Comprehensive Analysis of Exosomal MicroRNAs Derived from UVB-Irradiated Keratinocytes as Potential Melanogenesis Regulators.

The exosomes derived from keratinocytes can have a substantial impact on melanogenesis by influencing melanocytes. MicroRNAs (miRNAs) encapsulated within exosomes are implicated in the control of melanogenesis, particularly when under the influence of UVB irradiation. This investigation explores UVB-induced exosomal miRNAs from keratinocytes as potential regulators of melanogenesis. UVB-irradiated, keratinocyte-derived exosomes were observed to augment melanogenesis in melanocytes, resulting in an upregulation of MITF, TRP1, TRP2, and TYR expression compared to non-UVB-irradiated exosomes. Additionally, a subset of exosomal miRNAs was differentially selected and confirmed to exert both enhancing and inhibitory effects on melanogenesis through functional assays. Notably, hsa-miR-644a, hsa-miR-365b-5p, and hsa-miR-29c-3p were found to upregulate melanogenesis, while hsa-miR-18a-5p, hsa-miR-197-5p, and hsa-miR-4281 downregulated melanogenesis. These findings suggest the involvement of keratinocyte-derived exosomal miRNAs in melanogenesis regulation within melanocytes. The expression levels of exosomal miRNAs from keratinocytes exhibited a UVB-dependent increase, indicating a potential role for these miRNAs as regulators of melanogenesis in response to UVB irradiation. Furthermore, melanogenesis was found to be dependent on exosomes derived from keratinocytes. This underscores the potential of UVB-induced exosomal miRNAs derived from keratinocytes as regulators of melanogenesis. Moreover, this study unveils a significant role for exosomes in melanocyte pigmentation, presenting a novel pathway in the intricate process of melanogenesis.

Phosphorylation of glucocorticoid receptor induced by 16-kauren-2-beta-18, 19-triol decreases expression of Melanophilin through JNK signalling.

16-kauren-2-beta-18, 19-triol (16-kauren) is a natural diterpenoid substance derived from Asteraceae psiadia punctulata, a small tropical shrub in Africa and Asia, and it can reduce Mlph expression without affecting the expression of Rab27a and MyoVa in melanocytes. Melanophilin (Mlph) is an important linker protein in the melanosome transport process. However, the signal transduction pathway for the regulation of Mlph expression has not been fully established. We examined the mechanism of 16-kauren on Mlph expression. Murine melan-a melanocytes were used for in vitro analysis. Western blot analysis, quantitative real-time polymerase chain reaction, and luciferase assay were performed. The inhibition of Mlph expression by 16-kauren-2ß-18,19-triol (16-kauren) occurs through the JNK signal and is reversed following glucocorticoid receptor (GR) activation by dexamethasone (Dex). Especially, 16-kauren activates JNK and c-jun signalling, part of the MAPK pathway, with subsequent Mlph repression. When the JNK signal is weakened by siRNA, the inhibition of Mlph expression by 16-kauren was not seen. JNK activation by 16-kauren induces GR phosphorylation, which leads to Mlph repression. These results demonstrate that 16-kauren regulates Mlph expression through the phosphorylation of GR via the JNK signalling pathway.

The Effect of Lactobacillus plantarum Extracellular Vesicles from Korean Women in Their 20s on Skin Aging.

Extracellular vesicles, which are highly conserved in most cells, contain biologically active substances. The vesicles and substances interact with cells and impact physiological mechanisms. The skin is the most external organ and is in direct contact with the external environment. Photoaging and skin damage are caused by extrinsic factors. The formation of wrinkles is a major indicator of skin aging and is caused by a decrease in collagen and hyaluronic acid. MMP-1 expression is also increased. Due to accruing damage, skin aging reduces the ability of the skin barrier, thereby lowering the skin's ability to contain water and increasing the amount of water loss. L. plantarum suppresses various harmful bacteria by secreting an antimicrobial substance. L. plantarum is also found in the skin, and research on the interactions between the bacteria and the skin is in progress. Although several studies have investigated L. plantarum, there are only a limited number of studies on extracellular vesicles (EV) derived from L. plantarum, especially in relation to skin aging. Herein, we isolated EVs that were secreted from L. plantarum of women in their 20s (LpEVs). We then investigated the effect of LpEVs on skin aging in CCD986sk. We showed that LpEVs modulated the mRNA expression of ECM related genes in vitro. Furthermore, LpEVs suppressed wrinkle formation and pigmentation in clinical trials. These results demonstrated that LpEVs have a great effect on skin aging by regulating ECM related genes. In addition, our study offers important evidence on the depigmentation effect of LpEVs.

Three New Isoprenylated Flavones from Artocarpus chama Stem and Their Bioactivities.

Phytochemical investigation of Artocarpus chama stem was performed by chromatographic techniques, resulting from the isolation and structure elucidation of three new compounds, namely 3'-farnesyl-apigenin (1), 3-(hydroxyprenyl) isoetin (2), and 3-prenyl-5,7,2',5'-tetrahydroxy-4'-methoxyflavone (3), and five known compounds, namely homoeriodictyol (4), isocycloartobilo-xanthone (5), artocarpanone (6), naringenin (7), and artocarpin (8). From the screening result, A. chama extract showed a potent tyrosinase inhibitory effect. Ihe isolated compounds 1, 4 and 6 also exhibited tyrosinase inhibition with IC50 of 135.70, 52.18, and 38.78 µg/mL, respectively. Moreover, compounds 3, 4, 5, 6, and 8 showed strong activity against Staphylococcus epidermidis, S. aureus, methicillin-resistant S. aureus, and Cutibacterium acnes. This study is the first report on phytochemical investigation with new compounds and biological activities of A. chama. Skin infection can cause dark spots or hyperpigmentation. The isolated compounds that showed both anityrosinase and antimicrobial activities will be further studied in in vivo and clinical trials in order to develop treatment for hyperpigmentation, which is caused by infectious diseases by microorganisms.

Antiaging Potential of Fucoxanthin Concentrate Derived from Phaeodactylum tricornutum.

The aim of the study was to investigate the potential of a fucoxanthin concentrate prepared from Phaeodactylum tricornutum as a wrinkle care cosmetic agent. The concentrate (up to 25 µg/ml) did not affect the proliferation of human fibroblasts. In addition, the concentrate significantly increased procollagen synthesis in the fibroblasts at 12.5 and 25 µg/ml; however, it significantly decreased the expression of matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 at 25 µg/ml. In a follow-up study, a wrinkle care cream containing 0.03% of fucoxanthin concentrate was prepared and tested in women (aged 35-50 years, n = 21) for 8 weeks. The cream was applied twice daily. Safety assessment of the cream was carried out visually. In addition, interviews were conducted to investigate if adverse events such as erythema, edema, scaling, itching, stinging, burning, tightness, or prickling had occurred. No symptoms that threaten skin safety were reported. Evaluation of wrinkles around the eyes using the replica method showed a statistically significant decrease in wrinkles at week 8. Moreover, skin moisture and elasticity increased significantly from week 4. These results suggest that the fucoxanthin concentrate has no adverse effects on the skin and can be used as an active ingredient in wrinkle care cosmetics.

The absence of Rab27a accelerates the degradation of Melanophilin.

Melanophilin (Mlph) forms an interaction with Rab27a and the actin-based motor protein MyosinVa (MyoVa) on mature melanosome membranes and the tripartite complex regulates melanosome transport in melanocytes. In this study, we found that Rab27a siRNA decreased Mlph and Rab27a protein levels, but Mlph mRNA levels were not changed. Other Rab27a siRNA sequences also showed the same results. When Rab27a siRNA was treated with melan-a melanocytes, Rab27a protein was decreased within 6 hours and Mlph protein was decreased within 24 hours. To determine whether the absence of Rab27a promotes Mlph degradation, we inhibited protein degradation by treatment with proteasome (MG132) and lysosomal enzyme (E64D and Pepstatin A) inhibitors in melan-a melanocytes. MG132 inhibited the degradation of Mlph, but E64D and Pepstatin A had no effect on Mlph. The absence of Rab27a enhanced ubiquitination of Mlph and induced proteasomal degradation. From these results, we concluded that Mlph interaction with Rab27a is important for Mlph stability and melanosome transport.

In vivo Change of Keratin-Bound Molecules in the Human Stratum Corneum following Exposure to Ultraviolet Radiation.

BACKGROUND/OBJECTIVES: Ultraviolet (UV) radiation damages the stratum corneum (SC) and disrupts the skin barrier. The damaged skin changes in the molecular composition of the SC, including its water content. However, it is difficult to examine the in vivo SC changes with existing methods, so those have not been well characterized. Therefore, we investigated in vivo changes of UV-induced SC damage using confocal Raman spectroscopy. METHOD: We irradiated the volar forearm of 10 subjects with 0.5, 1, and 1.5 minimal erythemal doses of UV radiation. Then, we examined erythema, the transepidermal water loss (TEWL), the water content, the natural moisturizing factor (NMF), and the lipids of the skin. RESULTS: After UV irradiation, erythema and TEWL of the skin were both increased. The bound water content of the SC was also increased following UV irradiation. The NMF of the SC revealed different tendencies. All free amino acids (FAAs) of the NMF were increased after UV irradiation, except proline. trans-urocanic acid, pyrrolidone carboxylic acid, lactate, and urea, which are NMF components produced by the subsequent catabolism of FAAs and sweat, were decreased after UV irradiation. The amount of ceramide in the SC was also decreased after UV exposure, while cholesterol was increased. CONCLUSIONS: The bound water content of the SC was increased by UV exposure along with increasing TEWL, several NMF components, and cholesterol. These in vivo results for UV-damaged SC obtained via Raman spectroscopy could be applied to research with regard to protecting the SC from UV radiation and treating UV-damaged SC.

Dehydroabietic Acid Induces Regeneration of Collagen Fibers in Ultraviolet B-Irradiated Human Dermal Fibroblasts and Skin Equivalents.

BACKGROUND/AIMS: Dehydroabietic acid (DAA) is a natural phytochemical found in red pine trees and herbal plants. While DAA and its derivatives are known for improving diabetes and hyperlipidemia, the antiaging effect and its underlying mechanisms of DAA on skin have not been fully examined. Here, we assessed the antiaging effects of DAA on human dermal fibroblasts and skin equivalents. METHODS: We investigated the effect of DAA on the secretion of type I procollagen and matrix metalloproteinase-1 (MMP-1) in ultraviolet B (UVB)-irradiated neonatal normal human dermal fibroblasts (NHDFn). Using nonlinear optical imaging techniques, we visualized quantitative and qualitative changes of collagen fibers by DAA treatment in human skin equivalent models. RESULTS: DAA induces increases in type I procollagen secretion when treated on UVB-irradiated NHDFn. DAA also downregulates secretion of MMP-1 through the inhibition of the JNK signaling pathway. In human skin equivalent models, we successfully visualized the spatial distribution of collagen fibers in the dermis and found that quantity, diameter, and arrangement of collagen fibers in the dermis were significantly improved by DAA treatment. CONCLUSION: Our results suggest that DAA could be a useful agent for improving skin photoaging through the protection and regeneration of collagen fibers in skin.

Manifestation of atopic dermatitis-like skin in TNCB-induced NC/Nga mice is ameliorated by topical treatment of substance P, possibly through blockade of allergic inflammation.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus and eczematous lesion. In this study, topically applied substance P (SP) significantly alleviated AD-like clinical symptoms in 2, 4, 6-trinitrochlorobenzene (TNCB)-induced dermatitis in NC/Nga mice. This effect was nullified by pretreatment of the neurokinin-1 receptor (NK-1R) antagonist CP99994. SP treatment significantly reduced the infiltration of mast cells and CD3-positive T cells as well as inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and thymic stromal lymphopoietin (TSLP), in AD-like skin lesions and decreased the levels of IgE and thymus and activation-regulated chemokine in serum. This SP-induced alleviation of allergic inflammatory responses was also confirmed as reduced activation in the axillary lymph nodes (aLN) and spleen, suggesting the systemic effect of SP on immune responses in TNCB-induced NC/Nga mice. Furthermore, SP-mediated TSLP reduction was confirmed in human keratinocyte culture under pro-inflammatory TNF-α stimulation. Taken together, these results suggest that topically administered SP may have potential as a medication for atopic dermatitis.

Cell-Penetrating Peptide-Patchy Deformable Polymeric Nanovehicles with Enhanced Cellular Uptake and Transdermal Delivery.

We herein propose a polymeric nanovehicle system that has the ability to remarkably improve cellular uptake and transdermal delivery. Cell-penetrating peptide-patchy deformable polymeric nanovehicles were fabricated by tailored coassembly of amphiphilic poly(ethylene oxide)- block-poly(ε-caprolactone) (PEO- b-PCL), mannosylerythritol lipid (MEL), and YGRKKRRQRRR-cysteamine (TAT)-linked MEL. Using X-ray diffraction, differential scanning calorimetry, and nuclear magnetic resonance analyses, we revealed that the incorporation of MEL having an asymmetric alkyl chain configuration was responsible for the deformable phase property of the vehicles. We also discovered that the nanovehicles were mutually attracted, exhibiting a gel-like fluid characteristic due to the dipole-dipole interaction between the hydroxyl group of MEL and the methoxy group of PEO- b-PCL. Coassembly of TAT-linked MEL with the deformable nanovehicles significantly enhanced cellular uptake due to macropinocytosis and caveolae-/lipid raft-mediated endocytosis. Furthermore, the in vivo skin penetration test revealed that our TAT-patchy deformable nanovehicles remarkably improved transdermal delivery efficiency.

Structurally Stable Attractive Nanoscale Emulsions with Dipole-Dipole Interaction-Driven Interdrop Percolation.

This study introduces an extremely stable attractive nanoscale emulsion fluid, in which the amphiphilic block copolymer, poly(ethylene oxide)-block-poly(ϵ-caprolactone) (PEO-b-PCL), is tightly packed with lecithin, thereby forming a mechanically robust thin-film at the oil-water interface. The molecular association of PEO-b-PCL with lecithin is critical for formation of a tighter and denser molecular assembly at the interface, which is systematically confirmed by T2 relaxation and DSC analyses. Moreover, suspension rheology studies also reflect the interdroplet attractions over a wide volume fraction range of the dispersed oil phase; this results in a percolated network of stable drops that exhibit no signs of coalescence or phase separation. This unique rheological behavior is attributed to the dipolar interaction between the phosphorylcholine groups of lecithin and the methoxy end groups of PEO-b-PCL. Finally, the nanoemulsion system significantly enhances transdermal delivery efficiency due to its favorable attraction to the skin, as well as high diffusivity of the nanoscale emulsion drops.

A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent.

BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B) agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2) and microphthalmia-associated transcription factor (MITF) in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA) and cAMP response element-binding protein (CREB) activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders.

Modulation of melanin synthesis by rengyolone isolated from the root of Eurya emarginata in melan-a cells.

In the course of screening for the melanogenesis inhibitors, rengyolone was isolated from Eurya emarginata (Thumb) Makino. Its chemical structure was determined on the basis of spectroscopic analysis including mass spectroscopy and nuclear magnetic resonance analysis. Rengyolone inhibited potent melanogenesis in melan-a cells with an IC50 value of 65 µM without cytotoxicity. Also, rengyolone showed a melanin biosynthesis inhibition zone in a culture plate of Streptomyces bikiniensis, which is commonly used as an indicator organism. Moreover, rengyolone dramatically reduced protein expression of melanogenic enzyme, tyrosinase. Furthermore, rengyolone presented inhibition on the body pigmentation in zebrafish model system and decreased melanin contents and tyrosinase activity. These results suggest that rengyolone isolated from E. emarginata may be an effective skin-whitening agent that regulates the expression of melanogenic enzymes.

BMP-2 regulates the expression of myosin Va via smad in melan-a melanocyte.

Myosin Va (Myo Va) is one of three protein complexes involved in melanosome transport. In this study, we identified BMP-2 as an up-regulator of Myo Va expression using 2-methyl-naphtho[1,2,3-de]quinolin-8-one (MNQO). Our results showed that MNQO reduced the mRNA and protein expression of Myo Va and BMP-2 in melanocytes. Knockdown of BMP-2 by siRNA also affected Myo Va mRNA and protein expression, confirming that MNQO regulates Myo Va through BMP-2. Furthermore, phosphorylation of Smad1/5/8 by BMP2 treatment confirmed that the BMP-2/Smad signaling pathway regulates Myo Va expression in Melan-a melanocytes. Smad-binding elements were found in the Myo Va promoter and phosphorylated Smad1/5/8 bind directly to the Myo Va promoter to activate Myo Va transcription and BMP-2 enhances this binding. These findings provide insight into a new role for BMP-2 in Melan-a melanocytes and a mechanism of regulation of Myo Va expression that may be beneficial in the treatment of albinism or hyperpigmentation disorders.

Upcycled canola meal extract mitigates UVB-induced skin wrinkling by regulating photoaging-related biomarkers in hairless mice.

Canola meal, a by-product of processing canola into oil, reportedly contains high amounts of phenolic compounds and proteins. However, as canola meal is primarily used as feed for livestock, advances in multiple research fields are required to broaden its potential applications. Photoaging is caused by continuous exposure to ultraviolet (UV) radiation from sunlight. UV radiation generates reactive oxygen species and destroys collagen in the skin, thickening the epidermis, reducing elasticity, and causing wrinkles. We hypothesized that canola meal extract (CME) can mitigate the damage to skin associated with wrinkles induced by exposure to UVB radiation. To evaluate the anti-wrinkle effect, we administered CME orally to 40 female Hos:HR-1 hairless mice divided into 5 groups: (1) control mice, (2) a UVB group, and (3-5) CME-treated groups (CME-250, 500, and 1000 mg/kg body weight/day, respectively). All groups except the controls were irradiated with UVB 3 times a week to create wrinkles due to photoaging. CME administration inhibited the increase of the number, mean length, and mean depth of wrinkles induced by UVB radiation as assessed using a skin replica. Histopathological image analysis revealed that CME administration resulted in a decrease in epidermal thickness and an increase in collagen content, while increasing catalase activity and hydroxyproline content in skin tissues. CME administration inhibited the phosphorylation of mitogen-activated protein kinase and decreased the production of collagenase and gelatinase. These results suggest that CME, an upcycled material, has the potential to develop into a healthful and functional food ingredient with anti-wrinkling effects.

Dissection of SNARE-driven membrane fusion and neuroexocytosis by wedging small hydrophobic molecules into the SNARE zipper.

Neuronal SNARE proteins mediate neurotransmitter release at the synapse by facilitating the fusion of vesicles to the presynaptic plasma membrane. Cognate v-SNAREs and t-SNAREs from the vesicle and the plasma membrane, respectively, zip up and bring about the apposition of two membranes attached at the C-terminal ends. Here, we demonstrate that SNARE zippering can be modulated in the midways by wedging with small hydrophobic molecules. Myricetin, which intercalated into the hydrophobic inner core near the middle of the SNARE complex, stopped SNARE zippering in motion and accumulated the trans-complex, where the N-terminal region of v-SNARE VAMP2 is in the coiled coil with the frayed C-terminal region. Delphinidin and cyanidin inhibited N-terminal nucleation of SNARE zippering. Neuronal SNARE complex in PC12 cells showed the same pattern of vulnerability to small hydrophobic molecules. We propose that the half-zipped trans-SNARE complex is a crucial intermediate waiting for a calcium trigger that leads to fusion pore opening.

Chemical Constituents from Streblus taxoides Wood with Their Antibacterial and Antityrosinase Activities Plus in Silico Study.

Hyperpigmentation frequently occurs after inflammation from bacterial infection. Thus, the inhibition activity of tyrosinase, the key enzyme to catalyze the melanogenesis and/or inhibition of bacterial infection, could decrease melanin production. Hence, the potential inhibitors could be discovered from natural products. ω-Hydroxymoracin C (1), a new compound with two other 2-arylbenzofurans, i.e., moracin M (2) and moracin C (3), and two stilbenes, i.e., 3, 4, 3', 5'-tetrahydroxybibenzyl (4) and piceatannol (5), were isolated from the wood of Streblus taxoides. Compound 4 showed a strong inhibitory activity against tyrosinase enzyme with an IC50 value of 35.65 µg/mL, followed by compound 2 with an IC50 value of 47.34 µg/mL. Conversely, compound 1, 3 and 5 showed moderate activity, with IC50 values of 109.64, 128.67 and 149.73 µg/mL, respectively. Moreover, compound 1 and 3 showed an antibacterial effect against some Staphylococcus spp. Thus, the isolated compounds exhibited potential antityrosine and antibacterial effects. Additionally, an in silico study was performed in order to predict theoretical molecular interactions between the obtained metabolites from S. taxoides and tyrosinase as an extended in vitro enzyme binding assay experiment.

Comparison of structural characteristics and molecular markers of rabbit skin, pig skin, and reconstructed human epidermis for an ex vivo human skin model.

The Organization for Economic Co-operation and Development approved a reconstructed human epidermis (RHE) model for in vitro skin irritation and corrosion tests as an alternative to animal testing for cosmetics, which has been banned in the European Union since 2013. However, RHE models have several limitations, such as high manufacturing costs, a loose skin barrier, and inability to simulate all cellular and non-cellular components of the human epidermis. Therefore, new alternative skin models are needed. Ex vivo skin models have been suggested as promising tools. Here, we investigated the structural similarities in the epidermis of pig and rabbit skin, a commercial RHE model (Keraskin), and human skin. To compare the structural similarity, the thickness of each epidermal layer was compared using molecular markers. Among the candidate human skin surrogates, the epidermal thickness of the pig skin was the most similar to that of human skin, followed by rabbit skin and Keraskin. Keraskin showed thicker cornified and granular layers than human skin, while rabbit skin displayed thinner layers. Moreover, the proliferation indices of Keraskin and rabbit skin were higher than those of human skin, whereas the proliferation index of the pig skin was similar to that of human skin. Some or none of the human skin barrier proteins FLG, CLDN1, and CDH1 were expressed in pig and rabbit skin, whereas all human proteins were expressed in Keraskin. Collectively, we propose ex vivo pig skin as the most suitable model for skin irritation testing because of its similarity to human skin. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00185-1.

Enhancing spatial resolution in Fourier transform infrared spectral image via machine learning algorithms.

Owing to the intrinsic signal noise in the characterization of chemical structures through Fourier transform infrared (FT-IR) spectroscopy, the determination of the signal-to-noise ratio (SNR) depends on the level of the concentration of the chemical structures. In situations characterized by limited concentrations of chemical structures, the traditional approach involves mitigating the resulting low SNR by superimposing repetitive measurements. In this study, we achieved comparable high-quality results to data scanned 64 times and superimposed by employing machine learning algorithms such as the principal component analysis and non-negative matrix factorization, which perform the dimensionality reduction, on FT-IR spectral image data that was only scanned once. Furthermore, the spatial resolution of the mapping images correlated to each chemical structure was enhanced by applying both the machine learning algorithms and the Gaussian fitting simultaneously. Significantly, our investigation demonstrated that the spatial resolution of the mapping images acquired through relative intensity is further improved by employing dimensionality reduction techniques. Collectively, our findings imply that by optimizing research data through noise reduction enhancing spatial resolution using the machine learning algorithms, research processes can be more efficient, for instance by reducing redundant physical measurements.

The Effect of γ-Aminobutyric Acid Intake on UVB- Induced Skin Damage in Hairless Mice.

The skin, the largest organ in the body, undergoes age-related changes influenced by both intrinsic and extrinsic factors. The primary external factor is photoaging which causes hyperpigmentation, uneven skin surface, deep wrinkles, and markedly enlarged capillaries. In the human dermis, it decreases fibroblast function, resulting in a lack of collagen structure and also decreases keratinocyte function, which compromises the strength of the protective barrier. In this study, we found that treatment with γ-aminobutyric acid (GABA) had no toxicity to skin fibroblasts and GABA enhanced their migration ability, which can accelerate skin wound healing. UVB radiation was found to significantly induce the production of matrix metalloproteinase 1 (MMP-1), but treatment with GABA resulted in the inhibition of MMP-1 production. We also investigated the enhancement of filaggrin and aquaporin 3 in keratinocytes after treatment with GABA, showing that GABA can effectively improve skin moisturization. In vivo experiments showed that oral administration of GABA significantly improved skin wrinkles and epidermal thickness. After the intake of GABA, there was a significant decrease observed in the increase of skin thickness measured by calipers and erythema. Additionally, the decrease in skin moisture and elasticity in hairless mice exposed to UVB radiation was also significantly restored. Overall, this study demonstrates the potential of GABA as functional food material for improving skin aging and moisturizing.