Search Results (73)

Ultraviolet B (UVB) radiation is a major environmental factor contributing to skin photoaging through excessive reactive oxygen species (ROS) generation, activation of stress-responsive signaling pathways, DNA damage, cellular senescence, and extracellular matrix (ECM) degradation. Mangiferin, a naturally occurring xanthone glucoside with potent antioxidant and anti-inflammatory properties, has attracted considerable interest as a potential photoprotective agent. The present study investigated the protective effects of mangiferin against UVB-induced photoaging in human dermal fibroblasts (HDFs). The effects of mangiferin on oxidative stress, RAGE/NF-κB/MAPK signaling, DNA damage, cellular senescence, and ECM degradation were evaluated. Mangiferin significantly suppressed UVB-induced ROS accumulation and attenuated activation of the RAGE/NF-κB/MAPK signaling cascade. Furthermore, mangiferin reduced γ-H2AX expression, indicating protection against UVB-mediated DNA damage, while decreasing p16, p21, and p53 expression and restoring LMNB1 levels. Mangiferin also inhibited MMP-2 and MMP-9 activities as well as collagenase, elastase, and hyaluronidase activities, suggesting preservation of ECM homeostasis. These findings demonstrate that mangiferin protects dermal fibroblasts against UVB-induced photoaging through suppression of oxidative stress, inhibition of RAGE/NF-κB/MAPK signaling, attenuation of DNA damage and cellular senescence, and preservation of ECM integrity, supporting its potential application in photoprotective and anti-photoaging dermocosmetic formulations. Full article

Background: Skin photoaging, primarily induced by chronic ultraviolet (UV) radiation exposure, is characterized by dryness, wrinkle formation, pigmentation abnormalities, and reduced skin elasticity, resulting from oxidative stress, inflammation, and degradation of the extracellular matrix. Codonopsis pilosula, a traditional food–medicine homologous plant, is recognized for its anti-aging properties. However, its lipophilic components (designated as CP-L) remain insufficiently explored. Methods: Herein, we developed a thermosensitive nanogel encapsulating CP-L-loaded transferosomes (CP-L nanogel) to enhance topical delivery and evaluated its effects in both a UV-induced photoaging mouse model and UVB-irradiated HaCaT keratinocytes. Results: In UV-induced mice, topical application of the nanogel markedly reduced skin wrinkling and epidermal hyperplasia, with epidermal thickness decreased by 83.2% compared to the model group (p < 0.01), and restored skin elasticity and collagen deposition, as evidenced by a 35.5% increase in collagen area fraction (p < 0.01). Correspondingly, in UVB-irradiated HaCaT cells, it significantly increased cell viability from 53.0 ± 9.6% to 89.4 ± 1.0% (p < 0.01) and suppressed apoptosis from 30.1 ± 0.48% to 12.4 ± 0.66% (p < 0.01). Furthermore, the CP-L nanogel consistently attenuated oxidative stress, with SOD, CAT, and GSH-Px activities increased by 73.1%, 188.1%, and 18.2%, respectively (p < 0.01), and MDA levels reduced by 71.0% (p < 0.01), while inflammatory responses were suppressed, as TNF-α, IL-1α, IL-1β, and IL-6 levels decreased by 28.3%, 22.6%, 12.8% and 31.9%, respectively (p < 0.01). Mechanistically, transcriptomic and molecular analyses revealed that the nanogel potently inhibited the UV-induced activation of the FGFR/PI3K/AKT/mTOR/p70S6K signaling cascade at both transcriptional and protein levels, with the phosphorylation levels of FGFR, PI3K, AKT, mTOR, and p70S6K significantly reduced by 43.9%, 30.9%, 38.8%, 34.9%, and 57.3%, respectively (p < 0.01). Molecular docking and dynamics simulations identified isofuranodienone and aromadendrene oxide-(2) as key constituents with high-affinity, stable binding to FGFR1 and AKT1. The cytoprotective effect of the nanogel was completely abolished by co-treatment with the FGFR inhibitor PD173074, confirming functional reliance on this pathway. Enhanced cellular delivery of the formulation was directly demonstrated by flow cytometry, showing an approximately 1.8-fold increase in cellular uptake compared to the free drug (p < 0.01). Conclusions: Collectively, these results demonstrated that the CP-L nanogel alleviated skin photoaging through a multi-faceted mechanism involving enhanced cellular delivery, potent antioxidant and anti-inflammatory activities, and specific inhibition of the FGFR/PI3K/AKT/mTOR signaling cascade, highlighting its potential as a multitargeted topical agent derived from an edible plant. Full article

Exposure to ultraviolet (UV), particularly UVA radiation, is a primary driver of photoaging due to its deep dermal penetration, which triggers DNA damage, collagen degradation, and immune suppression. Chebulinic acid (CA), a polyphenolic compound from Terminalia chebula, exhibits potent antioxidant and anti-inflammatory properties against UVB-induced skin damage. However, its large molecular weight hinders transdermal delivery and the TAT_47–57 peptide (core of HIV-1 TAT) enables rapid transmembrane transport. Large particles with double-layer membrane structure and a diameter exceeding 1000 nm were obtained during the separation of plant-derived exosome-like nanoparticles (PELNs), which are not considered as PELNs (50–500 nm), after a mixture with TAT anchored to the surface of engineered artificial vesicles (EAVs) and extrusion causes membrane fusion, employed as novel nanocarriers to overcome the difficulty in skin penetration by leveraging their lipid bilayer structure and surface membrane-anchored TAT for efficient epidermal fusion and intercellular penetration. Furthermore, CA-loaded TAT-ePELNs demonstrate significant efficacy in mitigating UVA-induced photoaging. Collectively, this study expands the anti-UVR damage application spectrum of CA from UVB to UVA exposure and establishes a green, efficient, and biosafe strategy for transdermal drug delivery by utilization of non-PELNs generated during the preparation process of PELNs. Full article

Chronic ultraviolet B (UVB) radiation drives cutaneous photoaging—clinically manifesting as erythema, edema, scaling, deep wrinkling, loss of elasticity, and barrier disruption—through mitochondrial reactive oxygen species (mtROS) overproduction and quality-control failure. Here we identify α-ketoglutarate (AKG; also known as 2-oxoglutarate), a TCA-cycle intermediate and essential co-substrate for α-ketoglutarate-dependent dioxygenases (α-KGDDs), as a metabolic corrector of mitochondrial redox homeostasis in UVB-induced photoaging. In a 10-week chronic UVB SKH1 hairless mouse model, microneedle-assisted transdermal delivery of AKG dose-dependently attenuated macroscopic erythema, scaling, and erosive lesions, restored skin barrier function and dermal elasticity, preserved epidermal–dermal architecture, and protected collagen and elastic fiber integrity, with efficacy comparable to all-trans retinoic acid. Mechanistically, AKG reactivated α-KGDD/prolyl hydroxylase (PHD) catalytic function and promoted proteasomal clearance of aberrantly stabilized HIF-1α under normoxia; this was accompanied by restored AMPK Thr172 phosphorylation downstream of constitutive LKB1 and recovery of PGC-1α-driven mitochondrial biogenesis. AKG preferentially attenuated mitochondrial superoxide over total cellular ROS through a co-substrate-mediated mechanism distinct from direct radical scavenging, and its protective effects were largely abrogated by DMOG (an α-KGDD inhibitor) or compound C (an AMPK inhibitor). These findings position AKG, delivered via microneedle-assisted topical application, as a candidate metabolite-based intervention targeting the α-KGDD/HIF-1α/AMPK axis for photoaging. Full article

Ultraviolet B (UVB) radiation-induced corneal injury poses a significant public health challenge. However, its underlying molecular mechanisms remain incompletely understood, hindering the development of effective interventions. This study identified a key molecular pathway in UVB-induced corneal damage, revealing that UVB exposure triggers a rapid intracellular burst of reactive oxygen species (ROS), which in turn upregulates and aberrantly activates the receptor tyrosine kinase Ephrin type-A receptor 2 (EphA2), thereby collectively accelerating DNA damage and photoaging in corneal epithelial cells. Based on this mechanism, we developed the natural compound Penicophenone F (PP-F), which was screened and identified from the Arctic fungus Penicillium sp. MYA5, as a novel therapeutic strategy against UVB-induced corneal damage. In vitro and in vivo experiments suggest that PP-F may mediate its therapeutic effects via a dual mechanism. On one hand, it may counteract UVB damage by modulating ROS levels through regulation of endogenous antioxidant enzymes, inhibiting aberrant EphA2 activation, and promoting cellular proliferation and DNA repair. On the other hand, it may upregulate IRF6 to activate the cGAS pathway, which could enhance antioxidant defenses and significantly contribute to the restoration of epithelial barrier integrity and overall corneal physiology. These results underscore the safety and potential of PP-F in treating UVB-induced corneal damage and other oxidative stress-related ocular surface diseases. Full article

Ultraviolet B (UVB), as a major component of solar radiation, is a key factor in inducing skin photoaging. The epidermis serves as the primary defensive barrier of the skin and absorbs the majority of UVB. This study aims to elucidate the protective effect of Alk against UVB-induced photoaging and further uncover its underlying molecular mechanisms. In vitro, Alk-pretreated HaCaT cells were exposed to UVB. Cell viability, ROS, senescence, antioxidant enzymes, and protein expression were analyzed. Mechanisms were examined using CETSA, DARTS, Co-IP, and NRF2 knockout. In vivo, Alk hydrogel was tested in UVB-exposed BALB/c mice, with protection assessed via histology and immunohistochemistry. In vitro, Alk directly binds to Keap1, disrupts Keap1–Nrf2 interaction, promotes nuclear translocation of Nrf2, and upregulates the expression of its downstream target HO-1. Consequently, intracellular ROS generation is reduced, cellular senescence is alleviated, and the expression of inflammatory factors (TNF-$\alpha$, COX-2) and MMP-9 is suppressed. In vivo, topical application of the Alk hydrogel prevented UVB-induced skin thickening and collagen degradation. Alk exerts a preventive effect on UVB-induced photoaging in HaCaT cells and skin, providing strong support for developing Alk as a potential plant-derived active ingredient for preventing skin photoaging. Full article

Ultraviolet (UV) radiation from the sun causes adverse skin changes such as premature aging. UV-induced mitochondrial DNA (mtDNA) alterations, including deletions, contribute to photoaging and cellular dysfunction. While the most frequent mtDNA rearrangement is the common deletion (CD), characterized by the loss of nearly one-third of the genome (4977 bp), detailed knowledge of mechanisms governing UV-mediated initiation of the CD and mitigation strategies are lacking. Here, we investigated how increasing UV exposure increases CD levels in human skin fibroblasts via cellular reactive oxygen species (ROS) formation and mtDNA oxidation and demonstrated that antioxidant preconditioning of cells prevents UVA-induced CD accumulation. Conversely, UVB exposure induced cyclobutane pyrimidine dimers (CPDs) without affecting ROS, suggesting an ROS-independent pathway. Using a 3D full-thickness human skin model, we confirmed UVA-dependent CD formation in both the epidermis and dermis. RNA-Seq analysis of UVA-exposed fibroblasts revealed upregulation of mitochondrial DNA replication genes and downregulation of mtDNA repair genes. These findings provide insight into how UVA and UVB differ in detrimental effects on mtDNA, with UVA impacting mtDNA maintenance and transcription via a ROS-dependent mechanism, and provide a physiologically relevant platform to evaluate potential interventions. Full article

Ultraviolet (UV) radiation is a primary driver of skin photoaging, characterized by oxidative stress, persistent inflammatory responses, and excessive degradation of the extracellular matrix (ECM). Naematelia aurantialba is a traditional medicinal and edible fungus recognized for its diverse pharmacological activities. In this study, N. aurantialba polysaccharides (NAPS-A)—high-value bioactive compounds obtained through liquid fermentation—were subjected to detailed functional characterization to evaluate their restorative potential against UVB-induced damage. The results demonstrated that NAPS-A treatment effectively mitigated UVB-induced cytotoxicity. Furthermore, NAPS-A significantly suppressed the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), while robustly revitalizing the endogenous antioxidant defense system by restoring superoxide dismutase (SOD) and catalase (CAT) activities. Moreover, NAPS-A exerted potent anti-inflammatory effects by inhibiting the secretion of nitric oxide (NO) and pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. NAPS-A maintained ECM homeostasis by counteracting collagen depletion, exhibiting inhibitory activity against collagenase and elastase, and modulating the mRNA expression of Col1a1 and Col3a1. These findings suggested that NAPS-A protects fibroblasts from UVB-induced damage through a synergistic mechanism involving radical scavenging, the enhancement of cellular redox homeostasis, and the modulation of ECM metabolism. Overall, NAPS-A represents a promising, sustainably produced, food-derived bioactive ingredient with significant potential for the development of functional foods and nutricosmetics aimed at mitigating UVB-induced skin damage. Full article

Prolonged exposure to ultraviolet (UV) radiation in sunlight is a major extrinsic factor that impairs skin function and accelerates photoaging. In this study, a murine model of ultraviolet B (UVB)-induced photoaging exhibited characteristic symptoms, including skin roughness, erythema, hyperpigmentation, and increased wrinkle formation. Epicatechin gallate (ECG), a natural flavonoid, has demonstrated potential skin-protective properties. However, its specific effects and mechanisms against UVB-induced photoaging are not fully understood. Here, we investigated the protective role and underlying mechanism of ECG against UVB-induced damage in human epidermal keratinocytes (HaCaT cells). Using network pharmacology, p38 mitogen-activated protein kinase (p38 MAPK), specifically the p38α isoform, was identified as a key potential target of ECG. Our experimental results confirmed that ECG significantly attenuated UVB-induced photoaging. Mechanistically, ECG treatment effectively suppressed UVB-triggered phosphorylation of p38α, promoted autophagic flux (as evidenced by increased LC3B conversion and decreased p62 levels), and substantially reduced intracellular reactive oxygen species (ROS) accumulation. Consequently, ECG mitigated mitochondrial dysfunction, restored normal cell cycle progression, and decreased the expression of senescence-associated markers (p53, p16, p21) and inflammatory cytokines (IL6, TNF-α). In summary, our findings demonstrate that ECG protects against UVB-induced photoaging primarily by inhibiting p38α activation, thereby enhancing autophagy and alleviating oxidative stress. This study positions ECG as a promising therapeutic candidate for preventing and treating skin photoaging. Full article

Ultraviolet B (UV-B) radiation significantly contributes to skin photoaging, which is characterized by epidermal thickening, collagen degradation, wrinkle formation, barrier dysfunction, and oxidative stress. Nicotinamide mononucleotide (NMN), a key precursor of nicotinamide adenine dinucleotide, regulates cellular energy metabolism and antioxidant defense and demonstrates anti-aging effects in animal models. Here, we investigated the protective effects of oral NMN supplementation against UV-B-induced photoaging in SKH-1 hairless mice. Over a 10-week experimental period, oral NMN administration significantly alleviated epidermal hypertrophy, reduced wrinkle formation and skin surface roughness, improved hydration and elasticity, and restored transepidermal water loss to near-normal levels. Histological analyses revealed marked preservation of collagen fiber density and attenuation of dermal matrix degradation. Furthermore, NMN supplementation inhibited the phosphorylation of MAPK signaling components (ERK, JNK, and p38), suppressed pro-inflammatory cytokine (TNF-α and IL-6) and matrix-degrading enzyme (MMP-1) expression, and restored hyaluronan synthase (HAS-1 and HAS-2) expression. Additionally, NMN enhanced the systemic antioxidant defense, as indicated by the restored superoxide dismutase activity. Thus, NMN has multi-layered protective effects against UV-B–induced skin aging by modulating oxidative stress, inflammatory signaling, extracellular matrix remodeling, and hyaluronic acid metabolism. Full article

Ultraviolet radiation B (UVB) radiation can induce oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, impaired barrier function, and an increased risk of cancer. Addressing or preventing photoaging may provide a promising therapeutic avenue for these conditions. Hyperoside (HY), a compound abundantly found in medicinal plants including Hypericum perforatum and Crataegus, has been reported to have various pharmacological activities such as antioxidant, anti-inflammatory, cytoprotective, and antitumor effects; however, there are currently no studies systematically exploring the potential and mechanisms of HY in alleviating skin damage caused by ultraviolet (UV) rays. We investigated the inhibitory effects of HY on oxidative stress responses, reducing keratinocyte aging. HY can also exert these effects by mediating the PI3K/AKT/mTOR signaling pathway through miR-361-5p, maintaining mitochondrial dynamic stability, alleviating mitochondrial dysfunction, and enhancing mitophagy. Additionally, in vivo, HY was able to significantly improve skin wrinkles in mice while reducing changes in thickness and aging of the epidermis and dermis. Full article

Background: Ultraviolet B (UVB) radiation induces oxidative stress, inflammation, and collagen degradation in skin, leading to photodamage. Ergosterol (ERG)—a sterol widely distributed in fungi and algae, including numerous marine species—possesses antioxidant and anti-inflammatory activities, but its photoprotective mechanisms remain unclear. Methods: Using integrated in vitro (UVB-irradiated human keratinocytes) and in vivo (topical ERG in a murine UVB model) approaches, combined with transcriptomic and network pharmacology analyses, we evaluated ERG’s effects on oxidative stress, inflammation, and extracellular matrix integrity. Results: ERG treatment preserved keratinocyte viability, reduced reactive oxygen species, and suppressed pro-inflammatory mediators after UVB exposure. In mice, topical ERG significantly attenuated epidermal hyperplasia, maintained tight-junction integrity, and inhibited collagen matrix degradation. Mechanistically, ERG exerted dual inhibition of the nuclear factor kappa B (NF-κB) pathway, which mediates inflammation, and the mitogen-activated protein kinase (MAPK) pathway, which regulates collagen degradation. Conclusions: These findings identify ERG as a marine-derived sterol with potent photoprotective activity that simultaneously targets oxidative stress, inflammation, and extracellular matrix damage, highlighting its promise as a natural compound for dermatological applications and aligning with ongoing efforts to explore marine-derived agents against skin oxidative stress and inflammation. Full article

Skin aging, including photoaging, is primarily triggered by chronic exposure to solar radiation, which induces free radical formation, cellular deoxyribonucleic acid (DNA) damage, and structural skin alterations. Achillea millefolium L. (Asteraceae) is rich in phenolic compounds and alkamides, substances known for their antioxidant activity. This study aimed to develop and characterize a photoprotective phytocosmetic nanoemulsion containing crude root extract of A. millefolium. The extract exhibited a total phenolic content of 3.067 ± 1.911 µg GAE/mL, potent antioxidant activity (EC₅₀ = 69.11 ± 8.899 µg/mL), moderate tyrosinase inhibition (19 ± 1.8%), and no cytotoxicity in keratinocytes. The extract was incorporated into nanoemulsions at concentrations of 0.1%, 0.5%, and 1%. The resulting droplets showed mean diameters of 217 to 230 nm, with a significant increase in the polydispersity index (PDI) after extract addition (p < 0.05). Transmission electron microscopy (TEM) confirmed the spherical morphology of the droplets. The in vitro sun protection factor (SPF) was 14 ± 0.9 in the control formulation and increased to 15 ± 2.0 (0.1%), 22 ± 5.2 (0.5%), and 17 ± 1.0 (1%), suggesting a synergistic effect between the extract and chemical filters. All formulations demonstrated UVA/UVB ratio > 0.6, a pH near to 5, occlusive properties, and good spreadability. The results indicate that A. millefolium extract holds potential for safe photoprotective formulations, offering a valuable antioxidant and depigmenting activity in addition to enhancing the SPF. This position is an innovative alternative to phytocosmetic development. Full article

Background: Ultraviolet B (UVB) radiation accelerates skin aging by inducing oxidative stress, collagen degradation, and cellular senescence. Although Petasites japonicus is known for its antioxidant properties, its anti-photoaging potential remains underexplored. This research explored the protective properties of a hot water extract from P. japonicus leaves (KP-1) against photoaging caused by UVB exposure. Methods: Hairless mice were exposed to UVB three times per week and orally administered KP-1 for 13 weeks. Wrinkle formation, epidermal thickness, skin hydration, and collagen content were assessed. Protein expression related to MAPK/AP-1, TGF-β/Smad2/3, and p53/p21 pathways was analyzed by Western blotting. Results: KP-1 significantly reduced UVB-induced wrinkle area, epidermal and dermal thickening, and transepidermal water loss while restoring collagen density and skin hydration. KP-1 inhibited MMP-1 expression, enhanced COL1A1 levels, suppressed MAPK/AP-1 activation, and activated TGF-β/Smad2/3 signaling. It also balanced p53/p21 expression and restored cyclin D1 and CDK4 levels, thereby preventing UVB-induced senescence. Conclusions: The findings of this research revealed that KP-1 can serve as a promising natural substance for safeguarding the skin from damage and aging caused by UVB exposure. Full article

Sunlight contains a wide spectrum of radiation from ultraviolet (UV) through visible light to infrared (IR). UV radiation plays a crucial role in skin damage, photoaging, and carcinogenesis, necessitating effective photoprotection strategies. The study evaluated the efficacy of protective lipsticks with different sun protection factor (SPF) values (10, 15, and 30) against UVA and infrared (IR) radiation. In this study, the directional-hemispherical reflectance (DHR) was measured across various spectral bands (335–380 nm, 400–540 nm, 700–1100 nm, and 1000–1700 nm) with SOC 410 Reflectometer (San Diego, CA, USA). Since the device used in this study did not cover the UVB range (290–320 nm), this study does not provide a direct assessment of SPF in its conventional sense. The measurements were taken at four time points up to 120 min after lipstick application. Results indicated that lipsticks with higher SPF values significantly altered skin reflectance in UVA and IR ranges, with SPF30 showing the lowest reflectance in the UVA range (335–380 nm), suggesting greater absorption of UVA radiation by the product and significantly higher reflectance in IR ranges compared to lower SPF lipsticks. Reflectance values generally increased over time post-application for key spectral bands. These findings demonstrate that SPF lipsticks provide variable attenuation of UVA and IR radiation, highlighting their role in comprehensive lip photoprotection. The data support the importance of SPF selection for optimized protection, especially against penetrating UVA and IR components of sunlight. Full article