Accelerates Skin Wound Healing Research Articles

Therapeutic effect of ZnO NPs–polyhexanide-hydrogel on Staphylococcus aureus-induced skin wound infection in mice

Nanometer zinc oxide (ZnONPs) offers strong antibacterial, wound healing, hemostatic benefits, and UV protection. Additionally, poly(hexamethylene biguanide)hydrochloride (PHMB) is an environmentally friendly polymer with strong bactericidal properties. However, the synergistic effect of the combination of ZnONPs and PHMB has not been previously explored. The purpose of this study is to explore the synergies of ZnONPs and PHMB and the healing efficacy of ZnO NPs–PHMB-hydrogel on skin wounds in mice infected with Staphylococcus aureus. Therefore, the mice were subjected to skin trauma to create a wound model and were subsequently infected with S. aureus, and then divided into various experimental groups. The repair effect was evaluated by assessing the healing rate, as well as measuring the levels of TNF-α, IL-2, EGF, and TGF-β1 contents in the tissue. On the 4th and 9th days post-modeling, the Z-P group exhibited notably higher healing rates compared to the control group. However, on the 15th day, both the Z-P and AC groups achieved healing rates exceeding 99%. ZnO NPs–PHMB-hydrogel promoted the formation of a fully restored epithelium, increased new hair follicles and sebaceous glands beneath the epidermis, and markedly reduced inflammatory cell infiltration, which was markedly distinct from the control group. On the 7th day, the Z-P group exhibited significantly higher levels of EGF and TGF-β1, along with a considerable reduction in the TNF-α levels as compared with the control group. These results affirmed that ZnO NPs–PHMB-hydrogel effectively inhibits S. aureus infection and accelerates skin wound healing.

Hydrogen sulfide regulates macrophage polarization and necroptosis to accelerate diabetic skin wound healing

Hydrogen sulfide (H2S), recognized as the third gasotransmitter, plays a pivotal role in the pathophysiological processes of various diseases. Cystathionine γ-lyase (CSE) is the main enzyme for H2S production in the skin. However, effects and mechanisms of H2S in diabetic skin wound healing remain unclear. Our findings revealed a decrease in plasma H2S content in diabetic patients with skin wounds. CSE knockout (KO) diabetic mice resulted in delayed wound healing, reduced blood perfusion, and CD31 expression around the wounds. It also led to increased infiltration of inflammatory cells and M1-type macrophages, decreased collagen levels, α-smooth muscle actin (α-SMA), and proliferating cell nuclear antigen (PCNA) expression. Additionally, there were enhanced expressions of necroptosis related proteins, including receptor interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain like protein (MLKL). In comparison, sodium hydrosulfide (NaHS), H2S donor, accelerated skin wound healing in leptin receptor deficiency (db/db) mice. This acceleration was accompanied by increased blood perfusion and CD31 expression, reduced infiltration of inflammatory cells and M1-type macrophages, elevated collagen levels, α-SMA, and PCNA expressions, and decreased necroptosis-related protein expressions together with nuclear factor-κB (NF-κB) p65 phosphorylation. In conclusion, H2S regulates macrophage polarization and necroptosis, contributing to the acceleration of diabetic skin wound healing. These findings offer a novel strategy for the treatment of diabetic skin wounds.

PH-Responsive Calcium Ions and Crocetin Releasing Hydrogel for Accelerating Skin Wound Healing.

The ideal and highly anticipated dressing for skin wounds should provide a moist environment, possess antibacterial properties, and ensure sustained drug release. In the present work, a hyaluronic acid-based hydrogel was formed by cross-linking crocetin and CaCO3@polyelectrolyte materials (CaCO3@PEM) microspheres with HA hydrogels via hydrogen bond and amido bonding (CaCO3@PEM@Cro@HA hydrogel, CPC@HA hydrogel). Moreover, the CPC@HA hydrogel had the capability of sustained, controlled release of calcium ions and crocetin via pH-sensitive and accelerated skin wound healing. The experiment results showed that the CPC@HA hydrogel exhibited porous network structures, stable physical properties, and had antibacterial properties and biocompatibility in vitro. In addition, the CPC@HA hydrogel covering on the skin wound could reduce inflammation and promote wound healing. The high expression of angiogenic cytokines (CD31) and epidermal terminal differentiation markers (Loricrin) of wound healing tissue suggested the CPC@HA hydrogel also had the function of promoting the remodeling of regenerated skin. Overall, CPC@HA hydrogel has promising potential for clinical applications in accelerating skin wound repair.

Functional diversity of apoptotic vesicle subpopulations from bone marrow mesenchymal stem cells in tissue regeneration.

Apoptosis releases numerous apoptotic vesicles that regulate processes such as cell proliferation, immunity, and tissue regeneration and repair. Now, it has also emerged as an attractive candidate for biotherapeutics. However, apoptotic vesicles encompass a diverse range of subtypes, and it remains unclear which specific subtypes play a pivotal role. In this study, we successfully isolated different apoptotic vesicle subtypes based on their sizes and characterized them using NTA and TEM techniques, respectively. We compared the functional variances among the distinct subtypes of apoptotic vesicles in terms of stem cell proliferation, migration, and differentiation, as well as for endothelial cell and macrophage function, effectively identifying subtypes that exhibit discernible functional differences. ApoSEV (with diameter<1000nm) promoted stem cell proliferation, migration, and multi-potent differentiation, and accelerated skin wound healing of diabetes mouse model, while apoBD (with diameter>1000nm) played the opposite effect on cell function and tissue regeneration. Lastly, employing protein analysis and gene sequencing techniques, we elucidated the intrinsic mechanisms underlying these differences between different subtypes of apoEVs. Collectively, this study identified that apoptotic vesicle subtypes possessed distinct bio-functions in regulating stem cell function and behaviour and modulating tissue regeneration, which primarily attribute to the distinct profiling of protein and mRNA in different subtypes. This comprehensive analysis of specific subtypes of apoEVs would provide novel insights for potential therapeutic applications in cell biology and tissue regeneration.

A Thermosensitive Hydrogel with Efficient NIR Photothermal Conversion as Injectable Wound Dressing for Accelerating Skin Wound Healing

AbstractBacterial infection at wound sites can easily induce robust inflammation. M1 macrophages at wound sites can cause cascade inflammatory reactions to mediate a vicious inflammation cycle. Meanwhile, the hypoxia situation further aggravates the destruction and contraction of blood vessels in the wound microenvironment, therefore, hindering the infected wound healing process. Here, a thermosensitive hydrogel is reported to solve the above challenges by eliminating bacteria based on the photothermal effect, regulating the inflammatory immune microenvironment, and providing oxygen (O2). In vitro and in vivo experiments confirmed that the hydrogel has great O2‐producing properties. Based on the excellent photothermal properties of AIEgens, the hydrogel has a good bactericidal effect against S. aureus (100%) and E. coli (98.85%). The RNA‐sequencing revealed that Cur@AIE@MnO2/gel can interfere with the metabolic process and genetic material repair process to impact bacteria proliferation and biofilm dispersal, thus achieving excellent anti‐bacterial efficacy. Moreover, Cur@AIE@MnO2/gel can also up‐regulate anti‐inflammatory genes, down‐regulate pro‐inflammatory genes in macrophages, and facilitate the promotion of macrophage polarization from M1 to M2 to relieve inflammation. The therapeutic experiments show that this hydrogel accelerated the wound‐healing process. Therefore, this work may open new avenues for the development of novel dressings for bacterial‐infected wounds.

Human Parathyroid Hormone (1–34) accelerates skin wound healing through inducing cell migration via up-regulating the expression of Rac1

Delayed wound healing is a public issue that imposes a significant burden on both society and the patients themselves. To date, although numerous methods have been developed to accelerate the speed of wound closure, the therapeutic effects are partially limited due to the complex procedures, high costs, potential side effects, and ethical concerns. While some studies have reported that the in-vivo application of Human Parathyroid Hormone (1–34) (hPTH(1–34)) promotes the wound-healing process, the definitive role and underlying mechanisms through which it regulates the behavior of fibroblasts and keratinocytes remains unclear. Herein, hPTH(1–34)’s role in cell migration is evaluated with a series of in-vitro and in-vivo studies, whereby hPTH(1–34)’s underlying mechanism in activating the two types of cells was detected. The in-vitro study revealed that hPTH(1–34) enhanced the migration of both fibroblasts and HaCaT cells. Ras-associated C3 botulinum toxin subunit 1 (Rac1), a classical member of the Rho family, was upregulated in hPTH(1–34)-treated fibroblasts and HaCaT cells. Further study by silencing the expression of Rac1 with siRNA reversed the hPTH(1–34)-enhanced cell migration, thus confirming that Rac1 was involved in hPTH(1–34)-induced cell behavior. In-vivo study on rat wound models confirmed the effects of hPTH(1–34) on fibroblasts and keratinocytes, with increased collagen deposition, fibroblasts accumulation, and Rac1 expression in the hPTH(1–34)-treated wounds. In summary, the present study demonstrated that hPTH(1–34) accelerated wound healing through enhancing the migration of cells through the up-regulation of Rac1 expression.

Chitosan Hydrogel Dressing Loaded with Adipose Mesenchymal Stem Cell-Derived Exosomes Promotes Skin Full-Thickness Wound Repair.

Cutaneous trauma repair is still a challenge in the clinic due to the scar formation and slow healing rate, especially for diabetic patients. Various drug-loading wound dressings have been explored to solve this problem. Mesenchymal stem cell (MSC)-derived exosomes have been considered as a potential cell-free drug because of their anti-inflammation function and tissue repair property that are comparable to that of MSCs. Herein, a composite wound dressing (Exo/Gel) consisting of the chitosan hydrogel and adipose MSC-derived exosome (ADMSC-Exo) was designed and fabricated by a physical mixing method to promote the skin full-thickness wound repair. The exosomes were slowly released from the Exo/Gel dressing with the degradation of the chitosan hydrogel. The Exo/Gel displayed enhanced cell migration and angiogenic properties in vitro. And the results in the rat skin wound model showed that the Exo/Gel could promote the regular collagen deposition, angiogenesis, and hair follicle mosaicism regeneration. These results proved that the hydrogel dressing with ADMSCs-derived exosomes can accelerate skin wound healing, which is a strategy for developing wound dressings.

Anticipation and Verification of Dendrobium-Derived Nanovesicles for Skin Wound Healing Targets, Predicated Upon Immune Infiltration and Senescence.

Dendrobium, with profound botanical importance, reveals a rich composition of bioactive compounds, including polysaccharides, flavonoids, alkaloids, and diverse amino acids, holding promise for skin regeneration. However, the precise mechanism remains elusive. Seeking a potent natural remedy for wound healing, exocyst vesicles were successfully isolated from Dendrobium. This investigation aimed to employ bioinformatics and in vivo experiments to elucidate target genes of Dendrobium-derived nanovesicles in skin wound healing, focusing on immune infiltration and senescence characteristics. C57 mice experienced facilitated wound healing through Dendrobium-derived nanovesicles (DDNVs). Bioinformatics analysis and GEO database mining identified crucial genes by intersecting immune-related, senescence-related, and PANoptosis-associated genes. The identified genes underwent in vivo validation. DDNVs remarkably accelerated skin wound healing in C57 mice. Bioinformatics analysis revealed abnormal expression patterns of immune-related, senescence-related, and pan-apoptosis-related genes, highlighting an overexpressed IL-1β and downregulated IL-18 in the model group, Exploration of signaling pathways included IL-17, NF-kappa B, NOD-like receptor, and Toll-like receptor pathways. In vivo experiments confirmed DDNVs' efficacy in suppressing IL-1β expression, enhancing wound healing. Plant-derived nanovesicles (PDNV) emerged as a natural, reliable, and productive approach to wound healing. DDNVs uptake by mouse skin tissues, labeled with a fluorescent dye, led to enhanced wound healing in C57 mice. Notably, IL-1β overexpression in immune cells and genes played a key role. DDNVs intervention effectively suppressed IL-1β expression, accelerating skin wound tissue repair.

Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice

Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice

Enzymatic functionalization of decellularized tilapia skin scaffolds with enhanced skin regeneration.

The decellularized tilapia skin (dTS) has gained significant attention as a promising material for tissue regeneration due to its ability to provide unique structural and functional components that support cell growth, adhesion, and proliferation. However, the clinical application of dTS is limited by its low mechanical strength and rapid biodegradability. Herein, we prepare a novel RGD (arginine-glycine-aspartic acid) functionalized dTS scaffold (dTS/RGD) by using transglutaminase (TGase) crosslinking. The developed dTS/RGD scaffold possesses excellent properties, including a medium porosity of ∼59.2%, a suitable degradation rate of approximately 80% over a period of two weeks, and appropriate mechanical strength with a maximum tensile stress of ∼46.36 MPa which is much higher than that of dTS (∼32.23 MPa). These properties make the dTS/RGD scaffold ideal for promoting cell adhesion and proliferation, thereby accelerating skin wound healing in a full-thickness skin defect model. Such an enzymatic cross-linking strategy provides a favorable microenvironment for wound healing and holds great potential for application in skin regeneration engineering.

Fabrication and evaluation of the regenerative effect of a polycaprolactone/chitosan nanofibrous scaffold containing bentonite nanoparticles in a rat model of deep second-degree burn injury.

In the present study, we evaluated the effect of a nanofibrous scaffold including polycaprolactone (PCL), chitosan (CHT), and bentonite nanoparticles (Ben-NPS) on wound healing in order to introduce a novel dressing for burn wounds. PCL, PCL/CHT, and PCL/CHT/Ben-NPS nanofibrous scaffolds were fabricated by the electrospinning technique. Their structural and physiochemical characteristics were investigated by Fourier-transform infrared spectroscopy (FTIR) analysis, scanning electron microscopy (SEM), tensile strength, water contact angle, as well as, swelling and degradation profiles test. The disc diffusion assay was carried out to investigate the antibacterial potential of the scaffolds. In addition, the cell viability and proliferation ability of human dermal fibroblasts (HDFs) on the scaffolds were assessed using MTT assay as well as SEM imaging. The wound-healing property of the nanofibrous scaffolds was evaluated by histopathological investigations during 3,7, and 14 days in a rat model of burn wounds. SEM showed that all scaffolds had three-dimensional, beadles-integrated structures. Adding Ben-NPS into the PCL/CHT polymeric composite significantly enhanced the mechanical, swelling, and antibacterial properties. HDFs had the most cell viability and proliferation values on the PCL/CHT/Ben-NPS scaffold. Histopathological evaluation in the rat model revealed that dressing animal wounds with the PCL/CHT/Ben-NPS scaffold promotes wound healing. The PCL/CHT/Ben-NPS scaffold has promising regenerative properties for accelerating skin wound healing.

Revitalizing Skin Repair: Unveiling the Healing Power of Livisin, a Natural Peptide Calcium Mimetic.

When the skin is damaged, accelerating the repair of skin trauma and promoting the recovery of tissue function are crucial considerations in clinical treatment. Previously, we isolated and identified an active peptide (livisin) from the skin secretion of the frog Odorrana livida. Livisin exhibited strong protease inhibitory activity, water solubility, and stability, yet its wound-healing properties have not yet been studied. In this study, we assessed the impact of livisin on wound healing and investigated the underlying mechanism contributing to its effect. Our findings revealed livisin effectively stimulated the migration of keratinocytes, with the underlying mechanisms involved the activation of CaSR as a peptide calcium mimetic. This activation resulted in the stimulation of the CaSR/E-cadherin/EGFR/ERK signaling pathways. Moreover, the therapeutic effects of livisin were partially reduced by blocking the CaSR/E-cadherin/EGFR/ERK signaling pathway. The interaction between livisin and CaSR was further investigated by molecular docking. Additionally, studies using a mouse full-thickness wound model demonstrated livisin could accelerate skin wound healing by promoting re-epithelialization and collagen deposition. In conclusion, our study provides experimental evidence supporting the use of livisin in skin wound healing, highlighting its potential as an effective therapeutic option.

Biomedical Potential of Keratin-Biphalin Wound Dressing in Diabetic Mice: In Vitro and In Vivo Studies

ABSTRACTStrategies for successful healing of diabetic wounds are lacking. Natural-derived dressings have gained much attention due to their promising properties. We hypothesized that keratin-biphalin fiber-dressing accelerates skin wound healing in a mouse model of diabetes. Keratin fibers were obtained from mouse fur and soaked in a biphalin solution. Studies on NIH/3T3 cells showed that keratin-biphalin fibers increase cell viability. In vivo studies were made on C57BL/6J mice with iatrogenically induced diabetes. Two full-thickness wounds were created on the back of the mice, one untreated and the other treated with an experimental dressing. Western blot analysis, histopathological and immunohistochemical staining were performed. Biphalin was slowly released from keratin fibers. The obtained keratin-biphalin fibers were biocompatible and supported cell growth. Western blot analysis showed that cells treated with our dressing had an increasing expression level of mTOR, and p-AKT 72 h post-treatment compared to 24 h and 48 h. Animal studies showed that the keratin-biphalin dressing accelerated wound healing on days 5 and 15. Treated wounds showed faster reepithelization and developed thicker epidermis. Histopathological and immunohistochemical studies confirmed that keratin-biphalin fibers stimulate macrophage infiltration, which promotes tissue remodeling and regeneration. Exogenous keratin-biphalin fibers p-AKT/mTOR expression protein in vitro and accelerate skin wound healing in diabetic mice.

A Comprehensive Review on Platelet-Rich Plasma Activation: A Key Player in Accelerating Skin Wound Healing.

Platelet-rich plasma (PRP) activation is emerging as a promising and multifaceted tool for accelerating skin wound healing. This review extensively examines PRP's role in wound healing, focusing on its composition, mechanisms of action, activation methods, and clinical applications. PRP's potential to enhance both chronic and acute wound healing and its applications in cosmetic and aesthetic procedures are explored. Furthermore, this review investigates safety concerns, including adverse reactions, infection risks, and long-term safety implications. Looking to the future, emerging technologies, combination therapies, personalized medicine approaches, and regulatory developments are discussed, pointing towards an important and transformative era in wound healing and regenerative medicine. With its wide-ranging implications for healthcare, PRP activation has the potential to become a ubiquitous and essential therapeutic option, improving patient outcomes and reducing healthcare costs.

Simvastatin-Releasing Nanofibrous Peptide Hydrogels for Accelerated Healing of Diabetic Wounds.

Wound healing is one of the major global health concerns in diabetic patients. Simvastatin (SMV) is a poorly soluble oral cholesterol-lowering drug that may aid diabetic wound healing. In the current study, a thixotropic peptide hydrogel of Fmoc-diphenylalanine (FmocFF) containing SMV was designed to accelerate skin wound healing effectively and safely in diabetic mice. FmocFF hydrogels were prepared at various concentrations by using the solvent-triggering technique and characterized by spectroscopic methods such as attenuated total reflection Fourier transform infrared (FT-IR) spectroscopy and fluorimetry. Mechanical behaviors were explored by oscillatory rheology. In model mice, the regenerative potential of the FmocFF-SMV hydrogel was evaluated in terms of wound contraction and closure, tissue regeneration, acute and chronic inflammation, granulation, and re-epithelization. The results showed that FmocFF-SMV hydrogels had an entangled nanofibrous microstructure and shear-thinning characteristics. FmocFF-SMV demonstrated a sustained drug release over 7 days. Compared to the unloaded FmocFF hydrogel, treatment with FmocFF-SMV led to superior diabetic wound recovery and reduced inflammation. Therefore, the utilization of the sustained-release FmocFF-SMV hydrogel formulation could become an attractive choice for topical wound therapy in diabetes patients.

Paeonol accelerates skin wound healing by regulating macrophage polarization and inflammation in diabetic rats.

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

LB1795 Dual LSD1/HDAC inhibition accelerates skin wound healing

LB1795 Dual LSD1/HDAC inhibition accelerates skin wound healing

Inhibition of CK2α accelerates skin wound healing by promoting endothelial cell proliferation through the Hedgehog signaling pathway.

Diabetes is a chronic disease characterized by perturbed glucose and lipid metabolism, resulting in high blood glucose levels. Many complications induced by endothelial dysfunction can cause disability and even death of diabetic patients. Here, we found that the protein level of casein kinase 2α (CK2α) was increased in the endothelium of mice with type I diabetes (T1D) induced by streptozotocin (STZ) injection. Although a potential correlation between the protein level of CK2α and endothelial dysfunction in diabetes was established, the contribution of CK2α to the progression of endothelial dysfunction in diabetes remained largely unknown. By using CX4945 (a selective CK2α antagonist) and Si-csnk2a1 (small interfering RNA targeting CK2α), we found that inhibition of CK2α accelerated skin wound healing in T1D mice by promoting proliferation of endothelial cells. Administration of CX4945 or Si-csnk2a1 rescued the impaired Hedgehog signaling pathway in high glucose-treated human umbilical vein endothelial cells (HUVECs). Exploration of the underlying molecular mechanism revealed that the protective effect of CK2α inhibition on angiogenesis, which contributes to skin wound healing in diabetic mice, was blocked by administration of GANT61 (an inhibitor targeting the Hedgehog signaling pathway). Our findings establish CK2α as a regulator of endothelial dysfunction in diabetes and demonstrate that inhibition of CK2α accelerates skin wound healing in T1D mice by promoting endothelial cell proliferation via the Hedgehog signaling pathway.

Egg white-derived peptide KPHAEVVLR promotes wound healing in rat palatal mucosa via PI3K/AKT/mTOR pathway

KPHAEVVLR (KR-9) is a peptide derived from egg white hydrolyzed, which has been found to accelerate skin wound healing in mice. However, the effect of KR-9 on wound healing on palatal mucosa in rats remains unknown, and the mechanism through which KR-9 promotes wound healing should be further explored. Herein, we aimed to investigate the effect and mechanism of KR-9 peptide on palatal mucosa wound healing. Our results showed that KR-9 reduced the wound area of palatal mucosa in rats and promoted human gingival fibroblasts(HGFs) migration and proliferation.The peptide can enter into cytoplasm. It also increased the phosphorylation of PI3K, AKT, and mTOR protein. The effect of KR-9 on HGFs migration and proliferation could be reversed by PI3K inhibitor. These results demonstrated that KR-9 peptide facilitated wound healing of palatal mucosa in rats by promoting HGFs migration and proliferation, which was mediated by PI3K/AKT/mTOR signaling pathway. This data proves that KR-9 might be used as a potential agent for wound healing treatment.

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.