimed to investigate the anti-inflammatory effects of H. cordata extract on interleukin (IL)-1β-stimulated primary gingival keratinocytes (PGKs) subjected to IL-1β-induced inflammatory stress, simulating the conditions encountered during orthodontic treatment. Methods: Inflammation was induced in PGKs using IL-1β, and the impact of H. cordata extract pretreatment was assessed using quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblotting. Results: H. cordata extract significantly downregulated the mRNA and protein expression levels of tumor necrosis factor-alpha, IL-8, and intercellular adhesion molecule-1 in IL-1β-stimulated PGKs without inducing cytotoxicity. Conclusions: These findings suggest that H. cordata holds promise as a preventive agent against periodontitis by attenuating inflammatory responses in gingival epithelial tissues. We believe that our findings will inform the development of prophylactic interventions to reduce periodontitis risk in patients undergoing orthodontic therapy. Full article

Background/Objectives: The increasing incidence rates of keratinocyte carcinoma (KC), particularly in fair-skinned populations, call for efforts to intensify health education of the general population in addressing this prevalent skin cancer type. As a preparatory step, this systematic review summarizes the published research on the knowledge and risk perception regarding KC among individuals without medical training. Methods: The review was registered in PROSPERO (CRD42024618851) and adheres to PRISMA guidelines. The databases PubMed, Scopus, Web of Science, PsycArticles, and PsycINFO were searched on 30 July 2024. Studies were eligible if knowledge and/or risk perception was assessed in lay people. Risk of bias (ROB) was assessed with the Joanna Briggs Institute checklist for prevalence studies. Comparable outcomes (e.g., awareness of terms for KC) were meta-analyzed. Results: Included reports (n = 17) were published between 1991 and 2024 with 16,728 individuals assessed. Awareness for the most common type of KC, basal cell carcinoma (BCC), was low (20.75% of respondents (95% confidence interval (CI): 15.24–27.61)), while more respondents were familiar with colloquial terms (60.9–72.8%). Meta-analysis indicated an underestimation of the frequency of KC, with only 7.21% (CI: 4.03–12.58) identifying BCC as the most common type of skin cancer. Furthermore, concern about developing KC as assessed in only two overlapping studies was reported by only 25–30% of respondents, indicating a significant gap in risk awareness and a lack of research on risk perception regarding KC. Conclusions: This review highlights the need for targeted health education interventions to improve knowledge and preventive behaviors regarding KC. Given the limitations of the included studies, characterized by high ROB, heterogeneity of results, and a lack of standardized assessment tools, further research is essential to enhance the understanding and awareness of KC in diverse populations. Full article

Bassia scoparia (Syn. Kochia scoparia (L.) Schrad.) is a medicinal plant whose fruit, Kochiae Fructus, has been extensively studied for its dermatological applications. This study focused on extracts from the whole plant B. scoparia (WPBS), excluding fruits, to address the research gap regarding the medicinal properties of non-fruit parts. The diverse skin benefits of WPBS, including its anti-photoaging, moisturizing, wound healing, anti-inflammatory, and anti-angiogenic effects, were investigated. The WPBS extract enhanced the viability of keratinocytes (HaCaT) without inducing cytotoxic effects. WPBS significantly reduced matrix metalloproteinase-1 (MMP-1) levels and increased collagen type I alpha 1 (COL1A1) levels (p < 0.01) in fibroblasts exposed to ultraviolet B (UVB) radiation, indicating strong anti-photoaging effects. WPBS upregulated skin hydration markers such as aquaporin-3 (AQP3) and hyaluronan synthase-3 (HAS3) and effectively accelerated fibroblast wound closure compared to the positive control. Furthermore, WPBS substantially downregulated the expression of inflammatory (COX-2 and IL-1β) and angiogenic markers (VEGF). Transcriptome analysis (RNA-seq) confirmed that WPBS suppressed inflammation-related and UV-induced gene expression pathways. Overall, these findings expand the therapeutic scope of B. scoparia beyond its traditional fruit use and suggest that WPBS is a promising botanical ingredient for various skin applications. Full article

The high incidence of melanoma leading to a poor prognosis rate endorses the development of alternative and innovative approaches in the treatment of melanoma. Therefore, the present study aims to develop and characterize, in terms of physicochemical features and biological impact, an aqueous suspension of magnetite (Fe₃O₄) coated with β-cyclodextrin (Fe₃O₄@β-CD) as a potential innovative alternative nanosystem for melanoma therapy. The nanosystem exhibited physicochemical characteristics suitable for biological applications, revealing a successful complexation of Fe₃O₄ NPs with β-CD and an average size of 18.1 ± 2.1 nm. In addition, the in vitro evaluations revealed that the newly developed nanosystem presented high biocompatibility on a human keratinocyte (HaCaT) monolayer and selective antiproliferative activity on amelanotic human melanoma (A375) cells, inducing early apoptosis features when concentrations of 10, 15, and 20 μg/mL were employed for 48 h and 72 h. Collectively, the Fe₃O₄@β-CD nanosystem reveals promising features for an adjuvant approach in melanoma treatment, mainly due to its β-cyclodextrin coating, thus endorsing a potential co-loading of therapeutic drugs. Furthermore, the intrinsic magnetic core of Fe₃O₄ NPs supports the magnetically based cancer treatment strategies. Full article

Skin dullness contributes to a fatigued and aged appearance, often exceeding one’s biological age. It is a common dermatological concern influenced by aging and poor lifestyle habits, regardless of ethnicity or age. This study aimed to examine advanced glycation end products (AGEs) and their receptor (receptor for AGEs [RAGE]) as contributing factors to skin dullness. AGEs themselves have a yellowish hue, contributing to “yellow dullness.” Additionally, AGE–RAGE signaling promotes melanin production in melanocytes and impairs keratinocyte differentiation as a result of inflammation. Therefore, regulating the AGE–RAGE interaction may help reduce skin dullness. Through screening various natural ingredients, we found that peony root extract (PRE) inhibits AGE formation and blocks AGE–RAGE binding. Furthermore, the presence of PRE leads to the suppression of AGE-induced melanin production in melanocytes and the restoration of impaired keratinocyte differentiation in glycated basement membrane components. In a human clinical study, topical application of a 1% PRE-containing lotion for 2 weeks significantly reduced melanin content, with a trend toward decreased AGE accumulation and visible spots on the cheeks. These findings support the potential of PRE as a multifunctional cosmetic ingredient that comprehensively addresses skin dullness by modulating the AGE–RAGE interaction. Full article

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Background: Blue light (BL) irradiation has been shown to induce photobiomodulation (PBM) in cells. Here, we investigate its influence on cell types involved in wound healing. Methods: Cellular responses of immortalized human keratinocytes (HaCaTs), normal human dermal fibroblasts (NHDFs), and human umbilical vein endothelial cells (HUVECs) after light treatment at 450 nm were analyzed by kinetic assays on cell viability, proliferation, ATP quantification, migration assay, and apoptosis assay. Gene expression was evaluated by transcriptome analysis. Results: A biphasic effect was observed on HaCaTs, NHDFs, and HUVECs. Low-fluence (4.5 J/cm²) irradiation stimulated cell viability, proliferation, and migration. mRNA sequencing indicated involvement of transforming growth factor beta (TGF-β), ErbB, and vascular endothelial growth factor (VEGF) pathways. High-fluence (18 J/cm²) irradiation inhibited these cellular activities by downregulating DNA replication, the cell cycle, and mismatch repair pathways. Conclusions: HaCaTs, NHDFs, and HUVECs exhibited a dose-dependent pattern after BL irradiation. These findings broaden the view of PBM following BL irradiation of these three cell types, thereby promoting their potential application in wound healing and angiogenesis. Our data on low-fluence BL at 450 nm indicates clinical potential for a novel modality in wound therapy. Full article

Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic^® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm² of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC₅₀ for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article

Wound healing is a complex and dynamic process involving several stages of tissue repair. This study has shown that extracellular vesicles (EVs) derived from the callus of Camellia japonica L. and their associated microRNAs (miRNAs) possess significant wound healing activities. In human fibroblasts, EVs from C. japonica L. stimulated wound healing and upregulated collagen gene expression. The EVs also decreased inflammation levels in human keratinocytes, supporting wound healing. Among the miRNAs identified, miR408, one of the abundant miRNAs in the EVs, also showed similar wound healing efficacy. These findings suggest that both EVs and miR408 from the callus of C. japonica L. play a pivotal role in promoting wound healing. Additionally, this study shows that the regulation of miRNAs between different kingdoms can be achieved and suggests a new direction for the utilization of plant-derived components. Full article

The Kindlin family of scaffold proteins plays key roles in integrin-mediated processes. Kindlin-1 and -2, encoded by the FERMT1 and FERMT2 genes, respectively, are expressed in the epidermis. Kindlin-1 plays protective roles against the development of cutaneous squamous cell carcinomas (cSCCs) in epidermal keratinocytes. However, the role of Kindlin-2 in transformed epidermal keratinocytes has remained virtually unexplored. In this study, we used siRNA approaches to generate Kindlin-2-depleted cells in three isogenic transformed keratinocyte lines. PM1, MET1, and MET4 cells model, respectively, a precancerous lesion, a primary cSCC, and a metastatic lesion of the latter. MET1 cells express both Kindlin-1 and -2. However, Kindlin-1 was not detectable in PM1 and MET4 cells. FERMT2 silencing in PM1 and MET4, but not in MET1 cells, reduced proliferation and the ability to adhere to culture surfaces and spreading. Furthermore, Kindlin-2-depleted PM1 and MET4, but not MET1 cells, exhibited decreased numbers of focal adhesions, as well as an altered F-actin and microtubule cytoskeletal organization. Significantly, FERMT2 silencing reduced the directional migration in all three cell types. These findings are consistent with the concept that, in the absence of other Kindlin orthologues, Kindlin-2 plays a prominent role in the modulation of the proliferation, spreading, focal adhesion assembly, and motility of transformed keratinocytes, as exemplified by PM1 and MET4 cells. Full article