Amino acid metabolism serves as a central hub linking retinal energy supply, neurotransmission, and cell signaling, which is critical for maintaining retinal structure and function. This review summarizes the molecular mechanisms by which abnormal amino acid metabolism contributes to retinal diseases. The major mechanisms include: 1) excitotoxicity caused by disruption of glutamate-glutamine cycle; 2) mitochondrial oxidative stress and epigenetic changes due to accumulation of branched-chain and sulfur-containing amino acids; 3) remodeling of immune microenvironment due to altered tryptophan and arginine metabolism; 4) neurotoxic lipid production and signaling imbalance resulting from serine and glycine deficiency. Clinically, we highlight the emerging roles of intraocular fluid metabolomics-based liquid biopsy and artificial intelligence-assisted multimodal imaging in early diagnosis and molecular classification. We further summarize emerging treatment approaches, including metabolic substrate supplementation, interventions targeting key enzymes and transporters, and development of responsive nanodelivery systems. Overall, restoration of amino acid metabolic homeostasis represents a promising strategy for the prevention and treatment of retinal diseases.

In recent years, active monomers derived from Chinese herbal medicine and their derivatives have attracted significant attention in the field of skincare product development. Artemisinin and its derivatives, including dihydroartemisinin (DHA), exhibit diverse pharmacological activities such as anti-inflammatory, antibacterial, immunomodulatory, and antitumor effects, showing promising therapeutic potential in skin-related diseases. However, systematic studies on artemisinins in cosmetics are lacking. This study aimed to evaluate the cosmetic potential of DHA by investigating its anti-aging, anti-hair loss, antibacterial, whitening, and anti-glycation activities. Results showed that DHA exhibits multiple biological activities: DHA exhibits anti-aging activity by promoting collagen I synthesis in HDF cell, exhibits anti-hair loss effect by modulating VEGF and DKK1 expression in DPC cell, exhibits antibacterial activity against Malassezia furfur, exhibits whitening activity by suppressing melanin synthesis, and exhibits anti-glycation activity by suppressing glycation reactions. Overall, with the broad biological activities, we believe that DHA holds encouraging promise in the cosmetics industry.

Parkinson's disease (PD) is closely associated with mitochondrial dysfunction and oxidative stress. Sargassum horneri polyphenols (SHPP), as a marine-derived natural active substance, have potential neuroprotective effects, but their efficacy and mechanisms in PD models remain unclear. In this study, SH-SY5Y cells were first differentiated with all-trans-retinoic acid (ATRA) and then treated with rotenone to establish an in vitro Parkinson's disease injury model. The protective effects of SHPP were systematically evaluated, and its mechanism of action was preliminarily explored using transcriptomics. Results showed that SHPP intervention dose-dependently ameliorated rotenone-induced cell injury: cell viability in the medium- and high-dose groups was restored to 71.6% and 73.3% of the control level, ATP content to 71.2% and 74.6%, and mitochondrial complex I activity to 67.5% and 71.3%, respectively. In the high-dose group, reactive oxygen species (ROS) level decreased to 81.2% of the model group level, malondialdehyde (MDA) decreased to 68.7% of the model group level, and superoxide dismutase (SOD) activity and reduced glutathione (GSH) content was restored to 83.7% and 82.8% of the control level, respectively. In terms of apoptosis regulation, SHPP down-regulated Bax, up-regulated Bcl-2, decreased the Bax/Bcl-2 ratio, and reduced cytoplasmic cytochrome c (by 14.3%) and Cleaved Caspase-3 (by 13.6%) levels. Meanwhile, SHPP reduced the secretion of pro-inflammatory factors TNF-α, IL-6, and IL-1β, and down-regulated BAX mRNA expression while up-regulating BCL2 , NFE2L2 , and HMOX1 mRNA expression. Transcriptomic analysis revealed that only 28 differentially expressed genes were identified after SHPP intervention, of which 8 were common differentially expressed genes between the model and treatment groups (including TMEM102 , MIR34AHG , etc.), indicating that SHPP does not function by broadly altering gene expression but rather acts precisely on core genes in the disease model. In conclusion, SHPP exerts neuroprotective effects against rotenone-induced SH-SY5Y cell injury by restoring mitochondrial function, alleviating oxidative stress, inhibiting mitochondria-mediated apoptosis, and reducing neuroinflammation, providing experimental evidence for the potential application of S. horneri polyphenols in the prevention and treatment of Parkinson's disease.

Our previous genome-wide screening has linked THSD7A (thrombospondin type 1 domain containing 7A) gene to human coronary artery disease (CAD). How THSD7A contributes to atherosclerosis, however, remains unclear. In this study, we show THSD7A is increased in human carotid arteries and mouse atherosclerotic plaques. In apolipoprotein E knockout (ApoE-/-) mice, the overexpression of THSD7A increases monocyte-endothelial adhesion and macrophage infiltration, exacerbating atherosclerotic lesions, whereas Thsd7A knockout (Thsd7A-/-) attenuates these phenotypic changes. Integrated single-cell and bulk transcriptomic profiles demonstrate that THSD7A activates IL1A (Interleukin 1 alpha) signaling, augmenting endothelial inflammation. Mechanistically, THSD7A binds to integrin αvβ3, and such binding activates ERK (Extracellular signal-regulated kinase) and augments IL1A-associated proinflammatory signaling. Notably, IL1A serves as a transcriptional target of CEBPD (CCAAT/enhancer-binding protein delta), and CEBPD knockdown rescues THSD7A-mediated endothelial inflammation. These findings establish THSD7A as a novel and critical mediator in the regulation of the αvβ3/CEBPD/IL1A axis that controls endothelial inflammatory responses associated with atherosclerosis and demonstrate the importance of CEBPD as a downstream molecule in mediating THSD7A-associated signaling. This study positions THSD7A as both a genetic marker and a potential therapeutic target.

Ulva prolifera (U. prolifera), a large green alga widely distributed along coastlines worldwide, can trigger marine ecological issues such as “green tides” when over-proliferating. Nevertheless, it is abundant in various nutrients and bioactive compounds, making the utilization of this alga an urgent task. In this study, an antioxidant peptide fraction (UCP‑1) was isolated and purified from U. prolifera. LC‑MS/MS analysis indicated that the peptide composition and molecular weight distribution of UCP‑1 possess typical characteristics of antioxidant peptides. In vitro experiments demonstrated that UCP‑1 at a concentration of 1 mg mL⁻¹ exhibited a DPPH radical scavenging capacity of 38.86 ± 2.7

Background: Obesity is a heterogeneous chronic disease driven by interacting genetic, metabolic, inflammatory, and environmental factors, yet clinically useful blood-based markers for early risk stratification remain limited. Methods: Using plasma proteomic data from the UK Biobank, we assessed 2,923 circulating proteins in relation to incident obesity. Findings: We identified 98 proteins associated with future risk, with changes detectable years before clinical onset. These proteins were enriched in pathways related to metabolism, low-grade inflammation, and tissue remodeling and were linked to diverse systemic phenotypes. A protein-based model achieved an AUC of 0.809 for predicting incident obesity. Integrative analyses highlighted ADM, NCAN, APOM, and LEP as key candidates, suggesting distinct biological contributions to obesity development. Interpretation: Collectively, these findings delineate early circulating proteomic alterations preceding obesity and support their potential utility for risk prediction and mechanistic prioritization.

ABSTRACT Retinal neurodegeneration leads to progressive and irreversible vision loss driven by retinal ganglion cell (RGC) death, yet effective neuroprotective therapies remain lacking. Recent studies suggest that small non‐coding RNAs play key roles in central nervous system injury, but their relevance to retinal neurodegeneration remains incompletely understood. Here, we identify a significant increase in 5ʹtiRNA‐His‐GTG, an ANG‐generated tRNA‐derived fragment, in mouse models of retinal neurodegeneration. Functionally, elevated 5ʹtiRNA‐His‐GTG promotes reactive gliosis and contributes to RGC degeneration through Müller cell‐RGC crosstalk. Conversely, inhibition of 5ʹtiRNA‐His‐GTG attenuates glial activation, preserves RGC survival, and improves visual function and vision‐dependent behaviors. Mechanistically, 5ʹtiRNA‐His‐GTG induces neurodegenerative changes by suppressing the LPCAT1‐mediated phosphatidylcholine (PC) biosynthetic pathway and perturbing glycerophospholipid metabolism. Notably, restoration of LPCAT1 expression or PC levels reverses 5ʹtiRNA‐His‐GTG‐induced neurodegeneration both in vitro and in vivo. These findings uncover a previously unrecognized 5ʹtiRNA‐His‐GTG‐LPCAT1‐PC regulatory pathway that contributes to retinal neurodegeneration. Collectively, our study identifies 5ʹtiRNA‐His‐GTG as a critical mediator of glial‐driven neuroinflammation and neuronal loss, and highlights this signaling axis as a potential therapeutic target for retinal neurodegeneration.

Skin photoaging is primarily induced by ultraviolet (UV) radiation and is accompanied by extracellular matrix (ECM) degradation, abnormal pigmentation, and loss of skin elasticity. Excessive melanin synthesis represents a key cause of pigmentary skin disorders. Natural polyphenols with dual skin-whitening and anti-photoaging activities have attracted increasing attention as cosmetic ingredients. This study examined the effects of polyphenol-enriched fraction from the brown alga Sargassum fusiforme (SFP). Zebrafish embryos and human melanoma A375 cells were used to evaluate the depigmenting efficacy of SFP, while UVA-induced human dermal fibroblasts (HDFs) were employed to assess its anti-photoaging activity. SFP significantly decreased melanin levels in both models in a dose-dependent and reversible manner by suppressing tyrosinase activity. In terms of anti-photoaging effects, SFP markedly suppressed UVA-induced matrix metalloproteinases (MMPs) expression and elevated key ECM components, including type I collagen, elastin, and hyaluronic acid. In conclusion, SFP exerts dual beneficial effects by attenuating melanogenesis via tyrosinase inhibition and alleviating photoaging damage by suppressing MMPs to protect ECM. These results provide a scientific foundation for the use of SFP as a dual-purpose natural cosmetic ingredient with significant potential in the cosmetics sector.

Endothelial cells are critical in the regulation of blood pressure. We previously demonstrated AGGF1 was crucial for maintaining endothelial cell function. This study aims to examine whether AGGF1 regulates blood pressure. Here, we found that AGGF1 expression was inversely correlated with blood pressure with age. In male mice, endothelial-specific loss of function of Aggf1 (Aggf1flox/flox/Tie2-Cre+) significantly increased blood pressure, whereas endothelial-specific human AGGF1 overexpression (TGM(Tie2-hAGGF1)) suppressed age-elevated blood pressure. The endothelial-specific loss of AGGF1 accelerated early vascular aging, characterized by increased arterial stiffness, impaired endothelium-dependent vasorelaxation, reduced eNOS phosphorylation, and augmented ROS production, whereas AGGF1 overexpression rescued these phenotypic changes. Mechanistically, we found that nuclear-localized AGGF1 bound to the SESN2 promoter and enhanced its transcription. This upregulation of SESN2 attenuated mitochondrial dysfunction, including respiratory dysfunction and elevated mitochondrial ROS, and ultimately led to increased p-eNOS levels and improved endothelial function. Furthermore, SESN2 overexpression rescued early vascular aging and reduced blood pressure in Aggf1flox/flox/Tie2-Cre+ mice, while SESN2 knockdown attenuated the beneficial vascular effects of AGGF1. Together, we demonstrate that endothelial AGGF1/SESN2/p-eNOS is a novel and important signaling axis in the maintenance of blood pressure. Age suppresses the AGGF1/SESN2/p-eNOS signaling cascade, leading to an elevation of blood pressure. Our study provides new insights into age-elevated blood pressure in male mice and suggests AGGF1 as a potentially valuable target for prehypertension intervention in the elderly male population.

Pericyte loss is an early and critical event in the pathogenesis of diabetic retinopathy (DR), yet the molecular mech-anisms underlying pericyte dysfunction remain incompletely understood. Using single-cell RNA sequencing, we generated a retinal cellular overview comprising 37,982 cells from diabetic and nondiabetic mice. We identified a previously unrecognized pericyte subpopulation defined by high expression of pituitary tumor-transforming gene 1 (Pttg1), which was enriched in diabetic retina. Functional studies demonstrated that CRISPR-Cas9- or small interfering RNA-mediated silencing of PTTG1 restored pericyte stability and barrier- supporting function under high-glucose stress. In vivo, Pttg1 silencing via viral or pericyte- specific adeno- associated virus delivery improved retinal vascular integrity and reduced retinal vascular dysfunction in diabetic mice. Integrated transcriptomic and metabolomic profiling revealed that PTTG1 silencing reprogrammed metabolism, modulating glycolytic flux and attenuating oxidative stress. Furthermore, a therapeutic strategy using spherical nucleic acid-based siPttg1 nano-carriers (sTDN- siPttg1) substantially ameliorated retinal vascular dysfunction in DR model. These findings suggest that PTTG1 is a critical regulator of pericyte metabolic homeostasis and microvascular function in DR, highlighting its translational potential as a therapeutic target for diabetic microvascular complications.

Background: As the body’s first line of defense against environmental stressors, the skin is highly susceptible to UVB-induced damage, which triggers inflammation and impairs barrier function. This study investigates the protective effects of safflower seed oil (SSO) and fermented Artemisia annua oil (FAAO) against UVB-induced skin injury. Methods: The protective effects of SSO and FAO against UVB irradiation was first tested in HaCaT keratinocyte. Subsequently, a UVB-irradiated SKH-1 mouse model was established to evaluate these two oils. RNA-seq analysis was employed to investigate the potential molecular mechanisms by which SSO and FAO repair the skin barrier. Results: In vitro experiments demonstrated that SSO (0.25%) and FAAO (0.1%) significantly enhanced HaCaT keratinocyte viability following UVB exposure while selectively modulating pro-inflammatory cytokine production. In a UVB-irradiated SKH-1 mouse model, standalone SSO or FAAO treatment partially ameliorated epidermal hyperplasia and restored UV-reduced collagen content, while the 1:1 SSO/FAAO combination exhibited superior efficacy in restoring skin architecture, reducing erythema and edema, and suppressing immune cell infiltration. Transcriptomic profiling revealed that the combined treatment promoted structural repair by attenuating inflammatory responses and preserving extracellular matrix homeostasis. Conclusions: Together, these findings underscore the potential of SSO/FAAO as a multifunctional botanical intervention for mitigating UVB-induced cutaneous damage.

This study aimed to evaluate the independent and joint effects of adherence to healthy dietary patterns and slower biological aging on the incidence of diabetic microvascular complications in individuals with type 2 diabetes mellitus (T2DM), and to assess the mediating role of biological aging. In a prospective cohort of 13,294 T2DM participants without baseline DMCs, dietary quality was assessed using a validated 10-point score, while biological aging was calculated from nine biomarkers and chronological age. Cox regression models were used to assess associations, and mediation analysis was performed to estimate the mediating effects of biological aging. Over a mean follow-up of 11.9 years, 3197 participants developed DMCs, including 1392 cases of diabetic retinopathy (DR), 1908 of diabetic nephropathy (DN), and 598 of diabetic neuropathy (DPN). Higher dietary scores (6–10) were associated with reduced risks of composite DMCs (HR 0.845; 95

In our daily life, our skin is frequently exposed to water, which can affect human health. Previous studies have demonstrated that water bathing improves skin conditions in individuals with dermatoses. However, whether groundwater bathing influences epidermal gene expression in normal skin is largely unknown. Therefore, we compared epidermal gene expression in mice exposed in groundwater and deionized water. Flank of mouse skin was exposed to either groundwater or deionized water for 30 min twice daily for three consecutive days. Expression levels of epidermal mRNA were compared between the skin exposed to deionized and groundwaters. In comparison to deionized water, spring water A (Yichun) upregulated 257 genes and downregulated 380 genes, while spring water B (AVENE) upregulated 242 genes and downregulated 668 genes. Moreover, spring water A upregulated 469 genes and downregulated 277 genes compared to spring water B. Spring water A downregulated genes were mainly enriched in the pathways associated with keratinization, keratinocyte differentiation and development, while upregulated genes were enriched in the pathways associated with muscle contraction, sarcomere organization and skeletal muscle fiber development. Whereas genes upregulated by spring water B were associated with pathways related to ion transport and activation of endothelial cells, while downregulated genes were related to keratinization, response to bacteria and keratinocyte differentiation. Collectively, groundwater can affect epidermal gene expression. The influences of water bathing on epidermal gene expression vary with water, likely due to the differences in active constitutes in the water. However, the clinical significance of altered epidermal gene expression remains to be explored.

Vascular aging contributes to the morbidity and mortality in older individuals, closely linked to an imbalance between energy consumption and production. Despite its importance, our understanding of how aging affects vascular metabolism and leads to vascular diseases remains limited. In this study, we explored the metabolomic characteristics of vascular aging by analyzing aortic tissues from young and old mice through untargeted metabolomic analysis using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLCMS/MS). We identified 85 differential metabolites, with 37 up-regulated and 48 down-regulated, primarily consisting of lipids and lipid-like molecules, based on the criteria of variable importance in projection (VIP) > 1 and P < 0.05. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant involvement of these metabolites in six metabolic pathways (P < 0.05), particularly in glycerophospholipid metabolism. Receiver operating characteristic (ROC) curve analysis highlighted eight altered metabolites in glycerophospholipid metabolism, such as phosphatidylcholine (PC) (17:0/22:6) and lysophosphatidylcholine (LPC) (18:2), which demonstrated strong discriminatory ability for vascular aging with an area under the curve (AUC) exceeding 0.85. This study provides novel insights into metabolomic signature of vascular aging, offering important clues for future treatments of age-related vascular disorders.

Background: Atherosclerosis is the pathological basis for lethal cardio-cerebral vascular diseases, such as coronary artery disease and stroke. Fructus Choerospondiatis (FC) has demonstrated cardiac protective effects in multiple ethnomedicine. Whether these protective effects are attributed to the prevention of vascular atherosclerosis, however, remains unknown. We aim to examine the anti-atherosclerotic effect of FC aqueous extract and elucidate the underlying mechanism. Methods: FC was separated into peel and pulp, and the aqueous extract was obtained separately by boiling in water to mimic decocting. Atherosclerosis model was established in ApoE-/- mice fed with a high-fat diet, and histological analysis were utilized to evaluate the development of atherosclerosis. Various inflammatory models were constructed in mice to evaluate the anti-inflammatory effect of FC extract systemically, including acute local inflammation induced by traumatic injury (ear/foot swelling), acute systemic inflammation triggered by pathogenic infection (LPS- and POLY (I:C)-induced), as well as chronic inflammatory conditions associated with oxidative stress (D-galactose-induced), metabolic disorder (db/db mice), and aging. LC-MS and network pharmacology identified bioactive components and targets. Western blotting, ELISA, qPCR, and immunofluorescence were utilized to analyze the key genes involved in the mechanisms. Results: FC peel extract reduced serum IL-6 level, atherosclerotic plaque area, and macrophage content in the plaque, while pulp extract showed no protective effects. Peel extract exhibits anti-inflammatory effects in all models. The integrative application of LC-MS and network pharmacology identified ellagic acid as the major bioactive component and AKT as its target protein. Mechanistically, FC peel extract inhibits AKT phosphorylation, suppresses c-FOS expression and nuclear translocation, reduces IL-6 transcription and inflammation, and thus alleviates atherosclerosis. Conclusions: FC peel aqueous extract exerts anti-atherosclerotic effect by inhibiting inflammation through AKT/c-FOS/IL-6 axis. This study provides novel insights into the protective effects against atherosclerosis of FC peel and highlights its potential application in the prevention and treatment of coronary artery diseases.

Although RNASEK is defined as a subunit of V-ATPase, how it regulates the V-ATPase and relevant physiological functions remains largely uncharacterized. Utilizing a homozygous RNASEK knockout mouse, we demonstrate that the null function of RNASEK leads to catastrophic developmental failure at the egg cylinder stage (E5.5). Rnasek-/- embryos exhibit pronounced lysosomal dysfunction and multilineage proliferation arrest, accompanied by the hallmarks of senescence, including elevated p21, reduced Ki67 and EdU incorporation as well as increased γH2AX foci, which are evident in vitro embryo culture as well. Unexpectedly, despite increased V0/V1 subunit colocalization, lysosomal alkalization, proteolytic failure, and autophagic flux blockade collectively indicate that the loss of RNASEK promotes malfunctional V-ATPase assembly. Pharmacological restoration of lysosomal acidity via EN6 partially mitigates senescence and extends the developmental window. These findings demonstrate that RNASEK regulates lysosomal function via V-ATPase and is required for egg cylinder development in the mouse embryo. Loss of RNASEK promotes premature senescence of multiple cell lineages, terminating early embryonic development.

AIMS:This study aims to identify potential therapeutic targets for diabetic microangiopathy by integrating genome-wide association studies (GWAS) and Mendelian randomization (MR) analyses. METHODS:A comprehensive analysis of GWAS datasets on diabetic microangiopathy was conducted by using two-sample MR to determine the causal effects of blood-expressed druggable genes at both the transcriptional and protein levels. Co-localization analysis was conducted to validate gene-trait associations, while phenome-wide association studies (PheWAS) explored broader phenotypic implications. Additionally, protein-protein interaction (PPI) networks were constructed to elucidate gene interactions and molecular docking was conducted to determine therapeutic druggability. RESULTS:Nine candidate therapeutic targets (PSORS1C3, HLA-C, RAMP1, CTSG, SREBF1, BTN3A2, PPA1, PRKD2, and PPIG) were identified, with co-localization analysis confirming their involvement in diabetic microangiopathy. Among them, HLA-C exhibited associations with additional traits, suggesting the specificity of the remaining targets. Functional enrichment analysis indicated a predominant involvement of immune-related pathways, underscoring their relevance to the pathogenesis of diabetic microangiopathy. Furthermore, molecular docking studies revealed strong binding affinities. CONCLUSIONS:This study provides compelling genetic evidence supporting the role of immune-related druggable genes in diabetic microangiopathy and identifies novel therapeutic targets for intervention.

Vascular aging increases the susceptibility to cardio-cerebrovascular conditions, such as atherosclerotic diseases and hypertension, the leading causes of global disability and mortality. Dietary citrate extends the lifespan of Drosophila melanogaster and Caenorhabditis elegans as well as improves the memory of mice injured by a high-fat diet (HFD); whether it alleviates vascular aging and age-related vascular diseases; however, remains unknown. Here, we showed that dietary supplementation of citrate delayed vascular aging, as evidenced by maintaining the integrity of elastic fibers and decreasing the level of the aging-related marker, CDKN1A (p21). Functionally, citrate improved the sensitivity to endothelial-dependent vasodilators and lowered blood pressure, and in HFD-fed ApoE-/- mice, it reduced the size of atherosclerotic plaques, decreased the necrotic core area and vulnerability index in aortic root plaques. Additionally, citrate decreased the frailty index, increased bone density, and improved maximal grip strength and balance speed in both aged and HFD-fed ApoE-/- mice. Mechanistically, we showed that citrate exposure delayed human umbilical vein endothelial cell senescence with a decreased percentage of cells stained with senescence-associated β-galactosidase and p21 levels. Moreover, citrate activated AMPK-related pathways and reversed senescence-related mitochondrial dysfunction in basal respiration, maximal respiration, and ATP production and reduced the production of reactive oxygen species (ROS). The citrate-promoted beneficial effects were abolished due to inactivated AMPK and the increased mitochondrial ROS. Thus, we demonstrate that dietary citrate delays vascular aging and alleviates age-related vascular diseases by improving mitochondrial function via activation of AMPK-related pathways. Citrate may have potential clinical implications for interventions against vascular aging and age-related vascular diseases.

Diabetic retinopathy (DR) is a leading cause of vision loss characterized by concurrent retinal vascular dysfunction and neurodegeneration. While current therapies primarily target vascular dysfunction, they offer limited neuroprotective benefits. In this study, we developed a novel light-responsive hydrogel composed of hyaluronic acid methacryloyl (HAMA) for the co-delivery of aflibercept and miR-21-3p antagomir (HAMA@(Ab+M21A)). This dual-therapeutic strategy was designed to concurrently target retinal vascular dysfunction and neurodegeneration. Upon light exposure, HAMA hydrogel undergoes rapid in situ crosslinking, exhibiting excellent ocular biocompatibility and sustained drug release over 45 days, in parallel with controlled biodegradation. HAMA@(Ab+M21A) effectively inhibits VEGF-induced vascular dysfunction, suppresses reactive gliosis, and promotes retinal ganglion cell survival in vitro and in vivo. Collectively, this study demonstrates the therapeutic potential of HAMA@(Ab+M21A) as a dual-function strategy for DR, providing both anti-angiogenic and neuroprotective effects to impede disease progression.

Ethnopharmacological relevance: Artemisia annua L. belongs to the Asteraceae family and has a long history of clinical application in China. It has been widely used for centuries to treat fever, malaria, jaundice and some skin diseases (such as scabies and sores). Modern pharmacological studies have shown that it has anti-inflammatory, immunomodulatory, antimalarial and antibacterial effects. Aim of study: This study aimed to investigate the anti-eczema effect of A. annua aqueous extract (AAE), profile its potential bioactive components and try to explore its possible underlying mechanisms. Materials and methods: The MTT assay was employed to assess the cytotoxicity of AAE. The anti-eczema effect of AAE was evaluated using both an in vitro 3D epidermal inflammation model and an in vivo guinea pig itching model. The bioactive components of AAE were characterized by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry coupled with the UNIFI platform. Results: In this study, we found that AAE is safe for primary human skin keratinocytes at concentrations ranging from 31.3 mu g/mL to 250 mu g/mL. Further investigations indicate that AAE can increase the itching threshold, inhibit the expression of the inflammatory cytokine TSLP, and promote the expression of FLG mRNA. Additionally, the utilization of UPLC-QTOF/MS and UNIFI platform enabled us to identify 61 potential bioactive components of AAE, with sesquiterpenes and phenolic acids being the most abundant components. Conclusions: In this study, the anti-inflammatory and anti-itch effects of the A. annua extract were revealed, along with sesquiterpenes and phenolic acids were identified as potential bioactive components according to literature. The AAE extract holds potential for utilization in the treatment of eczema.