Search Results (314)

Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and dysregulated chemokine signaling. Kaempferia parviflora (KP) has long been valued for its medicinal properties; however, its specific role in psoriasis treatment remains unclear. This study investigates the anti-psoriatic potential of methoxyflavones derived from KP through an integrated approach combining network pharmacology, molecular docking, and experimental validation. A total of 232 target genes were identified as being associated with KP bioactive compounds, of which 64 overlapped with psoriasis-related genes implicated in chemokine signaling pathways. Molecular docking analyses revealed that key methoxyflavones interact with pivotal proteins such as protein kinase B (AKT1 or AKT), proto-oncogene tyrosine-protein kinase (SRC), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), suggesting their potential involvement in modulating inflammation. Experimental results confirmed that 5,7,4′-trimethoxyflavone and 3,5,7-trimethoxyflavone significantly inhibited keratinocyte proliferation, migration, and macrophage activation, key processes in psoriasis progression. Additionally, both compounds reduced nitric oxide production, supporting their anti-inflammatory effects. Western blot analysis further demonstrated that these compounds tended to decrease the phosphorylation levels of AKT and SRC, supporting their role in influencing inflammatory signaling pathways. These findings suggest that methoxyflavones from KP act through multi-target mechanisms, offering potential as natural therapeutic agents for psoriasis. Further, in vivo studies are needed to validate their efficacy and explore their clinical applications. Full article

Psoriasis pathogenesis involves dysregulated immune responses, yet the role of protein prenylation (particularly PGGT1B-mediated geranylgeranylation) in macrophage-driven inflammation remains poorly understood. This study aims to explore the role and molecular mechanism of protein geranylgeranyltransferase type I subunit beta (PGGT1B) in the development of psoriasis. Myeloid cell-specific PGGT1B gene knockout mice were generated, and a mouse psoriasis model was established with imiquimod to study the role and mechanism of PGGT1B gene downregulation-induced macrophage activation in the pathogenesis of psoriasis. Bone marrow-derived macrophages (BMDMs) from wild-type and PGGT1B knockout mice were cultured and stimulated with resiquimod (R848) to simulate the immune microenvironment of psoriasis. In addition, the differentially expressed genes induced by PGGT1B knockout were analyzed using RNA-seq, and bioinformatics analysis was carried out to study the possible biological process of PGGT1B regulation. Finally, PMA-THP-1 was co-cultured with HaCaT cells to study the effect of PGGT1B deletion in macrophages on the proliferation and differentiation of keratinocytes. Bone marrow PGGT1B deficiency aggravated the psoriasis-like lesions induced by imiquimod in mice. In BMDMs with PGGT1B deficiency, the NF-κB signaling pathway was over-activated by R848, and the expressions of proinflammatory cytokines IL-1β, IL-6, and TNF-α were significantly increased. Activation of cell division cycle 42 (CDC42) may mediate the activation of the NF-κB pathway in PGGT1B-deficient BMDMs. PGGT1B deletion can promote the proliferation and inhibit the differentiation of HaCaT cells. Reduced PGGT1B levels can increase the expression of CDC42, which further activates NLRP3 inflammation in macrophages through NF-κB signaling, further aggravating the inflammatory state of psoriasis. Psoriasis-like lesions induced by IMQ are aggravated when PGGT1B expression is reduced in mouse bone marrow cells. A possible mechanism for this is that PGGT1B-deficient macrophages migrate to the epidermis more easily during psoriasis, which leads to the activation of Cdc42, NF-κB signaling, and NLRP3 inflammatory corpuscles. Full article

(1) Background: This study evaluated the potential of an aqueous extract from Quercus robur L. leaves for chronic wound healing. Its composition, rich in bioactive compounds (tannins and flavonoids), confers antioxidant and antimicrobial properties. (2) Methods: The toxicity and ability of the extract to enhance cell migration were tested in human keratinocytes (HaCaT cell line). Additionally, a proteomic analysis was performed on treated cells. (3) Results: The extract exhibited low cytotoxicity (IC50 = 943 µg·mL⁻¹) compared to other plant extracts. At 5 mg·mL⁻¹, it significantly accelerated wound closure at 8 h, surpassing negative control and Reoxcare; however, results were comparable at 12 h. Proteomic analysis identified 117 differentially expressed proteins (21 upregulated, 96 downregulated) involved in essential processes such as cell migration, blood clotting, and cholesterol biosynthesis. Specifically, the extract increased the expression of CYP51A1, LSS, and SQLE, while inhibiting Delta (14)-sterol reductase, key enzymes in cholesterol metabolism, suggesting a potential mechanism for tissue regeneration. (4) Conclusions: The aqueous extract of Q. robur leaves shows promise as a natural therapeutic agent for chronic wound healing, potentially aiding tissue regeneration and modulation of cholesterol metabolism. Full article

Wound healing is a complex, multiphase process crucial for restoring tissue integrity and functionality after injury. Among the emerging therapeutic approaches, antimicrobial peptides (AMPs) have shown substantial promise because of their dual role in microbial defense and cellular modulation. AMP-IBP5, a novel AMP derived from insulin-like growth factor-binding protein 5, exhibits both antimicrobial and wound-healing properties, making it a promising therapeutic candidate. This peptide exhibits robust antimicrobial activity, augments keratinocyte proliferation, increases fibroblast migration, induces angiogenesis, and modulates the immune response. Mechanistically, AMP-IBP5 activates Mas-related G protein-coupled receptors and low-density lipoprotein receptor-related protein 1 (LRP1) in keratinocytes, stimulating IL-8 production and vascular endothelial growth factor expression to accelerate wound healing. This molecule also interacts with LRP1 in fibroblasts to increase cell migration and promote angiogenesis while mitigating inflammatory responses through targeted cytokine modulation. Preclinical studies have demonstrated its remarkable efficacy in promoting tissue repair in diabetic wounds and inflammatory skin conditions, including atopic dermatitis and psoriasis. This review delves into the broad therapeutic potential of AMP-IBP5 across dermatological applications, focusing on its intricate mechanisms of action, comparative advantages, and its path toward clinical and commercial application. Full article

Severe skin damage poses a significant clinical challenge, as limited availability of skin donors, postoperative skin defects, and scarring often impair skin function. Traditional two-dimensional (2D) nanofibers exhibit small pore sizes that hinder cellular infiltration, unable to simulate the three-dimensional (3D) structure of the skin. To address these issues, we developed 3D porous nanofiber scaffolds composed of polycaprolactone–polylactic acid–mussel adhesive protein (PLGA-PCL-MAP) using low-temperature electrospinning combined with nano-spray technology. Meanwhile, this 3D scaffold features high porosity, enhanced water absorption, and improved air permeability. The incorporation of mussel adhesive protein (MAP) further increased the scaffold’s adhesive properties and biocompatibility. In vitro experiments demonstrated that the 3D nanofiber scaffolds significantly promoted the adhesion, proliferation, and migration of epidermal keratinocytes (HaCaTs) and human fibroblasts (HFBs), while providing ample space for inward cellular growth. Successful co-culture of HaCaT and HFBs within the scaffold revealed key functional outcomes: HaCaTs expressed keratinocyte differentiation markers CK10 and CK14, while HFBs actively secreted extracellular matrix components critical for wound healing, including collagen I, collagen III, and fibronectin. This skin substitute with a composite structure of epidermis and dermis based on three-dimensional nanofiber scaffolds can be used as an ideal skin replacement and is expected to be applied in wound repair in the future. Full article

Background/Objectives: Exercise training (ET) can improve wound healing and prevent the recurrence of skin lesions. Aerobic ET stimulates the NAD+-dependent deacetylase sirtuin 1 (SIRT1). The beneficial effects of ET and SIRT1 activation in wound healing have been characterized when considered separately. This study aimed to investigate the potential role of SIRT1 as a mediator of the effects of sera isolated from athletes who regularly participate in aerobic ET (middle-distance running, MDR) on cells primarily involved in wound healing. Methods: Human keratinocytes, fibroblasts and endothelial cells were conditioned with sera from middle-distance runners and age-matched sedentary subjects (sed). Cell motility, angiogenesis and the expression of key biomarkers of cell activation were evaluated in the presence or absence of the selective SIRT1 inhibitor EX-527. Results: Higher SIRT1 activity was detected in all of the cell lines conditioned with the MDR group sera compared with that in the cells in the sed group sera. The involvement of SIRT1 was demonstrated by EX-527’s selective inhibition. Alongside the increase in SIRT1 activity, a marked increase in migration, invasion and angiogenesis was observed. The levels of E-cadherin decreased while those of integrin β1 and vinculin increased in the keratinocytes and fibroblasts conditioned with the MDR group sera compared to these values with the sed group sera, respectively. Increased levels of differentiation markers, such as involucrin in the keratinocytes, FAP1α in the fibroblasts and CD31 in the endothelial cells, were observed with the MDR group sera compared to these values using the sed group sera. Conclusions: The ex vivo/in vitro approach used here links aerobic ET-induced SIRT1 activity to proper tissue regeneration. Full article

Daphne kiusiana is a naturally occurring plant in East Asia belonging to the Thymelaeaceae family. While its biological properties have been explored, its potential role in wound healing remains largely unknown. This study investigated the effects of Daphne kiusiana extracts on keratinocyte migration and the underlying mechanisms. The crude extract and its fractions was tested in vitro at various concentrations to evaluate their ability to promote keratinocyte migration, and a cytotoxicity assay was conducted to assess cell viability. The results demonstrated that Daphne kiusiana significantly enhanced keratinocyte migration without inducing notable cytotoxicity at tested concentrations. Mechanistically, this effect was mediated through the modulation of matrix metalloproteinase-9 (MMP-9) via extracellular signal-regulated kinase (ERK) signaling, which plays a crucial role in keratinocyte migration. These findings suggest that Daphne kiusiana may serve as a potential therapeutic agent for enhancing keratinocyte migration in wound healing. However, further investigations, including clinical studies, are necessary to confirm its efficacy and safety. To our knowledge, this is the first study to report the potential of Daphne kiusiana in promoting keratinocyte migration, offering new insights into wound healing therapies. Full article

Background/Objectives: There is a great demand for novel, multipurpose, natural skin-care products in the global skin repair and sun protection markets. Within this framework, the potential benefits of topical Vitamin D2 (VD2) administration in combination with silver nanoparticles (AgNPs) were examined. Methods: Evaluating the efficacy of the VD2+AgNP cream in wound healing, skin irritation and UVB irradiation protection necessitated preclinical testing using reconstructed human skin equivalent models (prepared from human foreskins) containing both a fully stratified epidermal layer and underlying dermis. Results: Application of the cream significantly improved wound healing by stimulating keratinocyte re-epithelialization and dermal fibroblast migration in models subjected to full-thickness (scratch and biopsy punch) wounds, compared to untreated models. The VD2+AgNP cream, administered prior to the induction of skin irritation by 5% sodium dodecyl sulfate (SDS) afforded protection by ameliorating cell viability epidermal thickness and interleukin-1alpha levels. UVB exposure (50 mJ/cm²) significantly reduced cell viability and epidermal thickness (associated with increased epidermal breakage), as well as basal layer Ki67 and supra-basal layer involucrin expression, compared to the CTRL sham-irradiated models. The cream administered prior to UVB irradiation (protective capacity) showed greater efficacy in minimizing epidermal damage. This was reflected by significantly higher Ki67 and involucrin expression, as well as lower epidermal breakage, compared to models where the cream was applied following UVB irradiation (curative capacity). Conclusions: The VD2+AgNP cream shows multipurpose potential in skin protection. The underlying molecular mechanisms remain to be investigated. Full article

This study aims to highlight the therapeutic potential of some Lamiacea essential oils (EOs). For this purpose, eight EOs, including two from Lavandula angustifolia Mill. cultivated in Romania and Spain (LA1 and LA2), Salvia officinalis L. (SO), Lavandula hybrida Balb. ex Ging (LH), Salvia sclarea L. (SS), Mentha smithiana L. (MS), Perovskia atriplicifolia Benth. (PA), and Mentha x piperita L. (MP), were evaluated in vitro in terms of antioxidant, cytotoxic, antimicrobial, and anti-migratory activities. As regards the antioxidant capacity, expressed as the EO concentration that produces 50% of the maximum effect (IC₅₀ value), the EOs obtained from the cultivated plants of the Lamiaceae family are ordered as follows: LA2 ˃ LA1 ˃ LH > MP > MS > SO > SS > PA. For the determination of antimicrobial activity, the reference strains used for testing were Salmonella enterica serotype typhimurium, Shigella flexneri serotype 2b, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Candida parapsilosis. The most intense inhibitory effect was observed in EOs of MS and MP on all tested microbial strains. The cytotoxic and anti-migratory activity of EOs was tested on two melanoma cell lines (A375 and B164A5) and on a healthy keratinocyte line (HaCaT). EOs LA1 and MP manifested the highest selectivity on the analysed tumoural cells, by reducing their migration in comparison with the control, proving to have therapeutic potential. Full article

The extract of Scenedesmus deserticola JD052 has been reported to exhibit anti-aging effects on the skin, with research indicating an increase in loliolide, a major active component, through heterotrophic cultivation. In this study, we evaluated the effects of extracts obtained from both photoautotrophic (PE) and heterotrophic (HE) cultures on hair-inductive properties in human dermal papilla (HDP) cells. Biochemical assays demonstrated that both extracts enhanced HDP cell viability and increased the size of three-dimensional dermal papilla (DP) spheres. Notably, the activation of β-catenin, a crucial marker associated with hair growth, was assessed using a luciferase reporter assay, revealing that HE exhibited a significantly higher efficacy than PE. Further analyses indicated that HE promoted the translocation of β-catenin into the nucleus through the phosphorylation and activation of AKT, which also elevated the expression levels of DP signature genes and hair-growth-related autocrine factors. Additionally, conditioned media from HE-treated HDP cells enhanced keratinocyte migration and increased the expression of growth factors, including VEGF and IGF-1. HPLC-MS analysis showed no significant difference in loliolide content; however, specific peaks in HE were identified as pheophorbide A and linolelaidic acid. Thus, HE may enhance hair growth inductivity via AKT/β-catenin signaling. Full article

Chronic wounds (CWs) in humans affect millions of people in the US alone, cost billions of dollars, cause much suffering, and still there are no effective treatments. Patients seek medical care when wound chronicity is already established, making it impossible to investigate factors that initiate chronicity. In this study, we used a diabetic mouse model of CWs that mimics many aspects of chronicity in humans. We performed scRNAseq to compare the cell composition and function during the first 72 h post-injury and profiled 102,737 cells into clusters of all major cell types involved in healing. We found two types of fibroblasts. Fib 1 (pro-healing) was enriched in non-CWs (NCWs) whereas Fib 2 (non-healing) was in CWs. Both showed disrupted proliferation and migration, and extracellular matrix (ECM) deposition in CWs. We identified several subtypes of keratinocytes, all of which were more abundant in NCWs, except for Channel-related keratinocytes, and showed altered migration, apoptosis, and response to oxidative stress (OS) in CWs. Vascular and lymphatic endothelial cells were both less abundant in CWs and both had impaired migration affecting the development of endothelial and lymphatic microvessels. Study of immune cells showed that neutrophils and mast cells are less abundant in CWs and that NCWs contained more proinflammatory macrophages (M1) whereas CWs were enriched in anti-inflammatory macrophages (M2). Also, several genes involved in mitochondrial function were abnormally expressed in CWs, suggesting impaired mitochondrial function and/or higher OS. Heat shock proteins needed for response to OS were downregulated in CWs, potentially leading to higher cellular damage. In conclusion, the initiation of chronicity is multifactorial and involves various cell types and cellular functions, indicating that one type of treatment will not fix all problems, unless the root cause is fundamental to the cell and molecular mechanisms of healing. We propose that such a fundamental process is high OS and its association with wound infection/biofilm. Full article

Background/Objectives: C24 ceramide plays a crucial role in skin regeneration and wound healing; however, its hydrophobic nature limits its application in therapeutic formulations. This study aims to enhance the bioavailability and efficacy of C24 ceramide by developing ceramide-based lipid nanoparticles (C24-LNP) and evaluate their impact on skin regeneration and wound healing. Methods: C24-LNP was synthesized and characterized for aqueous stability and bioavailability. In vitro experiments were conducted to assess its effects on keratinocyte proliferation and migration. Molecular biological analysis examined key signaling pathways, including AKT and ERK1/2 phosphorylation. Additionally, an in vivo mouse wound model was utilized to evaluate wound healing efficacy, with histological analysis performed to assess epidermal and dermal regeneration. Results: C24-LNP exhibited improved aqueous stability and bioavailability compared to free C24 ceramide. In vitro studies demonstrated that C24-LNP significantly promoted keratinocyte proliferation and migration. Molecular analysis revealed activation of the AKT and ERK1/2 signaling pathways, which are critical for cell growth and skin regeneration. In vivo wound healing experiments showed that C24-LNP accelerated wound closure compared to the control group. Histological analysis confirmed enhanced epidermal and dermal regeneration, leading to improved structural and functional skin repair. Conclusion: The lipid nanoparticle formulation of C24 ceramide effectively increases its bioavailability and enhances its therapeutic efficacy in skin regeneration and wound healing. C24-LNP presents a scalable and cost-effective alternative to traditional growth factor-based therapies, offering significant potential for clinical applications in wound care and dermatological treatments. Full article

Salvia haenkei (SH-Haenkenium^®), a native plant of Bolivia, is known as strong inhibitor of senescence and recently exploited in wound healing and for its potential anti-inflammatory properties. Hyaluronan at high and low molecular weight (HCC), explored in diverse cell models, and recently used in clinical practice, showed beneficial effects in dermo aesthetic and regenerative injective treatments. In this research work a novel formulation based on HCC coupled SH was tested for its potentiality in counteracting dermal injury. In vitro wound healing has been used to demonstrate HCC + SH capacity to improve keratinocytes migration respects the sole HCC, supported also by positive modulation of remodeling and integrity biomarkers. In addition, an in vitro dehydration test showed its ability to defend the skin from dryness. Moreover, an in vitro inflammation model (with lipopolysaccharides derived from E. coli) was used to assess molecular fingerprint of the pathological model and compare the cell response after treatments. Inflammatory biomarkers (e.g., KRT6, TLR-4 and NF-κB) and specific cytokines (e.g., IL-6, IL-22, IL-23) proved the effect of HCC + SH, in reducing inflammatory mediators. A more complex model, 3D-FT skin, was used to better resemble an in vivo condition, and confirmed the efficacy of novel formulations to counteract inflammation. All results trigger the interest in the novel formulation based on SH extract and hyaluronan complexes for its potential efficacy as natural anti-inflammatory agent for damaged skin, for its healing and regenerative properties. Full article

Background/Objectives: Cashew nutshell liquid (CNSL) is obtained during the industrial processing of cashew nuts. It contains anacardic acid (2-hydroxy-6-n-pentadecylbenzoic acid) and cardanol (3-n-pentadecylphenol). Therefore, CNSL provides a rich source of phenolic lipids serving as natural antioxidants or precursors for industrial uses. Here, we have analyzed in detail a commercial sample of cardanol by nuclear magnetic resonance (NMR) spectroscopy and its biological activities in the human keratinocyte cell line (HaCaT cells). Methods: The cytotoxic effects, genotoxicity, cell proliferation, and healing properties on HaCaT cells were studied using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, comet assay, proliferation assay, and scratch assay, respectively. Additionally, the modulatory effect of cardanol on the cellular fatty acid profile of HaCaT cells was analyzed by gas chromatography. Results: NMR showed the structure of cardanol as a mixture of the 8′-monoene (42%), the 8′,11′-diene (22%), and the 8′,11′,14′-triene (36%) for the pentadecyl side chain with all double bonds in Z configuration. The cytotoxic effects on HaCaT cells only occurred at high concentrations of cardanol (>10 µg/mL), which caused significant reductions in cell viability. Using the comet assay, a dose-dependent increase in DNA damage was found at concentrations above 10 µg/mL. Scratch assays revealed that cardanol achieved 99% wound closure of HaCaT cells treated with 1 µg/mL cardanol after 48 h. Cardanol at 1 and 0.1 µg/mL significantly enhanced HaCaT cell proliferation and promoted migration, contributing to accelerated wound healing processes. As shown by gas chromatography, 1 µg/mL cardanol increased the total amount of polyunsaturated fatty acids (PUFA), including ω-3, ω-6, and ω-9 fatty acids. Conclusions: Together, these findings suggest that concentrations of <10 µg/mL cardanol are safe and exhibit beneficial biological activities, particularly wound-healing effects on HaCaT cells. Further studies are necessary to explore additional potential applications of cardanol, to refine its formulations for clinical use, and to ensure its safety and action in other target cells and species. Full article

To study Cassia alata (CA) (Linnaeus) Roxburgh’s effectiveness towards atopic dermatitis (AD), CA leaf extracts were prepared using three methanol-based extraction solvent systems. Bioactive constituents were characterized and quantified via high-performance liquid chromatography with diode array detection. Antioxidant properties and antimicrobial activities against Staphylococcus aureus, a major AD exacerbation factor, were assessed. Four polyphenols (two flavonoids, two anthraquinones) beneficial in AD control were detected (rhein > aloe-emodin > astragalin > kaempferol). The 75% v/v MeOH/water extract had the most polyphenols and the best antioxidant profile (total phenolic content, total flavonoid content, 2,2-diphenyl-1-picrylhydrazyl-hydrate radical scavenging activity, ascorbic acid equivalent antioxidant capacity), with excellent S. aureus inhibition (minimum inhibitory concentration = 0.625 mg/mL; minimum bactericidal concentration = 1.25 mg/mL). Hence, it was selected for the in vitro examination of cytotoxicity and wound healing activity towards human epidermal keratinocyte cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2h-tetrazolium bromide (MTT) assay and wound scratch assay. The extract showed no cytotoxicity (IC₅₀ > 100 µg/mL) without significant reduction in cell viability up to 200 µg/mL compared to the vehicle control. An amount of 50 μg/mL extract concentration showed the best wound-healing activity (p < 0.05), with a cell migration rate of 5.89 ± 0.80 µm/h over 96 h post-treatment. Such antioxidant, antimicrobial, and wound-healing activities suggest CA and its polyphenols to be promising natural, long-term AD remedies for skin health. Full article